Registered study purpose

“This is a single arm Phase 2 trial to evaluate the efficacy and safety of RP-A501, a recombinant adeno-associated virus serotype 9 (rAAV9) vector containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene, in male patients with Danon disease.” (opens the source at this quote in a new tab)
“The study is designed to assess the efficacy and safety of a single intravenous dose of RP-A501 in treating the cardiomyopathy associated with Danon disease.” (opens the source at this quote in a new tab)

Primary objective in the European Union trial record

“The primary objective of this study is to evaluate whether RP-A501 (an AAV9 capsid containing the LAMP2B transgene; AAV9.LAMP2B) will result in significant improvement as assessed via the primary endpoint comprised of LAMP2 myocardial tissue expression and LVMI.” (opens the source at this quote in a new tab)

Secondary objectives in the European Union trial record

“To assess the impact of RP-A501 on the components of the primary endpoint” (opens the source at this quote in a new tab)
“To assess the impact of RP-A501 on biomarker evidence of myocardial injury” (opens the source at this quote in a new tab)
“To assess the impact of RP-A501 on quality of life and heart failure symptoms” (opens the source at this quote in a new tab)
“To assess the impact of RP-A501 on event-free survival” (opens the source at this quote in a new tab)
“To assess the impact of RP-A501 on safety” (opens the source at this quote in a new tab)

Regulatory purpose stated by the sponsor: support for an accelerated approval application (October 2026)

“FDA agreement to complete Cohort 4 supporting BLA submission for accelerated approval; PRV eligible” (opens the source at this quote in a new tab)
“Clear path to BLA submission to support accelerated approval” (opens the source at this quote in a new tab)

Study dates and status in the registry (record updated October 6, 2026)

Field	Registry record
Recruitment status	“Recruiting”
Study start (actual)	“2023-09-05”
Primary completion (estimated)	“2028-06”
Study completion (estimated)	“2032-06”
First posted	“2023-10-23”
Last update posted	“2026-10-06”

Registered sites: 6 locations in 4 countries

“This study has 6 locations” (opens the source at this quote in a new tab)

Country	Site	City
United States	“University of California, San Diego”	“La Jolla, California, United States, 92037”
United States	“Boston Children's Hospital”	“Boston, Massachusetts, United States, 02115”
United States	“Children's Hospital of Philadelphia”	“Philadelphia, Pennsylvania, United States, 19104”
Germany	“German Heart Center Munich”	“Munich, Germany”
Italy	“Meyer Children's Hospital”	“Florence, Italy”
United Kingdom	“Great Ormond Street Hospital & UCL Institute of Cardiovascular Science”	“London, United Kingdom”

Principal investigators in the registry

Role	Name	Affiliation
Principal investigator	“Joseph Rossano, MD”	“Children's Hospital of Philadelphia”
Principal investigator	“Barry Greenberg, MD”	“University of California, San Diego”

European Union member states: authorisation decision dates and recruitment status

Member state	Current status	Decision date
Germany	“Ongoing, recruiting”	“19/01/2024”
Italy	“Ongoing, recruiting”	“28/08/2024”
Spain	“Authorised, recruitment pending”	“31/08/2026”

European Union trial sites, including a site in Spain that the ClinicalTrials.gov record does not list

“Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen” (opens the source at this quote in a new tab)
“Azienda Ospedaliera Universitaria Meyer IRCCS” (opens the source at this quote in a new tab)
“Hospital Sant Joan De Deu Barcelona” (opens the source at this quote in a new tab)

European Union record: temporary halt on May 25, 2025, and restart on February 26, 2026, in Germany and Italy

Event	European Union record
Temporary halt (Germany and Italy)	“25/05/2025”
Restart (Germany and Italy)	“26/02/2026”
Temporary halt notifications	“Temporary Halt (2)”

Estimated end of trial: October 2029 in the European Union record and June 2032 on ClinicalTrials.gov

Field	European Union record
Estimated recruitment start date in the EU/EEA	“01/04/2024”
Estimated end of trial date in the EU/EEA	“31/10/2029”

Field	Registry record
Study completion (estimated)	“2032-06”

Sponsor timeline as of October 6, 2026: dosing completion, topline readout, and application filing

Milestone	Timing as printed	Description
Enrollment and dosing	“TODAY”	“9 additional patients in Cohort 4”
Dosing completion	“MID-2027”	“Last patient dosed”
Topline readout	“MID-2028”	“Primary efficacy readout from pivotal Cohort 4”
Regulatory filing	“LATE-2028”	“BLA regulatory filing”

“MID-2028 target is provisional pending alignment with dosing completion and 12-month follow-up.” (opens the source at this quote in a new tab)

“Rocket expects to complete pivotal trial dosing by mid-2027, with topline results anticipated mid-2028.” (opens the source at this quote in a new tab)

History: European Union authorisation in January 2024 and completion of enrollment in September 2024

“In January 2024, we received CTIS approval to include clinical trial sites in certain EU Member States.” (opens the source at this quote in a new tab)
“In September 2024, we announced completion of enrollment of 12 patients in the Phase 2 study across sites in the U.S. and EU.” (opens the source at this quote in a new tab)

History: dosing halted on May 7, 2025, and FDA clinical hold from May 23, 2025, to August 2025

“Per protocol, study enrollment was suspended and planned treatment of any new subjects with RP-A501 was halted on 07-May-2025.” (opens the source at this quote in a new tab)

“Rocket voluntarily paused further Phase 2 study dosing in the U.S. and EU, and the FDA subsequently placed the trial on clinical hold on May 23, 2025 to allow for further evaluation.” (opens the source at this quote in a new tab)

“today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the Company’s pivotal Phase 2 trial of RP-A501 for the treatment of Danon disease” (opens the source at this quote in a new tab)
“The hold was lifted in under three months” (opens the source at this quote in a new tab)

History: dosing reinitiated under the modified protocol by May 2026

“Pivotal Phase 2 trial of RP-A501 for Danon disease progressing with dosing reinitiated” (opens the source at this quote in a new tab)
“Dosing the initial three-patient cohort for the Phase 2 study of RP-A501 in Danon disease is on track.” (opens the source at this quote in a new tab)

Single-arm, open-label, single-dose design in the registry

“RP-A501-0123 is a Phase 2 global, multi-center, single arm, open-label, single dose trial in males with Danon disease.” (opens the source at this quote in a new tab)
“The trial will include a total of 5 years of follow-up after administration of RP-A501.” (opens the source at this quote in a new tab)

Registry design fields

Field	Registry record
Phase	“Phase 2”
Primary purpose	“Treatment”
Allocation	“N/A”
Interventional model	“Single Group Assignment”
Masking	“None (Open Label)”

Four cohorts in the registry (record updated October 6, 2026)

“Cohort 1: Adolescent/Adult males (age ≥ 15 years) [N=1 subject; enrollment closed]” (opens the source at this quote in a new tab)
“Cohort 2: Pediatric males (age 8 to 14 years) [N= 3 subjects; enrollment closed]” (opens the source at this quote in a new tab)
“Cohort 3: Males age ≥ 8 years receiving a pegcetacoplan-containing immunomodulatory regimen [N=2 subjects; enrollment closed]” (opens the source at this quote in a new tab)
“Cohort 4: Males age ≥ 8 years [N=12 subjects; enrolling]” (opens the source at this quote in a new tab)

Pivotal cohort as described by the sponsor in October 2026

“Pivotal, global, single-arm, open-label trial” (opens the source at this quote in a new tab)
“Cohort 1-3 completed” (opens the source at this quote in a new tab)
“Pivotal data package: 12 patients at recalibrated dose + revised immunomodulatory regimen (Cohort 4)” (opens the source at this quote in a new tab)
“FDA agreement obtained to support completion of pivotal study” (opens the source at this quote in a new tab)

FDA alignment on the design elements of the pivotal cohort (September 2026)

“today announced alignment with the U.S. Food and Drug Administration (FDA) on continued enrollment and dosing and key elements of the global pivotal Phase 2 trial of RP-A501 for the treatment of Danon disease, including the recalibrated dose, 12-patient pivotal population and established 12-month co-primary endpoints” (opens the source at this quote in a new tab)
“Following its review of the available safety data, the FDA confirmed continued enrollment and dosing under the modified protocol at the recalibrated dose.” (opens the source at this quote in a new tab)

Sequential dosing of the first three participants of cohort 4

“The FDA authorized the pivotal study to resume first with a recalibrated dose of 3.8 x 10¹³ GC/kg of RP-A501 in three patients, treated sequentially with a minimum four-week interval between each treatment.” (opens the source at this quote in a new tab)

“Dosing proceeded sequentially, with at least four weeks between infusions.” (opens the source at this quote in a new tab)

External comparator: concurrent natural history study

“A global natural history study will serve as an external comparator and run concurrently to the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

“A global natural history study is also running concurrently to the Phase 2 pivotal trial and will serve as an external comparator.” (opens the source at this quote in a new tab)

“A global natural history study is also running concurrently with the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

External comparator: design elements presented in September 2023

“Entry criteria and endpoints similar to Phase 2 trial” (opens the source at this quote in a new tab)
“Appropriate matching to ensure robust comparisons” (opens the source at this quote in a new tab)
“Retrospective data collection to supplement prospective evaluation to ensure sufficient comparative data” (opens the source at this quote in a new tab)
“Each patient’s baseline AND matched external comparator arm together provide robust control data to assess treatment effect” (opens the source at this quote in a new tab)
“External comparator arm serves as control at each timepoint” (opens the source at this quote in a new tab)

Rationale for a single-arm design: FDA position reported by the sponsor in December 2022

“we anticipate utilizing a single arm open-label trial design with a robust natural history comparator, pursuant to the FDA’s acknowledgment of the challenges associated with executing a randomized controlled trial in Danon Disease” (opens the source at this quote in a new tab)

Three-month observational run-in before treatment

“All patients enrolled in the trial are required to have a three-months observational pre-treatment run-in to enable an assessment of troponin (and other biomarker) trajectories to optimally assess this key secondary endpoint.” (opens the source at this quote in a new tab)

Central, blinded reading of echocardiograms

“All measurements of cardiac structure and function (LVEF, LV Mass, LVMI, IVSd and LVPWd) utilized centrally evaluated echocardiogram data (blinded review) for all participants.” (opens the source at this quote in a new tab)

Independent data safety monitoring committee

“IDSMC: expertise in adult and pediatric cardiomyopathy, immunology, and biostatistics” (opens the source at this quote in a new tab)

“Rocket is working with the FDA, the Independent Data Safety Monitoring Committee, clinical investigators, and scientific experts, and is committed to ensuring the safety of all study patients while resuming the trial as expeditiously as possible.” (opens the source at this quote in a new tab)

Participant procedures described on the recruitment site

“This will occur at the study site and includes ECHO, EKG, cardiac MRI, heart biopsy” (opens the source at this quote in a new tab)
“You will be hospitalized for gene therapy treatment and for safety monitoring which will continue as an outpatient.” (opens the source at this quote in a new tab)
“You will return to the clinical site for ongoing monitoring over the course of 5 years.” (opens the source at this quote in a new tab)

History: design aligned with the FDA in September 2023 (12 participants at 6.7 × 10¹³ GC/kg with a pediatric safety run-in)

“Final alignment reached on a single arm, open-label study with natural history comparator and a biomarker based co-primary endpoint consisting of LAMP2 protein expression and Left Ventricular (LV) Mass” (opens the source at this quote in a new tab)
“The global, single-arm, multi-center Phase 2 pivotal trial will evaluate the efficacy and safety of RP-A501 in 12 patients with Danon Disease, including a pediatric safety run-in (n=2), with a natural history comparator and a dose level of 6.7 x 1013 GC/kg.” (opens the source at this quote in a new tab)

“Initial n=2 peds followed for 90 days for key AAV-associated toxicities prior to subsequent ped pt enrollment” (opens the source at this quote in a new tab)
“Pivotal, global, single-arm, open label study with external comparator” (opens the source at this quote in a new tab)

History: pediatric safety run-in as conducted

“The pediatric run-in enrolled two patients in a sequential manner with a minimum three-month follow-up prior to subsequent enrollment.” (opens the source at this quote in a new tab)

History: design changes authorized when the clinical hold was lifted in August 2025

“The trial began with a pediatric safety run-in (n=2) and treated a total of six patients at a dose level of 6.7 x 1013 GC/kg.” (opens the source at this quote in a new tab)
“Per alignment with the FDA upon lifting of the clinical hold, three additional patients are expected to be treated at a dose level of 3.8 x 1013 GC/kg with a minimum four-week interval between dosing, followed by additional patients to complete the trial.” (opens the source at this quote in a new tab)

History: design status reported in August 2026, before FDA alignment on the pivotal population

“The pivotal Phase 2 trial was designed as a 12-patient, single-arm study.” (opens the source at this quote in a new tab)
“The Company is actively engaging with the FDA to align on the path to dosing additional patients and completing the trial and expects to provide an update on the regulatory pathway in the second half of 2026.” (opens the source at this quote in a new tab)

Key inclusion criteria in the registry

“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.” (opens the source at this quote in a new tab)
“Male.” (opens the source at this quote in a new tab)
“Age ≥8 years.” (opens the source at this quote in a new tab)
“Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following:” (opens the source at this quote in a new tab)
“Abnormal thickening of left ventricular wall,” (opens the source at this quote in a new tab)
“Left ventricular ejection fraction (LVEF) ≥ 50%.” (opens the source at this quote in a new tab)
“New York Heart Association (NYHA) Class II to III.” (opens the source at this quote in a new tab)
“High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (ULN) ≤ 12 months prior to screening.” (opens the source at this quote in a new tab)
“Ability to comply with study procedures including investigational therapy and follow-up evaluations.” (opens the source at this quote in a new tab)

Key exclusion criteria in the registry

“Anti-AAV9 neutralizing antibody titer >1:40.” (opens the source at this quote in a new tab)
“Severe heart failure or requirement for advanced therapies (requirement for intravenous inotropic, vasodilator, or diuretic therapy within the 30 days prior to enrollment, presence or requirement for mechanical circulatory support (MCS), and presence or requirement for mechanical ventilation).” (opens the source at this quote in a new tab)
“History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.” (opens the source at this quote in a new tab)
“Prior cardiac or other organ (lung, liver, other) transplantation.” (opens the source at this quote in a new tab)

Age, sex, and healthy volunteer fields in the registry

Field	Registry record
Ages eligible for study	“8 Years and older”
Sexes eligible for study	“Male”
Accepts healthy volunteers	“No”

Wall thickness thresholds that define left ventricular hypertrophy in the European Union record

“Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following: a. For subjects < 18 years, z-score of the left ventricular posterior wall or interventricular septum at end diastole ≥+ 2, and for subjects ≥18 years, left ventricular posterior wall or interventricular septum at end diastole >13 mm (>12 mm if family history of clinically significant Danon disease), b. Left ventricular ejection fraction (LVEF) ≥ 50%.” (opens the source at this quote in a new tab)

Inclusion criterion in the European Union record that the ClinicalTrials.gov record does not list: meningococcal vaccination

“Has received approved vaccination against Neisseria meningitidis ≥ 6 weeks before administration of RP-A501.” (opens the source at this quote in a new tab)

Exclusion criteria in the European Union record that the ClinicalTrials.gov record does not list

“Prior cardiovascular (CV) surgery, percutaneous coronary intervention (PCI), or valvuloplasty.” (opens the source at this quote in a new tab)
“Greater than moderate valvular stenosis or regurgitation on most recent echocardiographic assessment.” (opens the source at this quote in a new tab)

Eligibility summary presented by the sponsor in October 2026

“Males age ≥8 years, LAMP2 mutation, NYHA II-III, evidence of LV hypertrophy, elevated hsTnI” (opens the source at this quote in a new tab)

Eligibility statements on the recruitment site

“Males, age 8 years or older” (opens the source at this quote in a new tab)
“Have not received a heart transplant” (opens the source at this quote in a new tab)
“this study is not available to those currently participating in any other investigational clinical studies or who have received any other gene therapy treatment” (opens the source at this quote in a new tab)

Exclusion of end-stage heart failure after the phase 1 trial

“These measures include exclusion of patients with end-stage HF” (opens the source at this quote in a new tab)

“The restriction of eligibility to patients with preserved ejection fraction reflects an evolving recognition that advanced myocardial remodeling may be less amenable to reversal.” (opens the source at this quote in a new tab)

Eligibility under the modified protocol: sponsor statement of enhanced criteria (September 2026)

“The modified protocol incorporates a recalibrated RP-A501 dose and an optimized immunomodulatory regimen comprised of rituximab, sirolimus and corticosteroids, together with enhanced eligibility criteria, safety monitoring and risk-mitigation measures.” (opens the source at this quote in a new tab)

Eligibility under the modified protocol: published commentary stating that the criteria were unchanged (September 2026)

“The eligibility criteria remained unchanged.” (opens the source at this quote in a new tab)

Exclusion of genetic predisposition to complement activation, as relayed by an analyst from the May 2025 sponsor call

“one case was linked to a genetic mutation that confers complement sensitivity, and the company has implemented a revised protocol to exclude patients who are genetically predisposed to increased risk for complement activation” (opens the source at this quote in a new tab)

Investigational product and route

“RP-A501 is a gene therapy product consisting of an rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion.” (opens the source at this quote in a new tab)

Dose by cohort in the registry

“Dose of RP-A501: Cohorts 1, 2 & 3 = 6.7 x10^13 genome copies (GC)/kg; Cohort 4 = 3.8 x10^13 GC/kg.” (opens the source at this quote in a new tab)

Immunomodulation regimen by cohort in the registry

“An immunomodulation regimen is initiated before RP-A501 administration to reduce the risk of gene therapy-related complications.” (opens the source at this quote in a new tab)
“The regimen includes rituximab or a biosimilar, administered in two doses for Cohorts 1-3 and three doses for Cohort 4, along with sirolimus and corticosteroids.” (opens the source at this quote in a new tab)
“Pegcetacoplan was incorporated into the immunomodulation regimen for Cohort 3 but excluded in Cohort 4.” (opens the source at this quote in a new tab)

Population, dose, and immunomodulation regimen by cohort in the October 2026 presentation

Cohort	Population	Dose	Immunomodulation regimen
Cohort 1	“Adult/Adolescent (n=1)”	“6.7 x 1013 GC/kg”	“Rituximab + Steroid + Sirolimus”
Cohort 2	“Pediatric (n=3)”	“6.7 x 1013 GC/kg”	“Rituximab + Steroid + Sirolimus”
Cohort 3	“Adult/Adolescent and Pediatric with C3 inhibitor (n=2)”	“6.7 x 1013 GC/kg”	“Rituximab + Steroid + Sirolimus + C3 inhibitor”
Cohort 4	“Adult/Adolescent and Pediatric (n=12)”	“3.8 x 1013 GC/kg”	“Rituximab + Steroid + Sirolimus”

Cohort 4: regimen changes authorized in August 2025

“In addition, Rocket will collaborate with investigators to implement an immunomodulatory regimen more closely reflecting that administered in the Phase 1 pediatric cohort.” (opens the source at this quote in a new tab)
“The revised regimen discontinues prophylactic use of a C3 complement inhibitor, while maintaining sirolimus, rituximab, and steroids.” (opens the source at this quote in a new tab)
“Additionally, the protocol will specify a lower threshold for administering a C5 inhibitor (eculizumab) in response to impending complement activation.” (opens the source at this quote in a new tab)

Cohort 4: treatment received by the first three participants

“The patients received RP-A501 at the recalibrated dose of 3.8 × 10¹³ GC/kg together with a refined immunomodulatory regimen comprised of rituximab, sirolimus, and corticosteroids.” (opens the source at this quote in a new tab)
“Treatment proceeded sequentially, with a minimum of four weeks between infusions.” (opens the source at this quote in a new tab)

Cohort 4: commercial-grade product

“The FDA also confirmed that the pivotal study population will include 12 male patients treated with RP-A501 at the recalibrated dose of 3.8 × 10¹³ genome copies per kilogram (GC/kg) using commercial-grade product.” (opens the source at this quote in a new tab)

Rationale for the 3.8 × 10¹³ GC/kg dose: statement of August 2025

“This adjusted dose aligns with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the Phase 1 study, and has been determined as most likely to confer the safety and efficacy identified in the low-dose Phase 1 cohorts.” (opens the source at this quote in a new tab)

Rationale for the 3.8 × 10¹³ GC/kg dose: full capsid content of the current drug product (August to October 2026)

“The recalibrated Phase 2 dose was selected with the expectation that it will deliver potency consistent with the dose at which RP-A501 demonstrated meaningful efficacy in patients in Phase 1” (opens the source at this quote in a new tab)
“This recalibration accounts for the higher proportion of full capsids in the current drug product in the setting of Danon disease and was developed in consultation with leading experts and the FDA.” (opens the source at this quote in a new tab)

“The recalibrated dose was selected based on analytical characterization of the Phase 2 commercial-grade product, including its full-particle content, and is supported by nonclinical bridging data.” (opens the source at this quote in a new tab)
“In a Danon disease mouse model, administration of Phase 2 material at 3.8 × 10¹³ GC/kg resulted in cardiac LAMP2B protein expression comparable to that observed at a higher dose and demonstrated comparable vector biodistribution.” (opens the source at this quote in a new tab)

“Dose recalibrated to account for the higher full-to-empty capsid ratio” (opens the source at this quote in a new tab)
“Immunomodulation revised based on early Phase 2 safety findings” (opens the source at this quote in a new tab)

History: sponsor statement of February 2025 on the phase 2 drug product relative to phase 1 material

“These batches have superior specifications to Phase 1 material in both titer and full versus empty particles.” (opens the source at this quote in a new tab)
“We believe the improved quality of our in-house manufactured product will allow for full dosing with lower total viral particles, potentially further optimizing the safety profile of RP-A501.” (opens the source at this quote in a new tab)

History: selection of the 6.7 × 10¹³ GC/kg dose for cohorts 1 to 3

“Based on the initial efficacy observed in the low-dose cohort and to mitigate complement-mediated safety concerns observed in the high-dose cohort (related to thrombotic microangiopathy), the Phase 2 study was initiated at the low dose (6.7 × 1013 gc/kg)” (opens the source at this quote in a new tab)

History: administration of the C3 inhibitor in cohort 3

“The C3 inhibitor was given pre- and post-RP-A501 treatment in combination with the enhanced prophylactic immunosuppressive regimen of sirolimus, rituximab (marketed as Rituxan® by Genentech, a member of the Roche Group, and Biogen), and prednisone.” (opens the source at this quote in a new tab)

Duration of immunosuppression

“a refined immunomodulatory regimen involving transient B- and T-cell mediated inhibition, with emphasis on preventing complement activation, while also enabling lower steroid doses and earlier steroid taper, with all immunosuppressive therapy discontinued 2-3 months following administration of RP-A501” (opens the source at this quote in a new tab)

Auxiliary medicinal products listed in the European Union record

“SIROLIMUS, BEKEMV 300 mg concentrate for solution for infusion, SIROLIMUS, PREDNISONE, METHYLPREDNISOLONE SODIUM SUCCINATE, PARACETAMOL, Epysqli 300 mg concentrate for solution for infusion, PREDNISONE, DIPHENHYDRAMINE HYDROCHLORIDE, SIROLIMUS, PREDNISONE, RITUXIMAB, RITUXIMAB, ECULIZUMAB” (opens the source at this quote in a new tab)

Safety monitoring and hospitalization

“Initial patients received RP-A501 at the recalibrated dose of 3.8 × 10¹³ GC/kg with a refined immunomodulatory regimen and enhanced safety monitoring.” (opens the source at this quote in a new tab)
“All 3 patients discharged by 1-2 weeks post-infusion” (opens the source at this quote in a new tab)

“Clinical monitoring team to closely monitor labs, clinical sequelae for AAV-associated toxicities.” (opens the source at this quote in a new tab)

Primary outcome measure in the registry

Field	Registry record
Outcome measure	“Evaluation of Efficacy: Improvement as assessed via primary endpoint comprised of LAMP2 myocardial tissue expression and left ventricular mass index (LVMI)”
Measure description	“Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC), AND, ≥ 10% decrease in LVMI from baseline.”
Time frame	“12 months post-infusion”

Secondary outcome measures in the registry

Outcome measure	Measure description	Time frame
“Evaluation of efficacy via components of the primary endpoint - LAMP2”	“Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC)”	“12 months post infusion”
“Evaluation of efficacy via components of the primary endpoint - Left Ventricular Mass Index (LVMI)”	“≥ 10% decrease in LVMI from baseline”	“12 months post infusion”
“Evaluation of efficacy via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI)”	“≥ 20% decrease in hsTnI from baseline”	“12 months post infusion”
“Evaluation of efficacy via biomarker evidence of myocardial injury - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)”	“≥ 20% decrease in NT-proBNP from baseline”	“12 months post infusion”
“Evaluation of efficacy via Quality of Life”	“Change in KCCQ-12 Overall Score from baseline”	“12 months post infusion”
“Evaluation of efficacy via heart failure symptoms”	“Change in NYHA class from baseline”	“12 months post infusion”
“Evaluation of efficacy via assessment of event-free survival”	“Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization”	“From infusion to 60 months post infusion”
“Evaluation of safety”	“Incidence, severity and duration of treatment emergent safety events.”	“From infusion to 60 months post infusion”

Sponsor description in October 2026: two co-primary endpoints at 12 months, where the registry lists one primary outcome that requires both criteria

“Co-Primary Endpoints (at 12 months): Improvements in LAMP2 protein expression (≥ Grade 1 from baseline) Reductions in Left Ventricular Mass (LVMI; ≥10%)” (opens the source at this quote in a new tab)
“To support accelerated approval, co-primary endpoint consisting of improvements in LAMP2 protein expression (≥ Grade 1 from baseline) and reductions in Left Ventricular Mass (LVMI; ≥10% ↓) at 12-month post-infusion” (opens the source at this quote in a new tab)

Endpoints in the European Union record

“Primary endpoint including myocardial tissue expression of LAMP2 protein and decrease in left ventricular mass index (LVMI). Evaluation of efficacy associated with RP-A501.” (opens the source at this quote in a new tab)
“LAMP2 protein expression, LVMI, hsTnI, NT-proBNP, KCCQ, and NYHA class. Evaluation of efficacy associated with RP-A501.” (opens the source at this quote in a new tab)
“Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization. Evaluation of efficacy associated with RP-A501.” (opens the source at this quote in a new tab)

FDA position reported by the sponsor in December 2022: openness to a biomarker-based composite endpoint

“The FDA has also expressed an openness to considering a biomarker-based composite endpoint supported by functional and quality-of-life assessments as measures of patient benefit.” (opens the source at this quote in a new tab)

FDA alignment reported by the sponsor in September 2023: co-primary endpoint as a basis for accelerated approval

“12 patient study with primary endpoint assessment at 12 months to support accelerated approval” (opens the source at this quote in a new tab)
“To support accelerated approval, the study will assess the efficacy of RP-A501 as measured by the biomarker-based co-primary endpoint consisting of improvements in LAMP2 protein expression (≥ Grade 1, as measured by immunohistochemistry), and reductions in left ventricular (LV) mass.” (opens the source at this quote in a new tab)

“Co-primary endpoint to support accelerated approval consisting of LAMP2 expression & LV Mass reduction of ≥ 10%” (opens the source at this quote in a new tab)
“Study to support AA with a path towards conversion to full approval (with longer follow-up)” (opens the source at this quote in a new tab)

FDA alignment reported by the sponsor in September 2026: the 12-month co-primary endpoints are retained

“FDA confirms established 12-month co-primary endpoints intended to support potential accelerated approval” (opens the source at this quote in a new tab)
“The primary assessment will occur at 12 months using the previously established co-primary endpoints of myocardial LAMP2 protein expression and a 10% reduction from baseline in left ventricular mass index.” (opens the source at this quote in a new tab)
“These endpoints are intended to support a potential accelerated approval pathway.” (opens the source at this quote in a new tab)

Sponsor justification for LAMP2 protein expression (September 2023)

“Primary Endpoint Is Reasonably Likely to Predict Clinical Benefit” (opens the source at this quote in a new tab)
“Mutation of LAMP2 is root cause of Danon disease” (opens the source at this quote in a new tab)
“Epidemiologic support: even modest levels of LAMP2 confer a 2-decade survival advantage in female patients” (opens the source at this quote in a new tab)
“Pre-clinical LAMP2 restoration conferred histologic, functional and survival benefits in LAMP2 knock-out model” (opens the source at this quote in a new tab)
“Phase 1: LAMP2 expression associated with decreased vacuolar area, improved myofibrillar disarray, clinical improvement” (opens the source at this quote in a new tab)
“Absent expression at baseline (Grade 0) in all male patients” (opens the source at this quote in a new tab)
“Efficacy consistent in patients with Grade 1 vs. Grade >1 LAMP2 expression” (opens the source at this quote in a new tab)

Sponsor justification for left ventricular mass (September 2023)

“Severity of the cardiomyopathy in Danon disease is the major prognostic factor” (opens the source at this quote in a new tab)
“Retrospective natural history shows year-over-year increases in LV mass in Danon disease patients” (opens the source at this quote in a new tab)
“Left ventricular hypertrophy is the most consistent phenotypic feature of disease progression” (opens the source at this quote in a new tab)
“Left ventricular wall thickness has been shown to be a significant predictor of CV events in cardiomyopathy” (opens the source at this quote in a new tab)
“In Phase 1 study, LV Mass significantly correlated with improvements / stabilization in all parameters including biomarkers (hsTnI, BNP), quality of life (KCCQ), and symptoms (NYHA)” (opens the source at this quote in a new tab)

Sponsor statement on interpreting the primary endpoint with secondary endpoints and the natural history study

“All components are measurable and unlikely to improve in the absence of a true treatment effect” (opens the source at this quote in a new tab)
“Primary endpoint will be assessed in the context of biomarkers, symptoms, QOL, clinical events derived from secondary endpoints and concurrent natural history study” (opens the source at this quote in a new tab)
“LAMP2 expression and LV Mass are mechanistically linked to functional measures and clinical outcomes; reasonably likely to predict clinical benefit” (opens the source at this quote in a new tab)

LAMP2 immunohistochemistry grading scale (October 2026 presentation)

Grade	Percentage of positive cardiomyocytes as printed
Grade 0	“Grade 0 = no staining”
Grade 1	“Grade 1 (≤25%)”
Grade 2	“Grade 2 (26%–50%)”
Grade 3	“Grade 3 (51%–74%)”
Grade 4	“Grade 4 (≥75%)”

“Grading of LAMP2 protein expression by IHC was done by a board-certified pathologist” (opens the source at this quote in a new tab)
“The semi-quantitative grading reflects the extent of LAMP2 protein expressing cardiomyocytes in the entirety of biopsy sample according to the scale.” (opens the source at this quote in a new tab)

LAMP2 grading scale as printed in the September 2023 presentation, with different boundaries for grades 3 and 4

“Grade 1 ≤25%; Grade 2 =26%-50%; Grade 3 =51%-75%; Grade 4 >75%.” (opens the source at this quote in a new tab)

Phase 1 participants assessed against the phase 2 criteria

“All patients showed ≥10% LVMI decrease and LAMP2 protein expression increase (≥ Grade 1) at ~12m, representing 100% response rate based on pivotal Ph 2 endpoints” (opens the source at this quote in a new tab)

“In the six patients with normal left ventricular ejection fraction at baseline, we observed cardiac LAMP2 protein expression and a reduction from baseline in or stabilization of the left ventricular mass index, preservation of left ventricular ejection fraction, and reduction in or stabilization of the levels of cardiac troponin I and N-terminal pro-B-type natriuretic peptide.” (opens the source at this quote in a new tab)

Durability of LAMP2 staining: one phase 1 participant with Grade 0 staining at 30 and 36 months

“Grade 0 LAMP2 protein IHC staining at the 30- and 36-month assessments, however, LAMP2B vector RNA and DNA (VCN) levels have persisted through 60 months of follow-up” (opens the source at this quote in a new tab)

Left ventricular mass in Danon disease: natural history registry of 116 participants

“LV mass increases in male patients regardless of HF outcome and begins in childhood and continues through adulthood.” (opens the source at this quote in a new tab)
“The results from this study suggest that potential surrogate end points for therapeutic trials could include LVEF, LV mass, LVEDD, and LV wall thickness in male patients, and LVEF, LVEDD, and LV wall thickness in female patients.” (opens the source at this quote in a new tab)

Left ventricular mass in male participants with and without a heart failure outcome (death, transplantation, or ventricular assist device)

Echocardiogram	Heart failure outcome: median (g)	Heart failure outcome: interquartile range	No heart failure outcome: median (g)	No heart failure outcome: interquartile range	P value between groups
First	“327”	“209–541”	“111”	“80–163”	“0.005”
Last	“596”	“285–690”	“161”	“77–377”	“0.020”

Left ventricular mass index and a composite clinical outcome in 22 participants with Danon disease

“A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis.” (opens the source at this quote in a new tab)
“The composite outcome occurred in a total of 7 patients, with 3 of them requiring heart transplantation and 4 requiring implatable cardioverter defibrillator (ICD) for secondary prevention.” (opens the source at this quote in a new tab)
“Univariable analyses for other echocardiographic parameters included LV mass index OR 1.00 (95% CI, 1.00–1.02) with a P value of 0.05” (opens the source at this quote in a new tab)

Hypertrophy and outcomes in hypertrophic cardiomyopathy: wall thickness and sudden death in 480 participants

“The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next.” (opens the source at this quote in a new tab)
“In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis.” (opens the source at this quote in a new tab)

Hypertrophy and outcomes in hypertrophic cardiomyopathy: left ventricular mass index by magnetic resonance in 264 participants

“The LV mass index showed a modest relationship to maximal LV thickness (r(2) = 0.38; p < 0.001)” (opens the source at this quote in a new tab)
“During a 2.6 +/- 0.7-year follow-up, markedly increased LV mass index proved more sensitive in predicting outcome (100%, with 39% specificity), whereas maximal wall thickness >30 mm was more specific (90%, with 41% sensitivity).” (opens the source at this quote in a new tab)

Hypertrophy and outcomes in hypertrophic cardiomyopathy: pooled hazard ratios for maximum wall thickness in a meta-analysis of 19 studies

Outcome	Pooled hazard ratio (95% confidence interval) for maximum left ventricular wall thickness
All-cause death	“1.48 (1.01, 2.17)”
Cardiovascular death	“1.42 (1.06, 1.89)”
Sudden cardiac death	“3.17 (1.64, 6.13)”

“Nineteen studies were included representing 12,146 HCM patients.” (opens the source at this quote in a new tab)

Hazard ratios for hypertrophy measures in other cardiomyopathies as printed in the sponsor's September 2023 presentation

Population as printed	Measure	Event	Hazard ratio as printed
“HFpEF (Shah 2019)”	“LV Mass index”	“CVD or HFH”	“HR 1.05 per 10 g/m(2); CI 1.00 to 1.10; p = 0.03”
“HFpEF (de Simone 2008)”	“LV Mass index”	“HF”	“HR 1.03; CI 1.02-1.04; p<0.00001”
“HCM (Liu 2016)”	“LV wall thickness”	“All Cause Death”	“HR 1.48; CI 1.01 to 2.17; p<0.05”
“HCM (Liu 2016)”	“LV wall thickness”	“CV Death”	“HR 2.17; CI 1.06 to 1.89; p<0.05”
“HCM (Liu 2016)”	“LV wall thickness”	“Sudden Cardiac Death”	“HR 3.17; CI 1.64 to 6.13; p<0.05”
“Fabry Disease (Orsborne 2022)”	“LV Mass index”	“Composite of CV events (HFH, MI, procedures, arrhythmias)”	“HR 1.008; CI 1.003-1.014; p=0.005”
“Fabry Disease (Hanneman 2020)”	“LV Mass index”	“Composite of CV events (HF, ventricular arrhythmia, cardiac death)”	“HR 1.1 per 5 g/m2; CI 1.04-1.2; p<0.001”

Caveat on hypertrophy as a surrogate: stabilization of hypertrophy before heart failure outcomes in male participants

“Left ventricular wall hypertrophy continues in men who have not yet experienced a HF outcome and stabilizes before HF outcome, while females have progressive left ventricular thinning regardless of HF outcome.” (opens the source at this quote in a new tab)
“A major difference in phenotypes between sexes is that in male patients who have not yet experienced HF outcome, LVH continues.” (opens the source at this quote in a new tab)
“These findings suggest that LVEF and LVEDD may be used to predict HF outcome and can be used by clinicians to escalate surveillance intervals and risk stratify patients with DD for advanced therapies.” (opens the source at this quote in a new tab)

Sponsor relationships of the natural history registry publication

“J. Schwartz and S. Turner are employees and shareholders of Rocket Pharmaceuticals.” (opens the source at this quote in a new tab)
“M. Taylor serves as principal investigator on a research grant from Rocket Pharmaceuticals.” (opens the source at this quote in a new tab)

Published commentary on the limits of the available evidence (September 2026)

“The small sample sizes and early-phase design preclude definitive conclusions regarding clinical efficacy or long-term safety.” (opens the source at this quote in a new tab)
“Longer-term follow-up is required to assess durability of gene expression, late toxicity, and clinical outcomes, including survival and survival free from heart transplantation.” (opens the source at this quote in a new tab)

Sponsor disclaimer on the relation between the success criterion and approval

“Meeting the pivotal study’s efficacy success criterion would not, by itself, establish that RP-A501 will receive regulatory approval.” (opens the source at this quote in a new tab)
“FDA’s assessment would consider the complete application, including safety, efficacy, manufacturing and product-quality information.” (opens the source at this quote in a new tab)

Troponin as the key secondary endpoint

“The key secondary endpoint is change in troponin.” (opens the source at this quote in a new tab)

“Early LAMP2, BNP, TnI changes associated with sustained clinical improvement and guided Phase 2 endpoint selection” (opens the source at this quote in a new tab)

Event-free survival: 24 months in sponsor announcements through August 2025 and 60 months in the registry

“Additional secondary endpoints include natriuretic peptides, Kansas City Cardiomyopathy Questionnaire, New York Heart Association class, event free survival to 24 months and treatment emergent safety events.” (opens the source at this quote in a new tab)

“From infusion to 60 months post infusion” (opens the source at this quote in a new tab)

Secondary endpoints as support for conversion to full approval

“These endpoints could support full approval with longer-term follow-up.” (opens the source at this quote in a new tab)

Secondary and exploratory endpoints listed in the September 2023 presentation that the registry does not list

“QoL instruments (KCCQ, PedsQL, PGI-C, PGI-S)” (opens the source at this quote in a new tab)
“6MWT” (opens the source at this quote in a new tab)
“Actigraphy” (opens the source at this quote in a new tab)

Planned enrollment across all four cohorts in the registry

Field	Registry record
Enrollment (estimated)	“18”

Cohort sizes and enrollment status in the registry

Cohort	Registry record
Cohort 1	“N=1 subject; enrollment closed”
Cohort 2	“N= 3 subjects; enrollment closed”
Cohort 3	“N=2 subjects; enrollment closed”
Cohort 4	“N=12 subjects; enrolling”

Pivotal population: 12 participants of cohort 4, of whom 3 had been dosed by September 2026

“The FDA also confirmed that the pivotal study population will include 12 male patients treated with RP-A501 at the recalibrated dose of 3.8 × 10¹³ genome copies per kilogram (GC/kg) using commercial-grade product.” (opens the source at this quote in a new tab)
“Importantly, the first three patients treated at the recalibrated dose under the modified protocol count toward the 12-patient pivotal population, leaving nine additional patients to be enrolled and treated.” (opens the source at this quote in a new tab)

“Current Status: Enrolling and treating remaining Cohort 4 patients (n=9) in Pivotal Phase 2 Study” (opens the source at this quote in a new tab)

Responder definition and success criterion: at least 7 of 12 responders at 12 months

“At least 7 of 12 responders at 12 months” (opens the source at this quote in a new tab)
“Each responder must meet both criteria” (opens the source at this quote in a new tab)
“Myocardial LAMP2 expression ≥ Grade 1 from baseline” (opens the source at this quote in a new tab)
“LVMI reduction ≥10% from baseline” (opens the source at this quote in a new tab)

“Trial success requires at least seven patients to meet both response criteria at 12 months: myocardial LAMP2 protein expression of at least Grade 1 and a reduction in left ventricular mass index of at least 10% from baseline.” (opens the source at this quote in a new tab)

Participants dosed at 6.7 × 10¹³ GC/kg before the clinical hold: 6

“Prior to the clinical hold, six patients with Danon disease were treated with RP-A501 in the Phase 2 study.” (opens the source at this quote in a new tab)

History: 12 participants planned in the September 2023 design

“N=12 patients for pivotal study with potential for primary endpoint readout at 12 months” (opens the source at this quote in a new tab)

History: enrollment of 12 participants reported complete in September 2024

“In September, Rocket announced completion of enrollment in the Phase 2 pivotal study of RP-A501 to treat Danon Disease.” (opens the source at this quote in a new tab)

“In September 2024, we announced completion of enrollment of 12 patients in the Phase 2 study across sites in the U.S. and EU. Dosing and follow-up is ongoing.” (opens the source at this quote in a new tab)

Statistical hypothesis, sample size justification, and method of comparison with the natural history study

No evidence found.

Pivotal efficacy population confirmed by the FDA in September 2026

“FDA confirms pivotal efficacy population of 12 patients, including the first three treated under the modified protocol” (opens the source at this quote in a new tab)

“The FDA-aligned pivotal efficacy population includes 12 male patients receiving commercial-grade RP-A501 at the recalibrated dose.” (opens the source at this quote in a new tab)
“The first three patients treated under the modified protocol count toward this population.” (opens the source at this quote in a new tab)

Cohorts 1 to 3 in relation to the pivotal data package

“Pivotal data package: 12 patients at recalibrated dose + revised immunomodulatory regimen (Cohort 4)” (opens the source at this quote in a new tab)

Preliminary efficacy set: 4 participants of cohorts 1 and 2, with cohort 3 excluded

“Preliminary efficacy in initial 4 patients in Phase 2 further corroborates long-term benefit identified in Phase 1 and LTFU” (opens the source at this quote in a new tab)
“In Phase 2 Cohort 3, two patients treated with immunomodulatory regimen containing a C3-inhibitor experienced serious adverse events. Cohort 3 is discontinued and data from the two subjects were not included.” (opens the source at this quote in a new tab)

Safety reporting groups in the October 2026 presentation

Group	Number of participants as printed
Cohorts 1 and 2	“Cohorts 1 & 2 (n=4)”
Cohort 3	“Cohort 3 (n=2)”
Cohort 4	“Cohort 4 (n=3)”

Protocol definitions of analysis sets and handling of missing biopsy or imaging assessments

No evidence found.

Participants by cohort in the October 2026 presentation: 6 dosed in cohorts 1 to 3 and 12 planned in cohort 4

Cohort	Participants as printed
Cohort 1	“Adult/Adolescent (n=1)”
Cohort 2	“Pediatric (n=3)”
Cohort 3	“Adult/Adolescent and Pediatric with C3 inhibitor (n=2)”
Cohort 4	“Adult/Adolescent and Pediatric (n=12)”

Cohort 2 included the pediatric safety run-in

“Included initial sequential Pediatric Safety Run-in (n=2)” (opens the source at this quote in a new tab)

Six participants treated at 6.7 × 10¹³ GC/kg before dosing was paused in May 2025

“To date, six patients with Danon disease have been treated in the Phase 2 study with RP-A501.” (opens the source at this quote in a new tab)

“Upon learning of the initial event, Rocket voluntarily paused further dosing in the study.” (opens the source at this quote in a new tab)

One death among the 6 participants treated before the clinical hold

“One subject developed bacteremia and sepsis which subsequently resulted in death on 25-May-2025.” (opens the source at this quote in a new tab)

Follow-up of the 4 participants of cohorts 1 and 2 at the data extraction of August 7, 2026

Participant	Cohort as printed	Most recent visit (months)
2-1	“Cohort 1: Adult/ Adolescent”	“24”
2-2	“Cohort 2: Pediatric”	“36”
2-3	“Cohort 2: Pediatric”	“24”
2-4	“Cohort 2: Pediatric”	“18”

Cohort 4: 3 of 12 participants dosed, with 9 remaining as of October 6, 2026

“Current Status: Enrolling and treating remaining Cohort 4 patients (n=9) in Pivotal Phase 2 Study” (opens the source at this quote in a new tab)
“All 3 patients discharged by 1-2 weeks post-infusion” (opens the source at this quote in a new tab)

“All three completed at least four weeks of follow-up and had been discharged following protocol-specified observation.” (opens the source at this quote in a new tab)

“All three patients have completed the protocol-defined safety observation period” (opens the source at this quote in a new tab)

Status of participants enrolled by September 2024 who were not dosed before the clinical hold

No evidence found.

Cohorts 1 and 2: age at the most recent visit (data extraction August 7, 2026)

Participant	Cohort as printed	Age at most recent visit (years)	Most recent visit (months)
2-1	“Cohort 1: Adult/ Adolescent”	“20”	“24”
2-2	“Cohort 2: Pediatric”	“16”	“36”
2-3	“Cohort 2: Pediatric”	“15”	“24”
2-4	“Cohort 2: Pediatric”	“12”	“18”

Cohorts 1 and 2: baseline value and most recent value of disease measures, printed as baseline to most recent visit

Participant	Left ventricular mass index (g/m2.7)	NT-proBNP (ng/L)	Cardiac troponin I (ng/mL)	NYHA class	KCCQ-12 overall score
2-1	“65.5 to 41.9”	“125 to 101”	“0.04 to 0.02”	“II to I”	“100 to 100”
2-2	“65.4 to 42.8”	“54 to 50”	“0.02 to 0.01”	“II to I”	“98 to 100”
2-3	“187.1 to 204.8”	“7966 to 6465”	“0.33 to 0.73”	“III to I”	“64 to 79”
2-4	“202.2 to 140.5”	“69855 to 49135”	“0.82 to 0.71”	“II to II”	“35 to 71”

Baseline characteristics of the participants of cohorts 3 and 4

No evidence found.

Race, ethnicity, LAMP2 variant type, and implanted device status of phase 2 participants

No evidence found.

Primary endpoint results in the pivotal cohort: readout targeted for mid-2028

“Primary efficacy readout from pivotal Cohort 4” (opens the source at this quote in a new tab)
“MID-2028 target is provisional pending alignment with dosing completion and 12-month follow-up.” (opens the source at this quote in a new tab)

Cohorts 1 and 2 (6.7 × 10¹³ GC/kg): change in left ventricular mass index and wall thickness from baseline to the most recent visit (data extraction August 7, 2026)

Participant	Most recent visit (months)	Left ventricular mass index (g/m2.7)	Interventricular septum in diastole (mm)	Left ventricular posterior wall in diastole (mm)
2-1	“24”	“-36%, 65.5 to 41.9”	“-28%, 21.8 to 15.6”	“-7%, 16.5 to 15.4”
2-2	“36”	“-35%, 65.4 to 42.8”	“-39%, 16.0 to 9.7”	“-10%, 10.4 to 9.4”
2-3	“24”	“+9%, 187.1 to 204.8”	“-4%, 28.2 to 27.1”	“-17%, 26.1 to 21.7”
2-4	“18”	“-30%, 202.2 to 140.5”	“+17%, 39.3 to 46.0”	“+24%, 22.5 to 27.9”

Cohorts 1 and 2 (6.7 × 10¹³ GC/kg): change in NT-proBNP and cardiac troponin I from baseline to the most recent visit (data extraction August 7, 2026)

Participant	Most recent visit (months)	NT-proBNP (ng/L)	Cardiac troponin I (ng/mL)
2-1	“24”	“-19%, 125 to 101”	“-49%, 0.04 to 0.02”
2-2	“36”	“-7%, 54 to 50”	“-14%, 0.02 to 0.01”
2-3	“24”	“-19%, 7966 to 6465”	“+122%, 0.33 to 0.73”
2-4	“18”	“-30%, 69855 to 49135”	“-14%, 0.82 to 0.71”

Cohorts 1 and 2: 3 of 4 participants with a reduction in left ventricular mass index of at least 10%

“Three of four patients with longitudinal efficacy assessments achieved at least a 10% reduction in left ventricular mass index.” (opens the source at this quote in a new tab)

Sponsor description of the preliminary findings

“Preliminary findings show stabilization or improvement in key disease measures” (opens the source at this quote in a new tab)
“Improvement or stabilization of cardiac hypertrophy, heart failure symptoms, quality of life scores, and biomarkers of cardiac injury and stress replicate the trajectory of Phase 1 responders” (opens the source at this quote in a new tab)

Measurement method for the preliminary echocardiographic results

“All measurements of cardiac structure and function (LVEF, LV Mass, LVMI, IVSd and LVPWd) utilized centrally evaluated echocardiogram data (blinded review) for all participants.” (opens the source at this quote in a new tab)

Cohort 3: efficacy data excluded

“Cohort 3 is discontinued and data from the two subjects were not included.” (opens the source at this quote in a new tab)

Sponsor cautions on the preliminary data

“Clinical observations presented here are based on small, uncontrolled studies with varying follow-up.” (opens the source at this quote in a new tab)
“Preliminary findings may change as additional data become available, and results from earlier cohorts may not predict outcomes at the recalibrated dose under the modified protocol.” (opens the source at this quote in a new tab)

Myocardial LAMP2 protein expression in phase 2 participants

No evidence found.

Twelve-month values and responder status on the co-primary criteria in cohorts 1 and 2

No evidence found.

Efficacy results in cohort 4

No evidence found.

Event-free survival and comparison with the natural history study

No evidence found.

Cohorts 1 and 2: KCCQ-12 overall score and NYHA class from baseline to the most recent visit (data extraction August 7, 2026)

Participant	Most recent visit (months)	KCCQ-12 overall score: change, baseline to most recent visit	NYHA class
2-1	“24”	“0, 100 to 100”	“II to I”
2-2	“36”	“+2, 98 to 100”	“II to I”
2-3	“24”	“+16, 64 to 79”	“III to I”
2-4	“18”	“+35, 35 to 71”	“II to II”

Registered quality of life and symptom outcome measures

“Change in KCCQ-12 Overall Score from baseline” (opens the source at this quote in a new tab)
“Change in NYHA class from baseline” (opens the source at this quote in a new tab)

Results for PedsQL, PGI-C, PGI-S, 6-minute walk test, and actigraphy

No evidence found.

Quality of life and symptom results in cohorts 3 and 4

No evidence found.

Grade 3 or higher serious treatment-emergent adverse events related to RP-A501, by cohort: number of participants (%) (data extraction August 7, 2026)

Preferred term	Cohorts 1 and 2 (n=4)	Cohort 3 (n=2)	Cohort 4 (n=3)
Participants with at least 1 event	“3 (75.0)”	“2 (100)”	“1 (33.3)”
Thrombotic microangiopathy	“2 (50.0)”	“1 (50.0)”	“0”
Acute kidney injury	“1 (25.0)”	“1 (50.0)”	“0”
Renal failure	“1 (25.0)”	“0”	“0”
Gamma-glutamyltransferase increased	“0”	“0”	“1 (33.3)”
Hepatic enzyme increased	“1 (25.0)”	“0”	“0”
Cardiac arrest	“1 (25.0)”	“0”	“0”
Posterior reversible encephalopathy syndrome	“1 (25.0)”	“0”	“0”
Rhabdomyolysis	“1 (25.0)”	“0”	“0”
Aplastic anemia	“0”	“1 (50.0)”	“0”
Disseminated intravascular coagulation	“0”	“1 (50.0)”	“0”
Cytokine release syndrome	“0”	“1 (50.0)”	“0”
Hypertransaminasaemia	“0”	“1 (50.0)”	“0”
Pneumothorax	“0”	“1 (50.0)”	“0”
Sepsis	“0”	“1 (50.0)”	“0”
Shock	“0”	“1 (50.0)”	“0”
Retroperitoneal hemorrhage	“0”	“1 (50.0)”	“0”

Participants with the tabulated thrombotic microangiopathy and gamma-glutamyltransferase events

“Grade ≥3 Serious Treatment Emergent Adverse Events Related to RP-A501” (opens the source at this quote in a new tab)
“Patients 2-3, 2-4 and 2-6” (opens the source at this quote in a new tab)
“Patient 2-8” (opens the source at this quote in a new tab)

Cohorts 1 and 2: thrombotic microangiopathy before the C3 inhibitor was added, as relayed by an analyst from the May 2025 sponsor call

“the patient who died had received a marketed C3 complement inhibitor as a part of an amended immunosuppression protocol that was enacted following at least two cases of thrombotic microangiopathy (TMA) during the trial” (opens the source at this quote in a new tab)
“the patients that did develop TMA earlier in the trial are doing well now from a safety perspective” (opens the source at this quote in a new tab)

Cohort 3: capillary leak syndrome in 2 participants in May 2025

“In May 2025, two patients participating in the Phase 2 pivotal study of RP-A501 each experienced an unexpected SAE.” (opens the source at this quote in a new tab)
“The SAEs involved clinical complications related to a capillary leak syndrome resulting in multi-organ damage; one patient died as a result of these complications following an acute systemic infection.” (opens the source at this quote in a new tab)

“The SAEs involved clinical complications related to a capillary leak syndrome and were followed by a systemic infection and multi-organ damage, ultimately leading to one of the patient’s deaths.” (opens the source at this quote in a new tab)

Cohort 3: initial public report of the first event (May 27, 2025)

“A patient participating in the Phase 2 pivotal trial of RP-A501 experienced an unexpected Serious Adverse Event (SAE).” (opens the source at this quote in a new tab)
“The SAE involved clinical complications related to a capillary leak syndrome.” (opens the source at this quote in a new tab)
“Rocket is deeply saddened to report that this patient has since passed away after an acute systemic infection.” (opens the source at this quote in a new tab)

Cohort 3: course of the two events as reported from the May 2025 sponsor call

“During the conference call, Shah said the patient experienced signs of CLS about a week after receiving RP-A501 in early May.” (opens the source at this quote in a new tab)
“A second patient also received the modified immunosuppression regimen, including the C3 inhibitor, and also exhibited early signs of CLS but had a reduced course of the C3 inhibitor” (opens the source at this quote in a new tab)

“Two patients received the immune suppression agent, company CEO Gaurav Shah explained on a conference call Tuesday morning.” (opens the source at this quote in a new tab)
“Rocket was able to reduce the treatment course the second patient received after seeing early signs of capillary leak syndrome in the first.” (opens the source at this quote in a new tab)

Cohort 3: death on May 25, 2025, as notified in the European Union record

“This was based on previously reported SAEs events (CIOMS submission dates of 15-May-2025 and 20-May-2025).” (opens the source at this quote in a new tab)
“Subsequently, the Sponsor received FDA notification of clinical hold.” (opens the source at this quote in a new tab)
“One subject developed bacteremia and sepsis which subsequently resulted in death on 25-May-2025.” (opens the source at this quote in a new tab)

Capillary leak in participants with Danon disease given complement inhibitor prophylaxis, as described at a scientific meeting in March 2026 (the article does not name the trial)

“Another series of patients with LAMP2-deficiency (Danon disease) who experienced a similar toxicity after receiving IV AAV9 gene therapy was recently described by Jonathan Schwartz at a joint American Society of Cell & Gene Therapy (ASGCT)/Association of Regenerative Medicine (ARM) conference on 7 March 2026.” (opens the source at this quote in a new tab)
“In that study, patients had received prophylactic treatment with pegacetoplan, an FDA-approved complement inhibitor, and investigators suspect that pegacetoplan facilitated binding of a low concentration complement complexes to endothelial cells to cause diffuse capillary leak, which manifested as pulmonary edema and hemoconcentration.” (opens the source at this quote in a new tab)

Sponsor's initial hypothesis on the cause (May 27, 2025)

“Rocket is conducting a comprehensive root cause analysis and remains in active dialogue with the U.S. Food and Drug Administration (FDA) and other key stakeholders, with the current focus being on the recent introduction of a novel immune suppression agent to the pre-treatment regimen that had been implemented to mitigate complement activation observed in some patients.” (opens the source at this quote in a new tab)
“This novel agent was specific to the AAV9-Danon program.” (opens the source at this quote in a new tab)

Cause of the capillary leak events as reported by the sponsor after the FDA review

“In August 2025, the FDA lifted the clinical hold on the Phase 2 pivotal study following an investigation which concluded that the SAEs were likely the result of the combination of the C3 complement inhibitor introduced into the immunomodulation regimen and RP-A501.” (opens the source at this quote in a new tab)

“after the investigation traced the unexpected SAEs to a protocol amendment that added a C3 inhibitor to the immunomodulatory regimen” (opens the source at this quote in a new tab)

“In its correspondence, the FDA confirmed that Rocket satisfactorily addressed issues outlined in the clinical hold.” (opens the source at this quote in a new tab)

Proposed mechanism in published commentary

“A potential mechanism has subsequently been proposed, whereby complement inhibition with the C3 inhibitor may have reduced AAV opsonization and increased vector uptake by endothelial cells, leading to vascular endothelial injury” (opens the source at this quote in a new tab)

Cohort 4 (3.8 × 10¹³ GC/kg): safety update of August 3, 2026

“To date, no thrombotic microangiopathy (TMA), capillary leak syndrome, or other significant safety concerns have been observed in these patients.” (opens the source at this quote in a new tab)

Cohort 4: data reviewed by the FDA (September 2026)

“The clinical data reviewed by FDA included results from the first three patients treated under the modified protocol.” (opens the source at this quote in a new tab)
“No clinical or laboratory evidence of thrombotic microangiopathy or capillary leak syndrome had been observed.” (opens the source at this quote in a new tab)

Cohort 4: safety through 3 months in the first three participants (safety data as of September 4, 2026)

“No TMA, capillary leak, or significant complement-mediated adverse events through 3 months in the first three patients” (opens the source at this quote in a new tab)
“Elevated GGT observed in 1 patient; resolved and patient discharged after 12 days.” (opens the source at this quote in a new tab)
“One RP-A501-related Grade 3 increase in gamma-glutamyltransferase (GGT) was reported and resolved.” (opens the source at this quote in a new tab)
“Initial safety follow-up is limited for Phase 2 Cohort 4.” (opens the source at this quote in a new tab)
“Safety data as of September 4, 2026.” (opens the source at this quote in a new tab)

Cohort 4: platelet count and terminal complement complex (sC5b9) monitoring (data extraction September 4, 2026)

“Platelets and Terminal Complement Complex (sC5b9) of the initial 3 patients up to 3 months post-treatment” (opens the source at this quote in a new tab)
“A decrease in platelet count was observed at Week 8-9 in the absence of symptoms or signs suggestive of platelet dysfunction or deficit.” (opens the source at this quote in a new tab)
“All concomitant medications were reviewed to discontinue any potential contributors; it was not deemed clinically significant by the investigator and Sponsor and resolved following medication modifications.” (opens the source at this quote in a new tab)
“The sC5b9 lower limit of detection per the validated assay at the clinical site is <170 ng/mL; reported values of <170 ng/mL are shown as 170 ng/mL.” (opens the source at this quote in a new tab)

Sponsor description of the safety findings at 6.7 × 10¹³ GC/kg in October 2026

“Safety findings from the original-dose study, including thrombotic microangiopathy and a fatal serious adverse reaction, informed the recalibrated dose, revised immunomodulation regimen and enhanced safety monitoring now in place.” (opens the source at this quote in a new tab)

Allegation in securities litigation concerning disclosure of serious adverse events in the trial

“Among other things, Plaintiffs allege that Defendants failed to disclose certain SAEs that impacted patients during the Phase 2 clinical trial and the introduction of a C3 inhibitor to the trial’s protocol and that Defendants purportedly lacked a viable trial design that could safely and effectively dose patients while managing the risk of serious adverse events.” (opens the source at this quote in a new tab)
“We intend to vigorously defend against the consolidated amended complaint’s allegations.” (opens the source at this quote in a new tab)

Incidence of all adverse events, non-serious events, and events below Grade 3

No evidence found.

Summary

RP-A501-0123 is a single-arm, open-label trial without randomization or a concurrent control arm. The comparison group is an external natural history study, and no document found states the statistical hypothesis, the sample size justification, or the method of comparison with that study. The registry lists one primary outcome at 12 months that requires both myocardial LAMP2 protein expression of Grade 1 or higher by immunohistochemistry and a decrease of 10% or more in left ventricular mass index; the sponsor describes these as co-primary endpoints intended to support accelerated approval, with success defined as at least 7 of 12 responders. Both criteria are surrogate measures, and event-free survival is a secondary outcome followed to 60 months. In a natural history registry of 116 participants, left ventricular hypertrophy in male participants stabilized before heart failure outcomes, and the authors named ejection fraction and end-diastolic dimension as the measures that may predict those outcomes. Enrollment is restricted to males aged 8 years and older with a left ventricular ejection fraction of 50% or more and NYHA class II to III symptoms, so the trial provides no evidence for females, for children younger than 8 years, or for participants with reduced ejection fraction.

The design changed after the safety events of May 2025. The original plan was 12 participants at 6.7 × 10¹³ GC/kg, and 6 participants were dosed at that dose in three cohorts. The 2 participants of cohort 3 received an immunomodulation regimen containing pegcetacoplan and both developed capillary leak syndrome; 1 of them died after an acute systemic infection. The pivotal population is now the 12 participants of cohort 4, who receive 3.8 × 10¹³ GC/kg with three doses of rituximab and no pegcetacoplan, and 3 of the 12 had been dosed as of October 2026. All available efficacy data come from the 4 participants of cohorts 1 and 2, who received a dose and an immunomodulation regimen different from those of the pivotal cohort; the sponsor states that “results from earlier cohorts may not predict outcomes at the recalibrated dose under the modified protocol”. Those data are baseline to most recent visit values at 18 to 36 months, no myocardial LAMP2 protein expression result for a phase 2 participant has been presented, and data from the 2 participants of cohort 3 were excluded. Among those 4 participants, 3 (75.0%) had a Grade 3 or higher serious adverse event related to RP-A501, including thrombotic microangiopathy in 2 (50.0%). Safety follow-up of cohort 4 is limited to about 3 months in 3 participants. No peer-reviewed report of phase 2 results was found, and the registry record has no results posted. Every phase 2 result cited here is reported by the sponsor in press releases, an investor presentation, and securities filings, and platelet and complement values for cohort 4 are shown only as charts. The status of participants counted in the September 2024 enrollment of 12 who were not dosed before the clinical hold is not stated.

Registered study purpose

“This is a non-randomized open-label Phase 1 study to evaluate the safety and toxicity of gene therapy using a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).” (opens the source at this quote in a new tab)
“The study will also enable an initial evaluation of whether or not the IP results in cardiomyocyte and skeletal muscle transduction and gene expression and preliminary assessment of the extent of cardiomyocyte and histologic correction.” (opens the source at this quote in a new tab)
“Additionally, a preliminary evaluation of clinical stabilization following infusion will also be made.” (opens the source at this quote in a new tab)

Objective stated in the publication abstract

“In this phase 1 study, we evaluated the safety and efficacy of a single infusion of RP-A501, a recombinant adeno-associated virus serotype 9 containing the transgene LAMP2B, which encodes an isoform of LAMP2.” (opens the source at this quote in a new tab)

Objective stated by the sponsor at clearance of the investigational new drug application, January 2019

“We expect to initiate a Phase 1, first-in-human study in the U.S. in the second quarter of 2019 to assess the safety, tolerability and preliminary efficacy of RP-A501.” (opens the source at this quote in a new tab)

Objective of the pediatric cohort stated in a congress abstract

“In this initial pediatric cohort, there was specific emphasis on minimization of immune responses, particularly complement activation and thrombotic microangiopathy (TMA) that have been associated with systemic AAV therapy in pediatric and adult evaluations in monogenic neuromuscular, metabolic and coagulation disorders.” (opens the source at this quote in a new tab)

Study dates and status in the registry

Milestone	Registry record
Study start (actual)	“2019-04-17”
Primary completion (actual)	“2025-07-03”
Study completion (actual)	“2025-07-03”
First posted	“2019-03-20”
Last update posted	“2026-10-06”
Recruitment status	“Completed”

Registered locations

“This study has 3 locations” (opens the source at this quote in a new tab)

Site	City as registered
“University of California, San Diego”	“La Jolla, California, United States, 92037”
“University of Colorado”	“Aurora, Colorado, United States, 80045”
“Children's Hospital of Philadelphia”	“Philadelphia, Pennsylvania, United States, 19104”

Sites at which the seven participants were treated

Age group	Participants and site
Adults and adolescents (>15 years)	“n=5, at UCSD”
Pediatric (8-14 years)	“n=2, both at CHOP”

Clearance of the investigational new drug application, January 2019

“today announces the clearance of the Company’s Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for RP-A501” (opens the source at this quote in a new tab)
“UC San Diego Health will be the initial and lead center for the planned Phase 1 clinical trial under the direction of Eric Adler, M.D., Director of Cardiac Transplant and Mechanical Circulatory Support at UC San Diego Health and Professor of Medicine at University of California San Diego School of Medicine.” (opens the source at this quote in a new tab)

Period over which the seven participants were dosed

“Between June 2019 and March 2022, 7 males with DD age 11.7 - 21.1y (median 18.3y; N=5 adult and N=2 pediatric) received RP-A501 (N=5 low dose and N=2 high dose).” (opens the source at this quote in a new tab)

FDA request to pause dosing, announced May 10, 2021

“The U.S. Food and Drug Administration (FDA) has requested the Company to pause patient dosing and modify the protocol and other supporting documents with revised guidelines for patient selection and management.” (opens the source at this quote in a new tab)
“No new drug-related safety events have been observed in the low- or high-dose adult cohorts of the Phase 1 trial.” (opens the source at this quote in a new tab)
“All follow-up study activities will continue and no additional data are requested.” (opens the source at this quote in a new tab)
“We have successfully treated five patients in the low- and high-dose adult cohorts.” (opens the source at this quote in a new tab)

Clinical hold from May 2021 to August 16, 2021

“On May 10, 2021, we announced that the RP-A501 Danon Disease program was placed on clinical hold by the FDA.” (opens the source at this quote in a new tab)
“On August 16, 2021, the FDA lifted the clinical hold on our Danon Disease program allowing patient enrollment in our Phase 1 clinical trial of RP-A501 for the treatment of Danon Disease to resume.” (opens the source at this quote in a new tab)
“The hold was removed after we addressed the FDA’s requests to modify the trial protocol and other supporting documents with revised guidelines for patient selection and management.” (opens the source at this quote in a new tab)
“The FDA lifted the clinical hold on August 16, 2021 and dosing of the pediatric cohort was initiated in September 2021.” (opens the source at this quote in a new tab)

Status in October 2026: three-year study completed and long-term follow-up ongoing

“Phase 1: 3 years (completed)” (opens the source at this quote in a new tab)
“Phase 1 LTFU: up to 10 years (ongoing)” (opens the source at this quote in a new tab)

Registry design fields

Field	Registry record
Study type	“Interventional”
Phase	“Phase 1”
Primary purpose	“Treatment”
Allocation	“N/A”
Interventional model	“Sequential Assignment”
Masking	“None (Open Label)”

Non-randomized, open-label trial of a single intravenous infusion

“The study is a non-randomized open-label Phase I clinical trial to characterize the safety and toxicity associated with infusion of a recombinant adeno-associated serotype 9 (rAAV9) capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).” (opens the source at this quote in a new tab)
“During the course of the study, approximately 7-10 male subjects age 8 and over will receive a single intravenous (IV) infusion of the IP.” (opens the source at this quote in a new tab)

Sequential cohorts by age and dose in the registry

“Evaluation of RP-A501 in pediatric patients (ages 8-14) will commence only pending determination of safety in the older (adult and age 15-17) population.” (opens the source at this quote in a new tab)
“In Phase 1, RP-A501 will be investigated in three treatment cohorts, as follows with a single cohort currently recruiting:” (opens the source at this quote in a new tab)
“Cohort 1: Adult and age 15-17: 6.7 × 1013 GC/kg (n=3-4)” (opens the source at this quote in a new tab)
“Cohort 2: Adult and age 15-17: 1.1 × 1014 GC/kg (n=2 [patients already treated; closed for current enrollment])” (opens the source at this quote in a new tab)
“Cohort 1A: Pediatric age 8-14: 6.7 × 1013 GC/kg (n=2-4)” (opens the source at this quote in a new tab)

Escalating dose cohorts described by the sponsor in December 2020

“The non-randomized, open-label Phase 1 trial was designed to enroll both pediatric and young adult male patients in escalating dose cohorts.” (opens the source at this quote in a new tab)

“IND enables doses up to 2.0 x 1014 GC/kg” (opens the source at this quote in a new tab)

Design described by the sponsor as single-arm, open-label, and multicenter

“We treated seven patients in the single-arm, open-label, multi-center Phase 1 clinical trial assessing the safety and preliminary efficacy of RP-A501, which enrolled adult/older adolescent and pediatric male DD patients.” (opens the source at this quote in a new tab)

Follow-up of 36 months, then a long-term follow-up study of 2 to 5 further years in the registry

“All patients are planned to be followed for 36 months after investigational product administration.” (opens the source at this quote in a new tab)
“After the end of the follow-up period, patients will enter a Long-Term Follow-Up (LTFU) study enabling follow-up for an additional 2 to 5 years post-IP administration.” (opens the source at this quote in a new tab)

Long-term follow-up of up to 10 years stated in October 2026

“Phase 1 LTFU: up to 10 years (ongoing)” (opens the source at this quote in a new tab)

Interim long-term follow-up data included in the publication

“Phase 1 data over 24 to 54 months, including interim data from a long-term follow-up study, are reported here.” (opens the source at this quote in a new tab)

Protocol change: exclusion of ejection fraction below 40% before the pediatric cohort

“LVEF <40% (implemented prior to enrolling pediatric cohort)” (opens the source at this quote in a new tab)

“Of note, this patient had advanced features of heart failure upon treatment; the updated trial protocol will exclude enrollment of Danon patients with end-stage disease.” (opens the source at this quote in a new tab)

Protocol change: discontinuation of the higher dose in agreement with the FDA

“Given the activity observed in the low dose cohort and to mitigate TMA and associated safety concerns observed in the high dose cohort, in agreement with FDA we will focus on the low dose moving forward (6.7e13) and will no longer administer the higher doses (1.1e14 or higher) in this trial.” (opens the source at this quote in a new tab)
“Additional safety measures have been implemented and are reflected in the updated trial protocol.” (opens the source at this quote in a new tab)

Safety measures in the updated protocol

“Additional safety measures were implemented and are reflected in the updated trial protocol for Phase 1 and the protocol for our ongoing pivotal Phase 2 study.” (opens the source at this quote in a new tab)
“These measures include exclusion of patients with end-stage HF, and a refined immunomodulatory regimen involving transient B- and T-cell mediated inhibition, with emphasis on preventing complement activation, while also enabling lower steroid doses and earlier steroid taper, with all immunosuppressive therapy discontinued 2-3 months following administration of RP-A501.” (opens the source at this quote in a new tab)

Monitoring measures implemented before pediatric enrollment

“Enhanced monitoring for early signs of TMA for potential early use of Eculizumab” (opens the source at this quote in a new tab)
“Clinical Monitoring Team included 2 independent monitors with expertise in TMA” (opens the source at this quote in a new tab)
“No further enrollment at higher dose level” (opens the source at this quote in a new tab)

Separate registry record for the long-term follow-up study

No evidence found.

Registry eligibility fields

Field	Registry record
Ages eligible for study	“8 Years and older (Child, Adult, Older Adult )”
Sexes eligible for study	“Male”
Accepts healthy volunteers	“No”

Inclusion: population and consent

“The study will enroll adult and pediatric males with a confirmed diagnosis of DD. Patients may be of any race or ethnicity.” (opens the source at this quote in a new tab)
“Patients and/or competent custodial parents must provide informed written consent and meet all of the enrollment criteria as detailed subsequently to be eligible to participate.” (opens the source at this quote in a new tab)
“Ability to provide informed consent (for adult patients and parents/legal guardians of pediatric patients) and assent (for patients age 15-17).” (opens the source at this quote in a new tab)
“Ability to comply with study procedures including investigational therapy and follow-up evaluations.” (opens the source at this quote in a new tab)

Inclusion: diagnosis, cardiac involvement, age, sex, and functional class

“DD diagnosis with any confirmed LAMP2 mutation(s).” (opens the source at this quote in a new tab)
“Cardiac involvement as documented by at least one abnormal finding on electrocardiogram (ECG), echocardiogram, gadolinium-enhanced cardiac magnetic resonance imaging (MRI), or electrophysiology study.” (opens the source at this quote in a new tab)
“Age ≥15 years for cohorts 1 and 2; 8-14 years for cohorts 1A.” (opens the source at this quote in a new tab)
“Male gender.” (opens the source at this quote in a new tab)
“New York Heart Association (NYHA) Class II or III.” (opens the source at this quote in a new tab)
“Able to walk >150 meters unassisted during the 6MWT.” (opens the source at this quote in a new tab)

Inclusion: hematologic, hepatic, and renal function

“Adequate hematologic function as defined by hemoglobin, absolute neutrophil count (ANC), and platelet count ≥ lower limit of normal (LLN).” (opens the source at this quote in a new tab)
“AST and ALT ≤10.0×ULN or GGT ≤2.0×ULN (transaminase elevations in DD are considered extensively to result from muscle injury; hence the relatively high upper limit for transaminases and consideration of GGT level, and the presence of additional hepatic eligibility markers of bilirubin and PT/INR).” (opens the source at this quote in a new tab)
“Serum bilirubin ≤1.2×ULN (i.e., Grade ≤1 bilirubin increase).” (opens the source at this quote in a new tab)
“PT/INR ≤1.2×ULN (in the absence of anticoagulation).” (opens the source at this quote in a new tab)
“Absence of cirrhosis or other signs of inflammation on liver ultrasound” (opens the source at this quote in a new tab)
“Adequate renal function as defined by creatinine ≤ULN.” (opens the source at this quote in a new tab)

Inclusion: meningococcal vaccination

“Patient has received meningococcal vaccination recommended by Centers for Disease Control as appropriate for age and health condition (vaccination must be performed at least 6 weeks prior to IP administration).” (opens the source at this quote in a new tab)

Exclusion: cardiac status and prior cardiac procedures

“I.V. therapy with positive inotropes, vasodilators, or diuretics within the 30 days prior to enrollment (i.e., patient must be stable on oral medical therapy).” (opens the source at this quote in a new tab)
“Prior cardiac transplantation or prior transplant of other organ (lung, liver, other).” (opens the source at this quote in a new tab)
“Prior cardiac surgery and/or percutaneous cardiac intervention for arteriothrombotic complications, or valvuloplasty.” (opens the source at this quote in a new tab)
“Presence or requirement of a Left Ventricular Assisted Device (LVAD).” (opens the source at this quote in a new tab)
“Left ventricular ejection fraction (LVEF) <40% at baseline.” (opens the source at this quote in a new tab)
“Significant (greater than moderate) valvular stenosis or regurgitation on echocardiogram.” (opens the source at this quote in a new tab)
“Requires mechanical ventilation.” (opens the source at this quote in a new tab)

Exclusion: thrombotic and thromboembolic history

“History of intracardiac thrombosis or arteriothromboembolic events including stroke or transient ischemic attack (TIA).” (opens the source at this quote in a new tab)
“History of the following prior arteriothromboembolic complications: myocardial infarction or unstable angina.” (opens the source at this quote in a new tab)

Exclusion: anti-AAV9 neutralizing antibodies and concurrent investigational agents

“Anti-AAV9 neutralizing antibody titer >1:40.” (opens the source at this quote in a new tab)
“Concurrent enrollment in any other clinical investigation involving use of an investigational agent for the treatment of CHF or cardiomyopathy.” (opens the source at this quote in a new tab)

Exclusion: infection

“Active hepatitis B or C infection (including patients with positive hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), or detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load). Patients with previous, adequately resolved HBV or HCV are eligible.” (opens the source at this quote in a new tab)
“Significant medical conditions including documented human immunodeficiency virus (HIV) infection, active viral or other hepatitis, poorly-controlled hypertension or diabetes, poorly controlled cardiac arrhythmia, or uncontrolled viral, bacterial, or fungal infection.” (opens the source at this quote in a new tab)
“Active or latent tuberculosis.” (opens the source at this quote in a new tab)

Exclusion: malignancy, sirolimus contraindication, and investigator judgment

“Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or other carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years.” (opens the source at this quote in a new tab)
“Any contraindication to use of sirolimus which includes hypersensitivity to sirolimus or HC-60 (polyoxyl 60 hydrogenated castor oil).” (opens the source at this quote in a new tab)
“Any concomitant medical or psychiatric condition that in the opinion of the Investigator renders the patient unfit for study participation or at higher than acceptable risk for study participation.” (opens the source at this quote in a new tab)

Entry criteria shown by the sponsor in December 2020, before the protocol changes

“NYH Class II/III or Class I with decreased 6MWT” (opens the source at this quote in a new tab)
“AST/ALT < 10 X ULN; GGT < 2 X ULN; BR < 1.5 X ULN; no liver cirrhosis by U.S.” (opens the source at this quote in a new tab)

Investigational product and route of administration

“RP-A501 is a gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single intravenous (IV) infusion.” (opens the source at this quote in a new tab)
“Subjects will receive one of three dose levels depending on the cohort.” (opens the source at this quote in a new tab)

Dose and number of participants by cohort

“This includes a first cohort evaluating a low-dose (6.7e13 genome copies/kilogram ([gc/kg]; n=3) in adult/older adolescent patients aged 15 or greater, a second cohort evaluating a higher dose (1.1e14 gc/kg; n=2) in adult/older adolescent patients aged 15 or greater, and a pediatric cohort at a low dose level (6.7e13 gc/kg; n=2).” (opens the source at this quote in a new tab)

“Five patients [pediatric (n=2) and adult/adolescent (n=3)] were treated with the low dose (6.7 x 1013 GC/kg), and 2 adult/adolescent patients were treated with the high dose (1.1 x 1014 GC/kg).” (opens the source at this quote in a new tab)

Body weight and total vector dose by participant in the adult and adolescent cohorts

Participant	Age at treatment	Dosing weight	Cohort dose	Total dose
1001	“17 y”	“52.2 kg”	“6.7 x 1013 GC/kg”	“3.25 x 1015 GC”
1002	“20 y”	“89.1 kg”	“6.7 x 1013 GC/kg”	“5.97 x 1015 GC”
1005	“18 y”	“97.8 kg”	“6.7 x 1013 GC/kg”	“6.08 x 1015 GC”
1006	“21 y”	“82.7 kg”	“1.1 x 1014 GC/kg”	“9.10 x 1015 GC”
1007	“20 y”	“96.7 kg”	“1.1 x 1014 GC/kg”	“1.06 x 1016 GC”

Pediatric cohort dose with weight-based caps

“An enhanced immunosuppressive regimen incorporating rituximab, sirolimus and limited corticosteroids was implemented to minimize the risk of complement-mediated events and steroid exposure after a single IV infusion of RP-A501 (AAV9.LAMP2B) at 6.7 × 1013 GC/kg with weight-based viral titer caps.” (opens the source at this quote in a new tab)
“Two pediatric patients (ages 11 and 12y) have received IV RP-A501 (6.7 × 1013 GC/kg).” (opens the source at this quote in a new tab)

Discontinuation of the higher dose, August 2021

“In agreement with FDA, Rocket will no longer continue dosing patients at the higher dose (1.1e14).” (opens the source at this quote in a new tab)

Immunomodulation stated in the registry

“Prior to infusion of IP, rituximab and sirolimus will be administered prophylactically.” (opens the source at this quote in a new tab)

Immunomodulation summarized in the publication abstract

“All the patients received a transient immunomodulatory regimen of prednisone, tacrolimus or sirolimus, and rituximab.” (opens the source at this quote in a new tab)

Immunomodulation by cohort as presented in October 2026

Cohort	Participants and dose	Regimen
Cohort 1	“Adult/Adolescent (n=3) 6.7 x 1013 GC/kg RP-A501”	“IM regimen: Steroid (n=1); Steroid + Tacrolimus (n=2)”
Cohort 2	“Adult/Adolescent (n=2) 1.1 x 1014 GC/kg RP-A501”	“IM regimen: Rituximab + Steroid + Tacrolimus”
Cohort 1A	“Pediatric (n=2) 6.7 x 1013 GC/kg RP-A501”	“IM regimen: Rituximab + Steroid + Sirolimus”

Immunomodulation by participant in the low-dose adult and adolescent cohort as presented in December 2020

Participant	Regimen
1001	“Steroids only (limited compliance)”
1002	“Steroids only (local monitoring)”
1005	“Steroids → Tacrolimus”

Corticosteroids in all participants and added immunosuppression at the higher dose

“All patients were given oral steroids to prevent or minimize potential immune-related events.” (opens the source at this quote in a new tab)
“In the higher dose cohort (detailed immediately below), additional immunosuppressive therapies were stipulated and administered to mitigate the immune response associated with RP-A501.” (opens the source at this quote in a new tab)

Agents and doses by cohort as presented in May 2023

Cohort and agent	Regimen as shown
Cohort 1, low-dose adult (N=3): corticosteroid	“Steroid (prednisone 1mg/kg)”
Cohort 1, low-dose adult (N=3): calcineurin inhibitor	“Tacrolimus”
Cohort 2, high-dose adult (N=2): corticosteroid	“Steroid (prednisone 1mg/kg)”
Cohort 2, high-dose adult (N=2): calcineurin inhibitor	“Tacrolimus”
Cohort 2, high-dose adult (N=2): anti-CD20 antibody	“Rituximab (2 doses)”
Cohort 3, low-dose pediatric (N=2): corticosteroid	“Steroid (prednisone 0.5-0.8mg/kg): taper starting day 10”
Cohort 3, low-dose pediatric (N=2): mTOR inhibitor	“Sirolimus (target trough 4-8 ng/mL)”
Cohort 3, low-dose pediatric (N=2): anti-CD20 antibody	“Rituximab (2 doses)”

Changes to the regimen for the pediatric cohort

“Sirolimus to inhibit complement activation” (opens the source at this quote in a new tab)
“Steroid-sparing regimen to decrease skeletal myopathy” (opens the source at this quote in a new tab)
“Initial dose 0.5 to 0.8 mg/kg/day (compared to > 1mg/kg/day in adult cohort)” (opens the source at this quote in a new tab)
“Early initiation of taper (Day 10) and discontinuation (goal Month 3)” (opens the source at this quote in a new tab)

Monitoring of adherence to immunomodulation

“Patient 1001 was only locally monitored for compliance for two weeks; longer compliance monitoring initiated after 1001” (opens the source at this quote in a new tab)

“IM compliance was confirmed in 6/7 pts.” (opens the source at this quote in a new tab)

Duration of immunosuppression under the updated protocol

“with all immunosuppressive therapy discontinued 2-3 months following administration of RP-A501” (opens the source at this quote in a new tab)

Primary outcome measures in the registry

Outcome measure	Measure description	Time frame
“Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)”	“Evaluation of safety associated with RP-A501”	“3 years”
“Number of participants within each dose level cohort with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)”	“Assessment of safety at both doses (single IV administration)”	“3 years”
“Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy”	“Assessment of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy”	“3 years”
“Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing”	“Assessment of clinical stabilization of cardiomyopathy following infusion of RP-A501 via cardiopulmonary testing”	“3 years”

Secondary outcome measures in the registry

Outcome measure	Measure description	Time frame
“Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology”	“Evaluation of sustained improvement or stabilization in cardiovascular pathophysiology as assessed by medical evaluation, radiographic evaluation of cardiac structure and function, and cardiopulmonary exercise/physiologic parameters”	“3 years”
“Determination of the percentage of patients in whom cardiomyocytes corrected LAMP2B gene and/or protein”	“Evaluation of the percentage of patients in whom cardiomyocytes contain the corrected LAMP2B gene and/or protein and improvement in DD-associated histologic abnormalities and when feasible to quantify the extent of genetic and histologic correction in the myocardium.”	“3 years”
“Determination and characterization of immunologic response to RP-A501”	“Assessment of potential immunogenicity to the components of the investigational product”	“3 years”
“Determination of the percentage of patients who require and/or receive treatment for heart failure following RP-A501”	“Assessment of the percentage of patients who require and/or receive subsequent cardiac transplantation, left ventricular assist device (LVAD), implantable cardioverter-defibrillator or pacemaker placement, electrophysiologic ablative procedure for cardiac conduction aberrancy or subsequent hospitalizations for heart failure.”	“3 years”
“Evaluation of overall survival”	“Assessment of overall survival post RP-A501”	“3 years”

Primary, secondary, and exploratory outcomes in the publication abstract

“The primary outcomes were the safety and toxic effects of RP-A501, myocardial LAMP2 transduction and protein expression, stabilization of or reduction in heart-failure symptoms, and stabilization of or improvement in cardiac structure and function.” (opens the source at this quote in a new tab)
“Key secondary outcomes were sustained reduction in or stabilization of symptoms, immunologic response to RP-A501, end-stage heart failure, and overall survival.” (opens the source at this quote in a new tab)
“Exploratory outcomes included improvement in serologic markers of cardiac disease, patient-reported outcomes, and quality-of-life assessments.” (opens the source at this quote in a new tab)

Primary outcomes as listed in a sponsor presentation

“Early and long-term safety” (opens the source at this quote in a new tab)
“Target tissue transduction & LAMP2B protein expression” (opens the source at this quote in a new tab)
“Improved myocardial histology” (opens the source at this quote in a new tab)
“Clinical improvement or stabilization” (opens the source at this quote in a new tab)

Toxicities of systemic AAV9 administration anticipated by the investigators

“Acute complement-mediated thrombotic microangiopathy (TMA)” (opens the source at this quote in a new tab)
“Hepatotoxicity due to AAV liver accumulation and cell-mediated immunity” (opens the source at this quote in a new tab)
“Myocarditis” (opens the source at this quote in a new tab)
“Steroid-related skeletal myopathy” (opens the source at this quote in a new tab)

Adverse event coding and severity grading

“Based on MedDRA v23; the highest severity for each event (per NCI-CTCAE v.5.0) is presented.” (opens the source at this quote in a new tab)

Efficacy measure: myocardial LAMP2 protein expression on endomyocardial biopsy

“LAMP2 gene expression in endomyocardial biopsy samples is measured via both immunohistochemistry and Western blot and confirms the presence of LAMP2 protein in DD cardiac tissue following RP-A501 treatment.” (opens the source at this quote in a new tab)

“Grading of LAMP2 protein expression by IHC was done by a board-certified pathologist in a blinded fashion.” (opens the source at this quote in a new tab)
“The semi-quantitative grading reflects the extent of LAMP2 protein expressing cardiomyocytes in the entirety of biopsy sample according to the scale.” (opens the source at this quote in a new tab)

Immunohistochemistry staining grades for LAMP2 protein

Grade	Share of cardiomyocytes staining positive
Grade 0	“no staining”
Grade 1	“≤25%”
Grade 2	“26%–50%”
Grade 3	“51%–74%”
Grade 4	“≥75%”

Efficacy measure: histology and vacuolar area

“Histologic examination of endomyocardial biopsies via hematoxylin and eosin histology and electron microscopy is used to detect evidence of DD-associated tissue derangements, including the presence of autophagic vacuoles and disruption of myofibrillar architecture, each of which are characteristic of DD-related myocardial damage.” (opens the source at this quote in a new tab)

“Vacuolar area of endomyocardial tissue was quantified from H&E images. Data was quantified in a blinded manner using an AI tool.” (opens the source at this quote in a new tab)

Efficacy measure: left ventricular mass, mass index, and wall thickness

“Measurements of heart thickness, most notably, left ventricular mass and maximal left ventricular wall thickness, indicate the degree of hypertrophy present in the heart” (opens the source at this quote in a new tab)

“Centrally evaluated (blinded) MRI data were utilized for LVMI when available. All other measurements of cardiac structure and function reflect centrally evaluated (blinded) echocardiogram data.” (opens the source at this quote in a new tab)

Efficacy measure: troponin I and natriuretic peptides

“High sensitivity troponin I or hs-TnI and BNP are blood-based evaluations and a key marker of HF and cardiac injury. Both are frequently elevated in DD patients and have been shown to be markedly elevated in patients with advanced stage disease.” (opens the source at this quote in a new tab)

“Central laboratory assessment of cTnI was performed on cryopreserved and non-cryopreserved samples. Values for cTnI from high-sensitivity and earlier tests.” (opens the source at this quote in a new tab)

Efficacy measure: Kansas City Cardiomyopathy Questionnaire

“KCCQ is a validated, patient-reported quality-of-life assessment that measures a patient’s perception of their HF symptoms, impact of disease on physical and social function, and the impact of their HF on overall health status and quality of life.” (opens the source at this quote in a new tab)
“Assessment scores range from 0 (very poor health status) to 100 (excellent health status). Changes in KCCQ score of +/- 5 points are considered meaningful and have been shown to correlate with HF outcomes.” (opens the source at this quote in a new tab)

Efficacy measure: New York Heart Association functional class

“NYHA Functional Classification is the most commonly used HF classification system. NYHA Class I reflects the absence of clinical signs of HF, while NYHA Class II is where a patient exhibits a slight limitation of physical activity, is comfortable at rest, and ordinary physical activity results in fatigue, palpitation and/or dyspnea.” (opens the source at this quote in a new tab)
“NYHA Class III and IV are considered more severe or advanced HF.” (opens the source at this quote in a new tab)

Sponsor statement on why the efficacy assessments were collected

“We conducted a variety of efficacy assessments in the Phase 1 clinical study to measure the prospect of benefit for patients.” (opens the source at this quote in a new tab)

Planned number of participants

“During the course of the study, approximately 7-10 male subjects age 8 and over will receive a single intravenous (IV) infusion of the IP.” (opens the source at this quote in a new tab)
“Cohort 1: Adult and age 15-17: 6.7 × 1013 GC/kg (n=3-4)” (opens the source at this quote in a new tab)
“Cohort 1A: Pediatric age 8-14: 6.7 × 1013 GC/kg (n=2-4)” (opens the source at this quote in a new tab)

Actual enrollment in the registry

“Enrollment (Actual) 7” (opens the source at this quote in a new tab)

Seven participants treated

“RP-A501 infusion was administered to seven male patients with Danon disease: five who were 15 years of age or older and two who were between 11 and 14 years of age.” (opens the source at this quote in a new tab)

Six participants with normal ejection fraction at baseline in the efficacy results

“In the six patients with normal left ventricular ejection fraction at baseline, we observed cardiac LAMP2 protein expression and a reduction from baseline in or stabilization of the left ventricular mass index, preservation of left ventricular ejection fraction, and reduction in or stabilization of the levels of cardiac troponin I and N-terminal pro-B-type natriuretic peptide.” (opens the source at this quote in a new tab)

“Patient 5 had LV systolic dysfunction (LVEF <40%) at enrollment and had progressive heart failure requiring transplantation 5m following RP-A501 treatment and is not evaluable for efficacy.” (opens the source at this quote in a new tab)

One screen failure named in a sponsor presentation

“NHS: patients from prospective NHS (patients 3,4,6,7,8,9), natural history (DD53) and screen failure from Phase I study (1010).” (opens the source at this quote in a new tab)

Sample size justification

No evidence found.

Exclusion of the participant who underwent transplantation from efficacy displays

“This patient underwent heart transplant due to DD progression five months post RP-A501 infusion; both because this patient would no longer be eligible for future studies based on revised eligibility criteria and because long-term RP-A501 effect is not evaluable, data for this patient are not shown.” (opens the source at this quote in a new tab)

“At approximately 12 months, all six patients in the principal Phase 1 analysis demonstrated myocardial LAMP2 protein expression and at least a 10% reduction in left ventricular mass index.” (opens the source at this quote in a new tab)

Baseline definition and use of core laboratory data

“Pre-dose (baseline) value defined as the mean values from all visits prior to infusion” (opens the source at this quote in a new tab)
“Core lab data presented for echocardiographic parameters, cardiac serologies, and cardiac histology” (opens the source at this quote in a new tab)

Conventions for the most recent visit and the 12-month assessment in the July 2026 data extraction

“For Patient 1, NYHA class and KCCQ-12 assessments occurred at Month 84, and all other assessments at Month 72.” (opens the source at this quote in a new tab)
“For Patient 3, NYHA class assessment occurred within the Month 84 visit window, and all other assessments at Month 54.” (opens the source at this quote in a new tab)
“Utilized 18 m data when 12m assessment was not done.” (opens the source at this quote in a new tab)
“Reflects 9M visit biopsy as 12M biopsy not performed.” (opens the source at this quote in a new tab)
“Where possible, cardiac MRI assessments shown (patients 1, 4, and 7); otherwise, echocardiogram data presented.” (opens the source at this quote in a new tab)

Data cut dates of the reported results

“as of the cutoff date of November 2020” (opens the source at this quote in a new tab)

“data cut-off September 27, 2022 for pediatric patients, and August 19, 2022 for adult patients, with source data verification through July 11, 2022” (opens the source at this quote in a new tab)

“Data from the Phase 1 study (cut-off April 19, 2024)” (opens the source at this quote in a new tab)

“Data Extraction Date: July 31, 2026” (opens the source at this quote in a new tab)

Statistical analysis plan and hypothesis testing

No evidence found.

All seven participants alive at 24 to 54 months

“At 24 to 54 months, all the patients were alive, with complete resolution of side effects.” (opens the source at this quote in a new tab)

Heart transplantation 5 months after infusion in the participant with systolic dysfunction at baseline

“One patient with left ventricular systolic dysfunction at baseline had progressive heart failure and underwent transplantation 5 months after infusion.” (opens the source at this quote in a new tab)

“As previously announced, a patient receiving therapy on the high dose cohort (1.1e14 gc/kg dose) had progressive HF and underwent a heart transplant at month five following therapy.” (opens the source at this quote in a new tab)
“The patient’s clinical course was characteristic of DD progression. The patient is doing well post-transplant.” (opens the source at this quote in a new tab)

Clinical course before transplantation and findings in the explanted heart

“Baseline risk factors suggest "point of no return" in Danon disease progression” (opens the source at this quote in a new tab)
“Prior evidence of fibrosis on MRI” (opens the source at this quote in a new tab)
“Uncontrolled arrhythmias resulting in decompensated heart failure” (opens the source at this quote in a new tab)
“Heart transplant (Month 5)” (opens the source at this quote in a new tab)
“Danon Disease progression determined as primary cause” (opens the source at this quote in a new tab)

“This patient continued to have progressive disease considered unrelated to gene therapy by the trial investigator as well as his transplant cardiologist and successfully received a heart transplant.” (opens the source at this quote in a new tab)
“Analysis of the explanted heart demonstrated fibrosis that was consistent with end-stage Danon disease.” (opens the source at this quote in a new tab)

Baseline ejection fraction of the transplanted participant reported as 35% in 2021 and 2023

“This patient had advanced disease including diminished LV ejection fraction (35%) on echocardiogram and markedly elevated LV filling pressure prior to treatment.” (opens the source at this quote in a new tab)

“as evidenced by diminished baseline left ventricle (“LV”) ejection fraction (35%) on echocardiogram and markedly elevated LV filling pressure prior to treatment” (opens the source at this quote in a new tab)

Baseline ejection fraction of the transplanted participant reported as 32% in 2026

“This patient had more advanced disease than the four other adult/older adolescent patients who received treatment in the low and high dose cohorts, as evidenced by diminished baseline left ventricle ejection fraction (32%) on echocardiogram and markedly elevated left ventricle filling pressure prior to treatment.” (opens the source at this quote in a new tab)

Second heart transplantation, 4.8 years after infusion and after the July 31, 2026 data extraction

“Patient underwent heart transplant at 4.8 years post-RP-A501 infusion; post data cut.” (opens the source at this quote in a new tab)

Survival and follow-up duration at the July 31, 2026 data extraction

“100% overall survival; median transplant-free survival not reached at median follow-up: 5.7 years (range: 4.3–7.1 years)” (opens the source at this quote in a new tab)

Age and month of the most recent visit by participant at the July 31, 2026 data extraction

Participant	Cohort	Age at most recent visit (years)	Most recent visit (months)
1	Low dose, adult or adolescent	“24”	“84‡”
2	Low dose, adult or adolescent	“26”	“72”
3	Low dose, adult or adolescent	“23”	“54‡”
4	High dose, adult or adolescent	“23”	“36”
6	Low dose, pediatric	“15”	“36”
7	Low dose, pediatric	“14”	“36”

Follow-up durations at earlier data cuts

“All pts are alive and stable at 3-30 months (m) follow-up.” (opens the source at this quote in a new tab)

“Evidence of sustained clinically meaningful improvement was observed in pediatric patients followed up to 24 months and adult/adolescent patients followed up to 60 months.” (opens the source at this quote in a new tab)

Age and sex of the seven participants

“RP-A501 infusion was administered to seven male patients with Danon disease: five who were 15 years of age or older and two who were between 11 and 14 years of age.” (opens the source at this quote in a new tab)

“7 males with DD age 11.7 - 21.1y (median 18.3y; N=5 adult and N=2 pediatric)” (opens the source at this quote in a new tab)

Baseline characteristics by participant from core laboratory data (data cut-off July 11, 2022)

Participant	Cohort	Age at infusion (years)	NYHA class	LVEF (%)	Maximum LV wall thickness (mm)	LV mass (g)	BNP (pg/mL)	hsTnI (ng/mL)	KCCQ-12
1001	Low dose, adult or adolescent	“17.4”	“II”	“57”	“25”	“311”	“55”	“0.6”	“44”
1002	Low dose, adult or adolescent	“20.3”	“II”	“55”	“64”	“989”	“1308”	“1.46”	“64”
1005	Low dose, adult or adolescent	“18.3”	“II”	“65”	“33”	“438”	“166”	“0.28”	“77”
1006	High dose, adult or adolescent	“21.1”	“II”	“62”	“22”	“410”	“135”	“0.54”	“79”
1007	High dose, adult or adolescent	“20.7”	“II”	“32”	“27”	“966”	“651”	“2.59”	“67”
1008	Low dose, pediatric	“12.3”	“II”	“74”	“42”	“605”	“1837”	“1.89”	“50”
1009	Low dose, pediatric	“11.7”	“II”	“77”	“19”	“234”	“297”	“0.67”	“52”

“Patients had marked left ventricular hypertrophy with elevated BNP and troponins at baseline” (opens the source at this quote in a new tab)

Baseline status of the adult and adolescent participants from local site assessment, presented in November 2021

Participant	Age at enrollment	Weight (kg)	NYHA class	Six-minute walk (meters)	BNP (pg/mL)	LV posterior wall thickness in diastole (mm)	LVEF (%)	Pulmonary capillary wedge pressure (mmHg)
1001	“17 years”	“52.2”	“II”	“443”	“70”	“16.4”	“62”	“11”
1002	“20 years”	“89.1”	“II”	“405”	“1104”	“22.4”	“59”	“19”
1005	“18 years”	“91.8”	“II”	“427”	“161”	“17”	“59”	“13”
1006	“21 years”	“82.7”	“II”	“436”	“123”	“15”	“47”	“14”
1007	“20 years”	“96.7”	“II”	“434”	“630”	“22.7”	“35”	“26”

“All echocardiographic parameters from local site assessment: LVEF=left ventricular ejection fraction” (opens the source at this quote in a new tab)

Baseline status of the two pediatric participants

Characteristic	Participant 1008	Participant 1009
Age at infusion	“Age at infusion: 12.3 years”	“Age at infusion: 11.7 years”
Maximum LV wall thickness	“Max LV wall thickness: 41.9 mm”	“Max LV wall thickness: 19.8 mm”
Wall thickness z-score	“z-score: +32”	“z-score: +12”
Implantable cardioverter-defibrillator	“ICD: yes”	“ICD: no”
Wolff-Parkinson-White syndrome	“WPW: yes”	“WPW: no”
Six-minute walk test	“6MWT: 437 meters”	“6MWT: 553 meters”

“Recommended prior to enrollment; ICD implanted 3 months after RP-A501” (opens the source at this quote in a new tab)

Functional class at baseline: one participant in class III in a congress abstract

“83% of pts were NYHA Class II; one was NYHA Class III.” (opens the source at this quote in a new tab)

LAMP2 expression on baseline endomyocardial biopsy

“On baseline endomyocardial biopsy, no pts had significant LAMP2B expression” (opens the source at this quote in a new tab)

Pre-existing anti-AAV9 immunity in the participant who later had thrombotic microangiopathy

“one of the two treated patients, who received the higher absolute AAV9 dose and had some degree of pre-existing anti-AAV9 immunity” (opens the source at this quote in a new tab)

Race and ethnicity

No evidence found.

Efficacy findings in the publication abstract (24 to 54 months)

“In the six patients with normal left ventricular ejection fraction at baseline, we observed cardiac LAMP2 protein expression and a reduction from baseline in or stabilization of the left ventricular mass index, preservation of left ventricular ejection fraction, and reduction in or stabilization of the levels of cardiac troponin I and N-terminal pro-B-type natriuretic peptide.” (opens the source at this quote in a new tab)
“A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a period of 24 to 54 months.” (opens the source at this quote in a new tab)

Left ventricular mass index and wall thickness: change from baseline to most recent visit by participant (data extraction July 31, 2026)

Participant	Cohort	Most recent visit (months)	LVMI (g/m^2.7)	Interventricular septum in diastole (mm)	LV posterior wall in diastole (mm)
1	Low dose, adult or adolescent	“84‡”	“-32%, 85.0 to 57.8”	“+2%, 19.8 to 20.2”	“-30%, 18.8 to 13.2”
2	Low dose, adult or adolescent	“72”	“-31%, 260.2 to 178.9”	“-29%, 60.1 to 42.6”	“-71%, 39.1 to 11.3”
3	Low dose, adult or adolescent	“54‡”	“-12%, 98.2 to 86.7”	“-30%, 30.9 to 21.7”	“-56%, 32.1 to 14.1”
4	High dose, adult or adolescent	“36”	“-7%, 68.6 to 63.6”	“+5%, 18.0 to 19.0”	“-27%, 24.0 to 17.4”
6	Low dose, pediatric	“36”	“-47%, 141.5 to 74.7”	“-32%, 42.4 to 29.0”	“-2%, 22.8 to 22.3”
7	Low dose, pediatric	“36”	“+3%, 82.0 to 84.9”	“+13%, 18.5 to 20.9”	“+66%, 14.9 to 24.7”

NT-proBNP and cardiac troponin I: change from baseline to most recent visit by participant (data extraction July 31, 2026)

Participant	Cohort	Most recent visit (months)	NT-proBNP (ng/L)	Cardiac troponin I (ng/mL)
1	Low dose, adult or adolescent	“84‡”	“-31%, 336 to 233”	“-99%, 0.60 to 0.01”
2	Low dose, adult or adolescent	“72”	“-90%, 5119 to 489”	“-96%, 1.46 to 0.06”
3	Low dose, adult or adolescent	“54‡”	“-45%, 841 to 460”	“-76%, 0.28 to 0.07”
4	High dose, adult or adolescent	“36”	“-65%, 720 to 249”	“-39%, 0.47 to 0.29”
6	Low dose, pediatric	“36”	“-75%, 1629 to 406”	“-84%, 1.78 to 0.28”
7	Low dose, pediatric	“36”	“-35%, 1912 to 1238”	“-31%, 1.08 to 0.74”

Left ventricular mass index: change from baseline at about 12 months by participant (data extraction July 31, 2026)

Participant	Assessment used	LVMI change from baseline
1	Month 12	“-16%”
2	Month 18	“-14%”
3	Month 18	“-18%”
4	Month 12	“-11%”
6	Month 12	“-32%”
7	Month 12	“-15%”

Phase 1 results measured against the co-primary endpoint criteria of the pivotal trial (data extraction July 31, 2026)

“All patients showed ≥10% LVMI decrease and LAMP2 protein expression increase (≥ Grade 1) at ~12m, representing 100% response rate based on pivotal Ph 2 endpoints” (opens the source at this quote in a new tab)
“All patients showed durable myocardial LAMP2 protein expression and improved or sustained LVMI at most recent visit” (opens the source at this quote in a new tab)

Left ventricular mass index at three to seven years: below baseline in five of six participants

“At follow-up of approximately three to seven years, left ventricular mass index was below baseline in five of six patients, with reductions of at least 10% in four patients.” (opens the source at this quote in a new tab)
“All six patients also had sustained reduction of cardiac biomarkers and improvements of quality of life.” (opens the source at this quote in a new tab)

Myocardial LAMP2 protein expression to 60 months (data extraction July 31, 2026)

“Durable myocardial LAMP2 protein expression seen in all patients” (opens the source at this quote in a new tab)
“Grade 0 LAMP2 protein IHC staining at the 30- and 36-month assessments, however, LAMP2B vector RNA and DNA (VCN) levels have persisted through 60 months of follow-up” (opens the source at this quote in a new tab)

Comparison with untreated males in the International Danon Disease Registry (data extraction July 31, 2026)

Measure	Annual change in untreated males	Registry patients in the regression	Coefficient of determination
BNP	“BNP increases by 42.17 ± 18.46 pg/mL per year in untreated Danon males”	“N = 20 patients”	“r2= 0.246”
LV mass	“LV Mass increases by 39.86 ± 4.01 g per year in untreated Danon males”	“N = 22 patients”	“r2= 0.846”

“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)
“Differs significantly from expanded natural history data” (opens the source at this quote in a new tab)

LAMP2 expression and left ventricular mass index at 12 months and their persistence (data cut-off April 19, 2024)

“all evaluable Danon disease patients demonstrated LAMP2 protein expression at 12 months (sustained up to 60 months) and reduction of left ventricular (LV) mass index by ≥10% at 12 months (sustained up to 54 months) after treatment” (opens the source at this quote in a new tab)
“Preliminary long-term follow-up assessments for Patient 1001 were positive for immunohistochemical staining and appear to show Grade 3 expression in the heart at the five-year timepoint.” (opens the source at this quote in a new tab)

Median changes in left ventricular mass index, troponin I, and NT-proBNP (data cut-off April 19, 2024)

“Reduction or stabilization of LV mass index – the median reduction from baseline to most recent visit of 24% (for the ongoing pivotal Phase 2 trial, a 10% reduction in LV mass index and positive protein expression of Grade 1 or more are co-primary endpoints);” (opens the source at this quote in a new tab)
“Preservation of normal LV ejection fraction (LVEF);” (opens the source at this quote in a new tab)
“Reduction or stabilization of cardiac biomarkers (median cTnI and NTproBNP reductions of 84% and 57%, respectively);” (opens the source at this quote in a new tab)

The 57% median reduction attributed to BNP in the annual report

“Reduction or stabilization of cardiac biomarkers (median cardiac troponin I [cTnI] and BNP reductions of 84% and 57%, respectively);” (opens the source at this quote in a new tab)

Troponin I, BNP, left ventricular mass, and wall thickness: baseline to most recent visit by participant (data cut-off July 11, 2022)

Participant	Cohort	Follow-up (months)	hsTnI (ng/mL)	BNP (pg/mL)	LV mass (g)	Maximum LV wall thickness (mm)
1001	Low dose, adult or adolescent	“36”	“0.6 ⇢ 0.01”	“55 ⇢ 59”	“311 ⇢ 212”	“25 ⇢ 23”
1002	Low dose, adult or adolescent	“36”	“1.46 ⇢ 0.06”	“1308 ⇢ 80”	“989 ⇢ 511”	“64 ⇢ 38”
1005	Low dose, adult or adolescent	“30”	“0.28 ⇢ 0.15”	“166 ⇢ 176”	“438 ⇢ 375”	“33 ⇢ 24”
1006	High dose, adult or adolescent	“24”	“0.54 ⇢ 0.20”	“135 ⇢ 42”	“410 ⇢ 300”	“22 ⇢ 18”
1008	Low dose, pediatric	“12”	“1.89 ⇢ 0.26”	“1837 ⇢ 306”	“605 ⇢ 432 (M9)”	“42 ⇢ 36 (M9)”
1009	Low dose, pediatric	“6”	“0.67 ⇢ 0.07”	“297 ⇢ 113”	“234 ⇢ 185”	“20 ⇢ 20”

“Does not include pt 1007 in Ph1 trial who had advanced HF with EF<40% at enrollment and received HTx 5M following tx due to pre-existing advanced HF.” (opens the source at this quote in a new tab)

Vacuolar area on endomyocardial biopsy (data cut-off September 27, 2022)

“In the first pediatric patient, vacuolar area as assessed by an automated method in representative biopsy samples was found to have decreased by 77% at six months.” (opens the source at this quote in a new tab)
“All adult patients showed meaningful decreases in vacuolar area ranging from 26% to 74% at most recent available timepoints.” (opens the source at this quote in a new tab)

Early results in the pediatric cohort at 3 to 9 months (data cut-off September 27, 2022)

“In the pediatric cohort, LAMP2B gene expression by immunohistochemistry was 21.1% in patient 1008 at six months and 34.7% in patient 1009 at three months.” (opens the source at this quote in a new tab)
“In the pediatric cohort, BNP, a key marker of heart failure, decreased from a pretreatment baseline by 78% in patient 1008 at nine months and by 62% in patient 1009 at six months.” (opens the source at this quote in a new tab)
“The pediatric patients, despite a more limited six and nine months of follow-up, were observed to have meaningful decreases in high sensitivity troponin I (hsTnI), a protein in the blood showing signs of cardiac injury, of 90% and 85%, respectively.” (opens the source at this quote in a new tab)
“In the pediatric cohort, patient 1008 demonstrated reduction in maximum LV wall thickness by 3% from treatment baseline after six months of follow-up.” (opens the source at this quote in a new tab)

Wall thickness in the adult and adolescent cohorts at 18 to 24 months (data cut-off August 19, 2022)

“In the adult cohort, three patients demonstrated a reduction of greater than 15% and greater than 15% from mean baseline in both LV posterior wall thickness in diastole and maximum LV wall thickness, respectively, compared to mean values at 18 to 24 months, which represents improvement of the ventricular hypertrophy.” (opens the source at this quote in a new tab)

Counts of evaluable participants with stabilized or improved measures up to 30 months

“100% (N=6/6) of evaluable pts had cardiac LAMP2B expression within 6m of therapy with improved myocardial structure in 5/6.” (opens the source at this quote in a new tab)
“Pts evaluable beyond 6m had stabilized or improved BNP (N=5/5), troponin (N=5/5), and LV ejection fraction (N=5/5) by 6-12m, and stabilized/improved LV wall thickness (N=4/4) and NYHA Class (N=4/4) by 12-18m.” (opens the source at this quote in a new tab)
“These findings persist up to 30m post RP-A501.” (opens the source at this quote in a new tab)

Cardiac vector copy number by quantitative PCR, presented in September 2022

Participant	Sample	Vector copies per diploid nucleus
1001	Month 6	“0.384”
1001	Month 12	“0.197”
1001	Month 36	“0.120”
1002	Month 12	“0.575”
1002	Month 30	“0.590”
1005	Month 6	“0.583”
1005	Month 30	“1.228”
1006	Month 6	“2.693”
1006	Month 12	“1.131”
1007	Explanted heart at 5 months, right ventricle	“RV: 6.77”
1007	Explanted heart at 5 months, left ventricle	“LV: 9.15”
1008	Month 6	“0.492”

“Cardiac LAMP2 DNA by qPCR (vector copies per diploid nucleus)” (opens the source at this quote in a new tab)
“Assessment from explanted heart tissue at 5 months.” (opens the source at this quote in a new tab)
“Month 30 visit.” (opens the source at this quote in a new tab)

Cardiac vector copy number as presented in November 2021

Participant	Week 8	Later sample	Time of later sample
1001	“0.5”	“0.6”	“Month 12”
1002	“6.5”	“1.5”	“Month 12”
1005	“2.5”	“1.9”	“Month 9 data”
1006	“3.9”	“1.1”	“Month 12”
1007, right ventricle	“5.9”	“6.8 (RV)”	“Explanted heart samples at Month 5”
1007, left ventricle	“5.9”	“9.2 (LV)”	“Explanted heart samples at Month 5”

LAMP2B protein by quantified immunohistochemistry as presented in November 2021

Participant	Week 8	Later sample	Time of later sample
1001	“7.3%”	“2.5% (Previously <15%)”	“Month 12”
1002	“36.9%”	“67.8%”	“Month 12”
1005	“17.6%”	“92.4%”	“Month 9 data”
1006	“5.0%”	“100%”	“Month 12”
1007	“6.9%”	“100%”	“Explant sample at Month 5”

“Endomyocardial biopsies stained for LAMP2 compared to normal control samples. Percent area of cell staining was quantitated using software in a blinded fashion from 2 to 14 sections.” (opens the source at this quote in a new tab)

A different immunohistochemistry value for participant 1002 reported in May 2021

“Patient 1002: 78% IHC (revised from previous 67% due to improved technique), BNP continues to decrease to 200 (baseline 943)” (opens the source at this quote in a new tab)

LAMP2B protein by Western blot as presented in November 2021

Participant	Week 8	Month 5 to 18	Time point of the later sample
1001	“20.7%”	“17.9%”	“Month 6 data; inadequate sample at Month 12”
1002	“27.3%”	“21.2%”	“Month 18 data; inadequate sample at Month 12”
1005	“42.8%”	“61.1%”	“Month 9 data”
1006	“14.6%”	“18.2%”	“Month 6 data; inadequate sample at Month 12”
1007, right ventricle	“25.0%”	“RV: 45.1%”	“Explanted heart; Month 5 data”
1007, left ventricle	“25.0%”	“LV: 44.0%”	“Explanted heart; Month 5 data”

LAMP2B expression in the explanted heart 5 months after infusion

“Myocardial tissue from the explanted heart at 5 months post-treatment displayed 100% LAMP2B protein expression by immunohistochemistry throughout non-fibrotic cardiac regions including the ventricles and other essential targeted areas.” (opens the source at this quote in a new tab)
“Analysis of the explanted heart revealed significant fibrosis consistent with advanced Danon Disease.” (opens the source at this quote in a new tab)

BNP and six-minute walk distance in the adult and adolescent cohorts at 12 to 24 months, presented in November 2021

Participant	Time of follow-up	BNP at baseline (pg/mL)	BNP at follow-up (pg/mL)	Six-minute walk at baseline (meters)	Six-minute walk at follow-up (meters)
1001	“24 months”	“70”	“30”	“443”	“467”
1002	“18 months”	“942”	“200”	“405”	“410”
1005	“15 months”	“176”	“44”	“427”	“435”
1006	“12 months”	“123”	“41”	“436”	“492”

Wall thickness, ejection fraction, and hemodynamics at 12 to 18 months, announced in November 2021

“In patients with closely monitored immunosuppression (two low-dose and one high-dose) left ventricular (LV) posterior wall thickness improved (average 23% decrease compared to pretreatment baseline) and ejection fraction improved or stabilized (average 20% increase compared to pretreatment baseline) at 12 to 18 months on echocardiography.” (opens the source at this quote in a new tab)
“Cardiac output remained normal for all patients with improved or stable left heart filling pressures as measured by cardiac catheterization.” (opens the source at this quote in a new tab)

First results in the low-dose cohort (data cut-off November 2020)

“From the perspective of gene expression results, all three low dose patients demonstrated evidence of cardiac LAMP2B expression by Western blot and/or immunohistochemistry.” (opens the source at this quote in a new tab)
“Brain natriuretic peptide, a key marker of heart failure, improved in all three patients, including by greater than 50% in the two patients with closely monitored immunosuppressive regimen compliance.” (opens the source at this quote in a new tab)
“Additionally, two of the three low dose patients with closely monitored immunosuppressive regimen compliance demonstrated improvement in cardiac output as measured by invasive hemodynamics, including one patient who showed a 1.62-fold improvement in cardiac output at month 12, and one patient who showed a 1.35-fold improvement at month 9.” (opens the source at this quote in a new tab)
“For the patient with the apparent inconsistent immunosuppressive regimen compliance, the cardiac output was lower at month 12 than at baseline.” (opens the source at this quote in a new tab)

Lower expression in the first participant, attributed by the sponsor to inconsistent immunosuppression (data cut-off November 2020)

“Although we did observe evidence of cardiac LAMP2B expression of approximately 15% of cells compared to normal as determined by immunohistochemistry at 12 months in this patient, we believe that such expression was likely limited by inconsistent compliance with the immunosuppressive regimen, as evidenced by transient increases in transaminase levels approximately one month after treatment and a lack of adverse events frequently associated with the immunosuppressive regimen.” (opens the source at this quote in a new tab)

Low-dose cohort results in the 2021 congress abstract

“The two pts in Cohort 1 with observed immunosuppressive regimen compliance had high cardiac LAMP2B expression: 67.8% and 92.4% vs. normal control by IHC; up to 61% by WB.” (opens the source at this quote in a new tab)
“NPs were reduced by 59% and 42% at 9 and 12 months, respectively.” (opens the source at this quote in a new tab)
“All 3 pts had similar or mildly improved 6MWT, improved myocardial EM morphology with decreased autophagic vacuoles, improved/stabilized GLS and reported increases in physical activity.” (opens the source at this quote in a new tab)

Natriuretic peptides in trial participants and in a natural history cohort, presented in May 2023

“Natriuretic peptides improved or stabilized in Phase 1 compared to progressive increases in the NHS” (opens the source at this quote in a new tab)
“Phase 1 Trial (n=6) Natural History Study (n=8)” (opens the source at this quote in a new tab)
“NHS: patients from prospective NHS (patients 3,4,6,7,8,9), natural history (DD53) and screen failure from Phase I study (1010).” (opens the source at this quote in a new tab)

Natural history patients who later entered the trial, presented in May 2023

“#7: Entered Ph1 Trial (1005)” (opens the source at this quote in a new tab)
“#3: Entered Ph1 Trial 8M following this visit (1008)” (opens the source at this quote in a new tab)
“#9: Entered Ph1 Trial (1007*)” (opens the source at this quote in a new tab)

NYHA class and KCCQ-12 score: baseline to most recent visit by participant (data extraction July 31, 2026)

Participant	Cohort	Most recent visit (months)	NYHA class	KCCQ-12
1	Low dose, adult or adolescent	“84‡”	“II to I”	“+56, 44 to 100”
2	Low dose, adult or adolescent	“72”	“II to I”	“+24, 64 to 88”
3	Low dose, adult or adolescent	“54‡”	“II to II”	“+7, 77 to 84”
4	High dose, adult or adolescent	“36”	“II to I”	“+9, 79 to 89”
6	Low dose, pediatric	“36”	“II to I”	“+13, 50 to 63”
7	Low dose, pediatric	“36”	“II to I”	“+36, 52 to 88”

“For Patient 1, NYHA class and KCCQ-12 assessments occurred at Month 84, and all other assessments at Month 72.” (opens the source at this quote in a new tab)
“For Patient 3, NYHA class assessment occurred within the Month 84 visit window, and all other assessments at Month 54.” (opens the source at this quote in a new tab)

NYHA class and KCCQ at the most recent visit (data cut-off April 19, 2024)

“Improvement in New York Heart Association class from Class II at baseline to Class I at most recent follow-up visit; NYHA Class I reflects the absence of clinical signs of heart failure;” (opens the source at this quote in a new tab)
“Improvements in Kansas City Cardiomyopathy Questionnaire quality-of-life (median improvement of 27 points) scores that persisted up to 54 months of follow-up;” (opens the source at this quote in a new tab)

Change in KCCQ score considered meaningful by the sponsor

“Changes in KCCQ score of +/- 5 points are considered meaningful and have been shown to correlate with HF outcomes.” (opens the source at this quote in a new tab)

NYHA class at baseline, month 12, and the most recent visit by participant (data cut-off September 27, 2022)

Participant	Cohort	Baseline	Month 12	Most recent follow-up	Time of follow-up
1001	Low dose, adult	“II”	“II”	“II”	“36 months”
1002	Low dose, adult	“II”	“III”	“I”	“30 months”
1005	Low dose, adult	“II”	“II”	“I”	“30 months”
1006	High dose, adult	“II”	“I”	“I”	“24 months”
1008	Low dose, pediatric	“II”	“October 2022”	“I”	“9 months”
1009	Low dose, pediatric	“II”	“March 2023”	“I”	“6 months”

KCCQ score: baseline to most recent visit by participant (data cut-off July 11, 2022)

Participant	Cohort	Follow-up (months)	KCCQ score
1001	Low dose, adult or adolescent	“36”	“44 ⇢ 49”
1002	Low dose, adult or adolescent	“36”	“64 ⇢ 81”
1005	Low dose, adult or adolescent	“30”	“77 ⇢ 85 (M24)”
1006	High dose, adult or adolescent	“24”	“79 ⇢ 82”
1008	Low dose, pediatric	“12”	“50 ⇢ 82”
1009	Low dose, pediatric	“6”	“52 ⇢ 78”

KCCQ overall score in the pediatric cohort at 3 and 9 months (data cut-off September 27, 2022)

“Specifically, patient 1008 demonstrated improvement from a pretreatment baseline of 50 to 93 at nine months and patient 1009 demonstrated improvement from a pretreatment baseline of 52 to 81 at three months.” (opens the source at this quote in a new tab)
“All patients treated in pediatric and adult cohorts with a closely monitored immunomodulatory regimen showed improvements ranging between three and 43 points when comparing baseline to the most recent available timepoint.” (opens the source at this quote in a new tab)

NYHA class in the adult and adolescent cohorts by immunomodulation monitoring (data cut-off August 19, 2022)

“In the adult cohorts, all three patients treated with a closely monitored immunomodulatory regimen showed improvement in NYHA class. Stabilization of NYHA class was observed in one adult patient treated at the low dose without a closely monitored regimen.” (opens the source at this quote in a new tab)

Safety findings in the publication abstract (24 to 54 months)

“One patient had complement-mediated thrombotic microangiopathy (grade 4) with thrombocytopenia and acute kidney injury.” (opens the source at this quote in a new tab)
“Three patients had glucocorticoid-related exacerbation (grade 3) of Danon disease-related skeletal myopathy.” (opens the source at this quote in a new tab)
“At 24 to 54 months, all the patients were alive, with complete resolution of side effects.” (opens the source at this quote in a new tab)

Severity, relatedness, and reversibility of adverse events (data cut-off April 19, 2024)

“Most adverse events (AEs) were mild or moderate in severity, assessed as not related to RP-A501, and non-serious.” (opens the source at this quote in a new tab)
“All RP-A501 or immunomodulatory regimen-related AEs were manageable or reversible.” (opens the source at this quote in a new tab)

Grade 3 and 4 serious adverse events in the adult and adolescent cohorts by attribution, presented in May 2022

Attribution on the slide	Event and grade	Count, outcome, or participant note
“RP-A501 Related”	“Thrombotic microangiopathy (TMA) [grade 4]”	“Resolved fully with eculizumab and temporary hemodialysis”
“RP-A501 Related”	“thrombocytopenia [grade 4]”	“Resolved fully with eculizumab and temporary hemodialysis”
“RP-A501 Related”	“acute kidney injury & renal failure [grade 4]”	“Resolved fully with eculizumab and temporary hemodialysis”
“RP-A501 Related”	“Transaminase increase [grade 3]”	“n=3; transient and resolved with immunosuppression”
“Corticosteroid Related”	“Skeletal myopathy [grade 3]”	“n=3; resolved with steroid taper”
“Corticosteroid Related”	“Salmonella sepsis [grade 3]”	“n=1; resolved with antibiotics”
“Danon Disease Progression Likely Related”	“Acute cardiac failure with ventricular arrhythmia [grade 4]”	“Pt 1007 (LVEF 35% at enrollment)”

“Indicates events for which the relationship was definitely, probably, or possibly related.” (opens the source at this quote in a new tab)
“Pt 1007 (received highest dose secondary to baseline weight and 1.1 x 1014 GC/kg dose level)” (opens the source at this quote in a new tab)

Thrombotic microangiopathy at the higher dose: first report (data cut-off November 2020)

“At the higher dose administered (1.1×1014 gc/kg), one of the two treated patients, who received the higher absolute AAV9 dose and had some degree of pre-existing anti-AAV9 immunity, experienced a non-persistent, immune-related event that was classified as a drug product-related serious adverse event.” (opens the source at this quote in a new tab)
“This was believed to be likely due to complement activation, resulting in reversible thrombocytopenia and acute kidney injury requiring ecumizumab and transient hemodialysis.” (opens the source at this quote in a new tab)
“This patient returned to baseline within three weeks and regained normal kidney function.” (opens the source at this quote in a new tab)

“Patient with enhanced risk due to high weight & vector dose and pre-existing AAV immunity” (opens the source at this quote in a new tab)
“Anticipated SAE of atypical hemolytic-uremic syndrome (aHUS) resulting in reversible thrombocytopenia and acute kidney injury (AKI)” (opens the source at this quote in a new tab)
“AKI required supportive care including eculizumab and transient hemodialysis with full return to baseline kidney function within 2-3 weeks” (opens the source at this quote in a new tab)

Thrombotic microangiopathy: reclassification, dose relationship, and relation to the later transplantation

“No new drug-related safety events were observed in the low- or higher-dose adult cohorts; the previously disclosed SAE of thrombotic microangiopathy, which has since resolved, was reclassified as a SUSAR.” (opens the source at this quote in a new tab)

“This patient received the highest absolute dose secondary to high baseline weight and the higher (1.1e14 gc/kg) dose level.” (opens the source at this quote in a new tab)
“The TMA resolved fully with supportive therapy and the patient regained normal kidney function within three weeks.” (opens the source at this quote in a new tab)
“The patient’s progression to heart transplant is not associated with this event, but instead due to advanced DD at the time of treatment.” (opens the source at this quote in a new tab)

“RP-A501 r-AAV dose-dependent toxicity was seen at 1.1x1014 GC/kg dose levels” (opens the source at this quote in a new tab)
“Largest patient in clinical trial (>90kg) who received highest total dose (1.06 x 1016 GC)” (opens the source at this quote in a new tab)
“Baseline LV systolic failure may have contributed” (opens the source at this quote in a new tab)

Adverse events in the high-dose adult and adolescent cohort (n=2), presented in November 2021

Timing	Event	Participants
Immediate	Fever	“1”
Immediate	Fatigue	“2”
Immediate	Constipation	“1”
Immediate	Nausea or vomiting	“1”
Early	Complement activation	“1”
Early	Thrombocytopenia	“2”
Early	Transaminase elevation	“2”
Early	D-dimer elevation	“1”
Early	Thrombotic microangiopathy with acute kidney injury (red font)	“1”
Delayed	Transaminase elevation	“1”
Delayed	Deep vein thrombosis (red font)	“1”
Delayed	Steroid-induced myopathy (red font)	“1”
Delayed	Ventricular arrhythmias (red font)	“1”
Delayed	Acute heart failure (red font)	“1”

“Red colored font indicates Serious Adverse Event (SAE)” (opens the source at this quote in a new tab)
“Patient developed thrombotic microangiopathy (TMA) with acute renal failure requiring transient hemodialysis with complete renal function recovery” (opens the source at this quote in a new tab)
“All Grade 1, except for Grade 4 in patient who developed TMA” (opens the source at this quote in a new tab)

Adverse events in the low-dose adult and adolescent cohort (n=3), presented in November 2021

Timing	Event	Participants
Immediate	Fever	“1”
Immediate	Fatigue	“1”
Immediate	Constipation	“2”
Immediate	Nausea or vomiting	“3”
Early	Complement activation (not monitored in the initial participant)	“2”
Early	Thrombocytopenia	“2”
Early	Transaminase elevation	“3”
Early	D-dimer elevation	“3”
Delayed	Transaminase elevation	“2”
Delayed	Steroid-induced myopathy (red font)	“2”
Delayed	Salmonella sepsis (red font)	“1”

“Not monitored for in initial patient” (opens the source at this quote in a new tab)
“RP-A501 was well tolerated and all adverse events in low & high dose adult/adolescent cohorts were reversible demonstrating a manageable safety profile” (opens the source at this quote in a new tab)

Transaminase elevation and platelet decline in the low-dose adult and adolescent cohort

“No unexpected and serious drug product-related adverse events or severe adverse events were observed.” (opens the source at this quote in a new tab)
“The most common adverse events were mild and were related to elevated transaminases post treatment.” (opens the source at this quote in a new tab)
“Elevation in transaminases was observed in all three low-dose patients and returned to baseline within the first one to two months post-treatment.” (opens the source at this quote in a new tab)
“There was also a transient and reversible decline in platelets observed in these three patients.” (opens the source at this quote in a new tab)
“These changes were largely responsive to corticosteroids and other immunosuppressive therapies.” (opens the source at this quote in a new tab)

Platelet counts by cohort

Cohort	Platelet finding
Low dose, adult	“2 of 3 patients had platelet decreases to LLN range”
High dose, adult	“1 of 2 patients (Pt 1007) had grade 4 thrombocytopenia (transient)”
Low dose, pediatric	“2 of 2 patients had platelets remain within normal range”

Steroid-associated exacerbation of skeletal myopathy

“Across both dose levels, the most common serious adverse event (SAE) observed was steroid-induced myopathy in three patients (two low-dose and one high-dose) which resolved subsequent to corticosteroid discontinuation.” (opens the source at this quote in a new tab)

“Two patients in the low dose cohort and one patient in the high dose cohort experienced skeletal myopathy related to corticosteroid administration, which resolved with steroid taper.” (opens the source at this quote in a new tab)

Adverse events in the first five participants in the 2021 congress abstract

“Adverse events were mostly manageable with transient immunosuppression.” (opens the source at this quote in a new tab)
“Reversible platelet decreases and transaminase elevations that returned to baseline within 2 months were seen.” (opens the source at this quote in a new tab)
“One patient treated with 1.1 x 1014 GC/kg had complement-mediated thrombocytopenia and acute kidney injury requiring transient hemodialysis that fully recovered.” (opens the source at this quote in a new tab)
“An exacerbation of skeletal myopathy in 3 of the 5 patients resolved with steroid taper.” (opens the source at this quote in a new tab)

Timing of serious adverse events after infusion

“All SAEs observed within initial 2-4 months following dosing; reversible with supportive care” (opens the source at this quote in a new tab)
“No additional SAEs observed following initial 2-4 months” (opens the source at this quote in a new tab)

“Across the adult/older adolescent patients, no additional SAEs were observed following the first 2-4 months from treatment and all treatment-related adverse events were reversible with no lasting renal, hepatic or other sequelae.” (opens the source at this quote in a new tab)

Pediatric cohort: platelets, complement, renal, hepatic, and troponin findings after infusion

“Platelet counts remained within normal range with modest decreases during days 6-14 post-infusion.” (opens the source at this quote in a new tab)
“Complement soluble membrane attack complex (sC5b-9) increased during days 5-14 post-infusion; no increases >200ng/mL over any 24 hour period were observed; peak values remained <450ng/mL (ULN 250 ng/mL) and were markedly lower than those observed in the adult cohort.” (opens the source at this quote in a new tab)
“Hemoglobin and creatinine levels remained stable during the initial weeks post-infusion.” (opens the source at this quote in a new tab)
“Transaminases and liver-focused parameters (GGT and bilirubin) were also largely stable.” (opens the source at this quote in a new tab)
“Limited and transient troponin increases were noted, consistent with known AAV9 cardiotropism.” (opens the source at this quote in a new tab)
“Managed with a steroid-sparing regimen, steroid induced exacerbations of DD-related skeletal myopathy in the pediatric patients were limited relative to those reported in the adult cohort.” (opens the source at this quote in a new tab)

Pediatric cohort: no treatment-related serious adverse events at 6 and 11 months (data cut-off September 27, 2022)

“No treatment-related SAEs” (opens the source at this quote in a new tab)
“All AEs were Transient and Reversible with 6 and 11 month follow up in 1008 and 1009, respectively” (opens the source at this quote in a new tab)
“No complement-related clinical or laboratory AEs” (opens the source at this quote in a new tab)
“No reported skeletal myopathy or late transaminitis with initial steroid dose-reduction and more rapid taper, and introduction of sirolimus” (opens the source at this quote in a new tab)

“No RP-A501-related SAEs were observed in the pediatric pts.” (opens the source at this quote in a new tab)

Antibody responses to the vector

“Increases in neutralizing and anti-capsid antibodies were observed and were more modest than those in the adult cohort.” (opens the source at this quote in a new tab)

Deaths and heart transplantations through the July 31, 2026 data extraction

“100% overall survival; median transplant-free survival not reached at median follow-up: 5.7 years (range: 4.3–7.1 years)” (opens the source at this quote in a new tab)
“Patient 5 had LV systolic dysfunction (LVEF <40%) at enrollment and had progressive heart failure requiring transplantation 5m following RP-A501 treatment and is not evaluable for efficacy.” (opens the source at this quote in a new tab)
“Patient underwent heart transplant at 4.8 years post-RP-A501 infusion; post data cut.” (opens the source at this quote in a new tab)

Sponsor safety conclusion in the publication abstract

“A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a period of 24 to 54 months.” (opens the source at this quote in a new tab)

Adverse event counts by preferred term for all seven participants

No evidence found.

Vector shedding

No evidence found.

Summary

RP-A501-0219 was a non-randomized, open-label phase 1 trial with no control group. It treated 7 male participants (5 aged 15 years or older and 2 aged 11 to 14 years) at 2 of its 3 registered sites in the United States. Two dose levels were given, 6.7 × 10¹³ GC/kg to 5 participants and 1.1 × 10¹⁴ GC/kg to 2 participants, and the higher dose was discontinued in 2021 in agreement with the FDA after a grade 4 thrombotic microangiopathy event in 1 of the 2 participants who received it. Immunomodulation differed between participants: the October 2026 presentation lists steroid alone in 1 participant, steroid plus tacrolimus in 2, rituximab plus steroid plus tacrolimus in 2, and rituximab plus steroid plus sirolimus in 2, and adherence was confirmed in 6 of 7 participants. Eligibility changed during the trial: exclusion of ejection fraction below 40% was implemented before the pediatric cohort was enrolled, and an FDA clinical hold ran from May 2021 to August 16, 2021. The registered primary outcomes were treatment-related adverse events, histologic correction on endomyocardial biopsy, and clinical stabilization at 3 years. The reported efficacy measures (LAMP2 protein expression, left ventricular mass index, wall thickness, troponin I, natriuretic peptides, NYHA class, and KCCQ-12) are biomarker, imaging, and functional measures in 6 of the 7 participants (86%); the participant with ejection fraction below 40% at enrollment underwent heart transplantation 5 months after infusion and is described as “not evaluable for efficacy”. No sample size justification, statistical analysis plan, or hypothesis test was found in the public documents, and no results are posted on the registry record.

In the July 31, 2026 data extraction the most recent visit differed by participant (36 to 84 months), left ventricular mass index came from magnetic resonance imaging in some participants and from echocardiography in others, and troponin I values came from “high-sensitivity and earlier tests”. At the most recent visit, left ventricular mass index had decreased by 10% or more in 4 of 6 participants (67%), by 7% in 1, and had increased by 3% in 1, in whom posterior wall thickness had increased by 66%. One participant had grade 0 LAMP2 staining at the 30-month and 36-month biopsies, and 1 pediatric participant underwent heart transplantation 4.8 years after infusion, after the data extraction. The comparison with natural history used “Unpublished data from International Danon Disease Registry” (20 patients for BNP with r² of 0.246, and 22 patients for left ventricular mass with r² of 0.846), and in the natural history comparison presented in May 2023, 3 of the 8 natural history patients later entered the trial. Sources differ on some values: the baseline ejection fraction of the transplanted participant is given as 35% and as 32%, a 2022 congress abstract reports 1 participant in NYHA class III at baseline while the participant-level tables list class II for all 7, and the 57% median natriuretic peptide reduction is attributed to NT-proBNP in one company document and to BNP in another. The trial was funded by Rocket Pharmaceuticals, and 8 of the 13 authors of the publication list a Rocket Pharmaceuticals affiliation. The pivotal cohort of the phase 2 trial uses 3.8 × 10¹³ GC/kg with rituximab, steroid, and sirolimus, a dose that no phase 1 participant received, and the sponsor states that “results from earlier cohorts may not predict outcomes at the recalibrated dose under the modified protocol”.

Registered study goal

“The goal of this international observational study is to learn about the natural history of Danon disease in male patients (≥8 years of age) and female patients (8 to 50 years of age).” (opens the source at this quote in a new tab)
“The study is designed to describe the natural history of Danon disease, a rare X-linked genetic disorder, and one of the most severe and penetrant forms of inherited cardiomyopathy.” (opens the source at this quote in a new tab)

Data to be collected on the clinical course under standard care

“This study will collect data about the clinical course of Danon disease, including signs and symptoms, key clinical events, and the impact of the disease on quality of life as managed with the current standard of care.” (opens the source at this quote in a new tab)

External control arm for RP-A501 trial participants

“A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.” (opens the source at this quote in a new tab)

“The cohort of patients in the study will provide data about Danon disease managed with available standard of care and thus, serve as an external comparator arm for the Phase 2 trial and provide important context to assess the efficacy of RP-A501 in patients enrolled in the Phase 2 trial.” (opens the source at this quote in a new tab)

Stated need for prospective collection at pre-specified intervals

“Given the rarity of the condition, most prior efforts characterizing disease progression have utilized retrospective records that include variable diagnostics/testing intervals.” (opens the source at this quote in a new tab)
“To describe the Natural History (NH) of DD in a comprehensive/unbiased way, there is a need to standardize a protocol for prospectively collecting cardiac testing at pre-specified intervals, while taking advantage of retrospectively collected patient data.” (opens the source at this quote in a new tab)

Study identifiers, dates, and status

Item	Registry record
Sponsor protocol number	“RP-NI-A501-0223”
Other sponsor identifier	“LAMPLIGHT-NH”
Sponsor	“Rocket Pharmaceuticals Inc.”
Recruitment status	“Recruiting”
Study start (actual)	“2023-12-20”
Primary completion (estimated)	“2029-12”
Study completion (estimated)	“2030-03”
First posted	“2024-01-19”
Last update posted	“2026-07-28”

Number of registered locations

“This study has 15 locations” (opens the source at this quote in a new tab)

Registered sites by country

Country	Site
United States	“Phoenix Children's Hospital”
United States	“University of California, San Diego”
United States	“Children's Hospital Colorado”
United States	“University of Florida College of Medicine”
United States	“University of Michigan”
United States	“Washington University”
United States	“Columbia University Medical Center/New York Presbyterian”
United States	“University of Texas, Southwestern”
United States	“Texas Children's Hospital”
Germany	“German Heart Center Munich”
Israel	“Sheba Medical Center”
Italy	“Azienda Ospedaliera Universitaria Meyer IRCCS”
Spain	“Sant Joan de Déu Hospital”
Spain	“Hospital Universitario Puerta de Hierro Majadahonda”
United Kingdom	“University College London - Great Ormond Street Institute of Child Health”

United Kingdom ethics review and study duration

Item	Research summary
Integrated Research Application System identifier	“339721”
Sponsor organisation	“Rocket Pharmaceuticals, Inc.”
Duration of study in the United Kingdom	“2 years, 4 months, 17 days”
Research ethics committee	“South Central - Berkshire Research Ethics Committee”
Research ethics committee reference	“24/SC/0094”
Date of opinion	“6 Jun 2024”
Opinion	“Further Information Favourable Opinion”

Official title and hybrid data collection

“An Observational Study of Genetic Cardiomyopathy, Danon Disease” (opens the source at this quote in a new tab)
“This is an international observational study with both retrospective and prospective data collection.” (opens the source at this quote in a new tab)
“A hybrid (retrospective and prospective data collection) approach is being used to generate robust and longitudinal data.” (opens the source at this quote in a new tab)

“The current study is a multi-country, observational, non-interventional, longitudinal study with prospective and retrospective data collection that aims to describe the natural course of Danon disease progression.” (opens the source at this quote in a new tab)

Registered design details

Design element	Registry record
Study type	“Observational”
Observational model	“Cohort”
Time perspective	“Prospective”
Sampling method	“Non-Probability Sample”
Group 1	“Prospective Cohort”
Group 2	“Retrospective Cohort”
Intervention	“Other: No intervention”

Visit schedule and duration of prospective follow-up

“Yearly lab and echocardiogram (ECHO) and electrocardiogram (EKG) assessments, reporting on key events, and the impact of the disease on quality of life, as it is managed with current treatments, for a total of 3 years.” (opens the source at this quote in a new tab)
“Visits take place at a study site or, in some cases, can be conducted remotely.” (opens the source at this quote in a new tab)

Regulatory basis for a natural history comparator: December 2022 statement

“we anticipate utilizing a single arm open-label trial design with a robust natural history comparator, pursuant to the FDA’s acknowledgment of the challenges associated with executing a randomized controlled trial in Danon Disease” (opens the source at this quote in a new tab)
“We look forward to continued dialogue with the FDA on the design for our proposed pivotal trial, including discussion of appropriate external controls for the study and appropriate endpoints to support accelerated approval.” (opens the source at this quote in a new tab)

Natural history comparator in the pivotal trial design aligned with the FDA: September 2023 statements

“Final alignment reached on a single arm, open-label study with natural history comparator and a biomarker based co-primary endpoint consisting of LAMP2 protein expression and Left Ventricular (LV) Mass” (opens the source at this quote in a new tab)
“A global natural history study will serve as an external comparator and run concurrently to the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

“NHS to serve as external comparator” (opens the source at this quote in a new tab)
“Pivotal, global, single-arm, open label study with external comparator” (opens the source at this quote in a new tab)

Natural history data sets named as the external comparator in September 2023

“Prospective, Retrospective Natural History Study as External Comparator” (opens the source at this quote in a new tab)
“Allows for robust comparisons and aligned with FDA guidance” (opens the source at this quote in a new tab)

Data set	Males	Females	Status
“Prospective Natural History Study”	“9 Males”	“1 Female”	“Initiated in 2019, study complete”
“US Retrospective Natural History”	“51 Males”	“67 Females”	“Initiated in 2006”
“EU Retrospective Natural History Study”	“21 Males”	“38 Females”	“Enrollment complete; analysis in Q4 2023”

Planned sponsor-initiated prospective study and its design elements: September 2023

“To be expanded through an additional prospective Rocket-initiated natural history study” (opens the source at this quote in a new tab)
“Entry criteria and endpoints similar to Phase 2 trial” (opens the source at this quote in a new tab)
“Appropriate matching to ensure robust comparisons” (opens the source at this quote in a new tab)
“Retrospective data collection to supplement prospective evaluation to ensure sufficient comparative data” (opens the source at this quote in a new tab)

Use of the external comparator arm at each time point: September 2023

“Each patient’s baseline AND matched external comparator arm together provide robust control data to assess treatment effect” (opens the source at this quote in a new tab)
“External comparator arm serves as control at each timepoint” (opens the source at this quote in a new tab)
“Note: Illustrative representation of potential treatment effects versus natural history” (opens the source at this quote in a new tab)

External comparator role: Form 10-K filed February 2026

“A global natural history study is also running concurrently to the Phase 2 pivotal trial and will serve as an external comparator.” (opens the source at this quote in a new tab)

Description of the natural history study: Form 10-Q filed August 2026

“A global natural history study is also running concurrently with the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

Referral of male participants from the natural history study to the gene therapy study

“If a male patient joins the Natural History study and is interested in learning more about participation in the Gene Therapy study, a discussion should be had with the Natural History study Principal Investigator to receive a referral to the Gene Therapy study team.” (opens the source at this quote in a new tab)

Study population

“Male patients 8 years of age and over, Female patients 8 to 50 years of age (at the point of enrollment) with confirmed Danon disease recruited from a range of applicable care settings.” (opens the source at this quote in a new tab)

Registered age and sex limits

Item	Registry record
Ages eligible for study	“8 Years and older”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

Inclusion criteria: prospective cohort

Criterion	Quoted registry text
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory”
Consent	“Patient or parent/legal guardian are capable and willing to provide signed informed consent”
Age	“Age ≥ 8 years at enrollment”
Additional criterion for females	“Evidence of left ventricular hypertrophy in the 12 months prior to or at enrollment.”

Inclusion criteria: retrospective-only cohort

Criterion	Quoted registry text
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory”
Consent	“Patient or parent/legal guardian are capable and willing to provide signed informed consent, as required by local regulations”
Age	“Age ≥ 8 years at enrollment”
Prior advanced heart failure therapy	“Prior cardiac transplantation or prior mechanical circulatory support”
Available records	“At least 30 days of retrospective medical records available prior to cardiac transplantation or mechanical circulatory support”
Additional criterion for females	“Prior evidence of left ventricular hypertrophy.”

Exclusion criteria

Cohort	Quoted registry text
All cohorts	“Concurrent enrollment in any other clinical investigation involving use of an investigational agent for any condition at time of enrollment to this study that could confound interpretation of this study”
All cohorts	“Previous treatment with a gene therapy”
Prospective cohort	“Prior mechanical circulatory support at time of enrollment to this study”
Prospective cohort	“Prior cardiac transplantation at time of enrollment to this study”
Prospective cohort	“Female patients: Age >51 years at enrollment”

Eligibility as described on the recruitment website

“Males, age 8 years or older” (opens the source at this quote in a new tab)
“Females, age 8 to 50 years” (opens the source at this quote in a new tab)
“Diagnosed with Danon disease” (opens the source at this quote in a new tab)

Key eligibility criteria of the pivotal trial that the external control arm supports

Criterion	Quoted registry text
Sexes eligible for study	“Male”
Age	“Age ≥8 years.”
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.”
Systolic function	“Left ventricular ejection fraction (LVEF) ≥ 50%.”
Functional class	“New York Heart Association (NYHA) Class II to III.”
Troponin	“High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (ULN) ≤ 12 months prior to screening.”
Excluded: prior transplantation	“Prior cardiac or other organ (lung, liver, other) transplantation.”

No study intervention

“Other: No intervention” (opens the source at this quote in a new tab)

“You do not receive any new therapy as part of the study.” (opens the source at this quote in a new tab)

Continuation of standard care during the study

“People in the study stay on the treatments they already use and will continue to see their doctor for regular care.” (opens the source at this quote in a new tab)

“as managed with the current standard of care” (opens the source at this quote in a new tab)

Primary outcome definition

Outcome measure	Measure description	Time frame
“Left Ventricular Mass Index (LVMI) by echocardiogram”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”

Secondary outcomes: biomarkers, symptoms, quality of life, and clinical events

Outcome measure	Measure description	Time frame
“Cardiac biomarkers (hsTnI)”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36 (when available)”
“Cardiac biomarkers (NT-proBNP, BNP)”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36 (when available)”
“NYHA class”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“KCCQ-12”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“PedsQL”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization”	“Evaluation over duration of follow up”	“Month 12, 24, 36”
“Six Minute Walk Test”	“This test measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes.”	“Month 12, 24, 36”

Secondary outcomes: electrocardiogram, anti-AAV9 antibody titer, and laboratory tests at enrollment

Outcome measure	Measure description	Time frame
“ECG”	“Twelve-lead ECGs are relevant to describe changes in cardiac rhythm that may further contextualize the clinical events/endpoints”	“Month 12, 24, 36”
“Anti-AAV9 titer”	“Change in antibody assay findings over time”	“Month 12, 24, 36”
“CBC”	“CBC with differential”	“At enrollment”
“Serum Chemistry”	“Electrolytes”	“At enrollment”
“Serum chemistry”	“Creatinine”	“At enrollment”
“Serum chemistry”	“LDH”	“At enrollment”
“Serum chemistry”	“BUN”	“At enrollment”
“Serum chemistry”	“eGFR”	“At enrollment”
“Serum chemistry”	“LFT”	“At enrollment”

Primary endpoint of the pivotal trial that the external control arm supports

“Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC), AND, ≥ 10% decrease in LVMI from baseline.” (opens the source at this quote in a new tab)
“12 months post-infusion” (opens the source at this quote in a new tab)

Alignment of natural history endpoints with the pivotal trial: September 2023 statement

“Entry criteria and endpoints similar to Phase 2 trial” (opens the source at this quote in a new tab)

Company rationale for left ventricular mass as a measure of disease progression: September 2023

“Left ventricular hypertrophy is the most consistent phenotypic feature of disease progression” (opens the source at this quote in a new tab)
“Retrospective natural history shows year-over-year increases in LV mass in Danon disease patients” (opens the source at this quote in a new tab)
“Data from the Natural History Studies demonstrated increases in key echo parameters in DD that are known to predict disease progression in other types of cardiomyopathy” (opens the source at this quote in a new tab)

Interpretation of the pivotal trial primary endpoint in the context of the concurrent natural history study

“Primary endpoint will be assessed in the context of biomarkers, symptoms, QOL, clinical events derived from secondary endpoints and concurrent natural history study” (opens the source at this quote in a new tab)

Planned enrollment: registry record

Enrollment type	Participants
Estimated	“60”

Enrollment as of August 2026

“In parallel with the pivotal Phase 2 trial, Rocket’s global natural history study has enrolled more than 50 patients, including both males and females, building an increasingly robust longitudinal dataset to further characterize Danon disease.” (opens the source at this quote in a new tab)

Number of participants in the external control arm subset

No evidence found.

Analyzed population

No evidence found.

Registered cohorts

“Prospective Cohort” (opens the source at this quote in a new tab)
“Retrospective Cohort” (opens the source at this quote in a new tab)

Subset used as the external control arm

“A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.” (opens the source at this quote in a new tab)

Matching of the external comparator arm: September 2023 statements

“Appropriate matching to ensure robust comparisons” (opens the source at this quote in a new tab)
“Each patient’s baseline AND matched external comparator arm together provide robust control data to assess treatment effect” (opens the source at this quote in a new tab)

Matching variables and selection rules for the external control arm

No evidence found.

Statistical method for comparison with the pivotal trial

No evidence found.

Study results

No evidence found.

Source of the natural history comparison shown in the October 2026 company presentation

“Differs significantly from expanded natural history data” (opens the source at this quote in a new tab)
“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)

Summary

RP-NI-A501-0223 is an observational cohort study with no study intervention, sponsored by Rocket Pharmaceuticals, the developer of RP-A501. No results are posted on the registry record and no results publication was identified; the one peer-reviewed document is a design abstract. The record estimates enrollment of 60 participants at 15 sites in 6 countries, the company reported more than 50 participants enrolled in August 2026, and the estimated primary completion date is December 2029, which is later than the June 2028 estimated primary completion of the pivotal trial. A subset of participants serves as the external control arm for a single-arm, open-label trial. The size of that subset, the rules for selecting it, the matching variables, and the statistical method of comparison have not been published; the September 2023 company presentation refers to “Appropriate matching” without naming variables. Eligibility differs between the two studies: the natural history study enrolls males aged 8 years and older and females aged 8 to 50 years, and its retrospective-only cohort requires prior cardiac transplantation or mechanical circulatory support, whereas the pivotal trial enrolls males aged 8 years and older with a left ventricular ejection fraction of at least 50%, New York Heart Association class II to III, and elevated high-sensitivity troponin I, and excludes prior transplantation. The primary outcome is left ventricular mass index by echocardiogram at months 12, 24, and 36, and part of the data is collected retrospectively from medical records; the design abstract states that retrospective records “include variable diagnostics/testing intervals”. The registered outcomes do not include myocardial LAMP2 protein expression, which is one of the two components of the pivotal trial's primary endpoint. The recruitment website states that a male participant may be referred from the natural history study to the gene therapy study. The Form 10-K filed in February 2026 states that the study “will serve as an external comparator”, and the Form 10-Q filed in August 2026 describes it as “running concurrently with the Phase 2 pivotal trial”. The natural history comparison shown in the October 2026 company presentation is attributed to “Unpublished data from International Danon Disease Registry”.

Overarching goal

“The overarching goal of this retrospective, multicenter, international study is to gain a better understanding of the Natural History of Danon disease, by collecting de-identified information from patients with this condition treated.” (opens the source at this quote in a new tab)
“This retrospective, multicenter, international, longitudinal, non- interventional study of DD patients with confirmed LAMP2 mutation aims at characterizing the Natural History of disease in males and females.” (opens the source at this quote in a new tab)

Primary objective

“Primary objective: Determine how specific cardiac manifestations in patients diagnosed with Danon disease change over time.” (opens the source at this quote in a new tab)
“Essential echocardiography and/or MRI-based parameters include: thickness of the Left Ventricular Posterior Wall at end-diastole (LVPWd); thickness of the Interventricular Septum at end-diastole (IVSd); Left Ventricular mass (LVmass); Left Ventricular Ejection Fraction (LVEF).” (opens the source at this quote in a new tab)

Secondary objectives

“Secondary objectives: Describe the progression of other cardiac and extracardiac manifestations in patients diagnosed with Danon disease, including, but not limited to: serologic markers of heart failure, serologic markers of muscle injury, risk and frequency of arrhythmias, comprehensive echocardiogram and MRI-based assessments of cardiomyopathy, overall survival, and event-free survival (as defined subsequently).” (opens the source at this quote in a new tab)

Exploratory objectives

“Exploratory objectives: Describe the diagnostic pathway of Danon disease, therapeutic management and local centers' approaches to genetic testing for LAMP2 mutations.” (opens the source at this quote in a new tab)
“Identify key Natural History trends to inform a prospective European Union (EU) natural history study and plan for a potential gene therapy trial for DD patients in the EU.” (opens the source at this quote in a new tab)

Support for the design of the RP-A501 pivotal trial

“The Real-world data collected from patients in this natural history study will help support the overall development and protocol design of the RP-A501 gene therapy pivotal trial to be submitted to the health authorities.” (opens the source at this quote in a new tab)

Identification of treating centers and planning of later studies

“Additionally, this study will allow identification of the core centers managing DD patients in several countries as well as the description of the disease characteristics, diagnosis pathway and disease progression.” (opens the source at this quote in a new tab)
“This will inform the development of patient profiles for future studies, including a potential prospective observational study to investigate the burden of disease among DD patients and an international patient registry for Danon disease.” (opens the source at this quote in a new tab)

Study identifiers, dates, and status

Item	Registry record
Sponsor protocol number	“RP-NI-A501-0122”
Sponsor	“Rocket Pharmaceuticals Inc.”
Recruitment status	“Completed”
Study start (actual)	“2022-09-26”
Primary completion (actual)	“2023-10-31”
Study completion (actual)	“2023-10-31”
First posted	“2022-09-22”
Last update posted	“2023-11-21”

Number of registered locations

“This study has 15 locations” (opens the source at this quote in a new tab)

Registered sites by country

Country	Site
Czechia	“Institut klinické a experimentální medicíny (IKEM)- Institute for Clinical and Experimental Medicine”
France	“CHU de Nantes, Hôpital Laennec”
France	“APHP, Hôpital de la Pitié Salppêtrière - Charles Foix”
France	“CHU de Rennes, Hôpital Pontchaïllou”
Ireland	“Mater Misericordiae University Hospital”
Italy	“Ospedale Papa Giovanni XXIII di Bergamo ASST Pap Giovanni XXIII Hospital”
Italy	“University of Florence Dept. of Experimental and Clinical Medicine”
Italy	“IRCCS Burlo Garogolo- Hospital Burlo Garofolo”
Spain	“Hospital Clínic de Barcelona - Barnaclínic+”
Spain	“Hospital Universitario de Bellvitge- Bellvitge University Hospital”
Spain	“Hospital Universitario La Paz - La Paz University Hospital”
Spain	“Hospital Universitario Puerta de Hierro Majadahonda Puerta de Hierro Majadahonda - University Hospital”
Spain	“Hospital Universitario Virgen de la Victoria- Virgen de la Victoria University Hosptial”
Spain	“Hospital Álvaro Cunqueiro”
Spain	“Hospital Universitario y Politécnico La Fe, Instituto De Investigación Sanitaria La Fe, La Fe University and Polytechnic Hospital”

Official title and registered design

“A Retrospective, Multicenter, International Study to Characterize the Natural History of Danon Disease” (opens the source at this quote in a new tab)
“This is a multicenter, international, non-interventional, natural history study designed to collect longitudinal retrospective clinical information on patients with Danon disease (DD).” (opens the source at this quote in a new tab)

Two study parts: feasibility assessment and retrospective chart review

“This study is composed of 2 parts:” (opens the source at this quote in a new tab)
“Feasibility study: to identify participating sites, assess site and team capabilities, confirm the site and investigator qualification for taking part in the study,” (opens the source at this quote in a new tab)
“Retrospective chart review: Data will be collected retrospectively by means of a chart review of living and/or deceased DD patients with a confirmed lysosome associated membrane protein-2 gene (LAMP2) mutation” (opens the source at this quote in a new tab)

Registered design details

Design element	Registry record
Study type	“Observational”
Observational model	“Cohort”
Time perspective	“Retrospective”
Sampling method	“Probability Sample”
Group 1	“Heart Transplant or Cardiac Assist Device”
Group 2	“No Intervention”
Plan to share individual participant data	“No”

Listing as a European retrospective data set within the external comparator: September 2023 company presentation

“EU Retrospective Natural History Study” (opens the source at this quote in a new tab)
“Prospective, Retrospective Natural History Study as External Comparator” (opens the source at this quote in a new tab)

Study population

“Female and male patients with confirmed diagnosis of Danon disease based on a genetic test positive for a mutation in LAMP2” (opens the source at this quote in a new tab)

Registered age and sex limits

Item	Registry record
Ages eligible for study	“6 Years and older”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

Inclusion criteria

Criterion	Quoted registry text
Age and sex	“Patients older than 6 years old and any sex.”
Genetic confirmation	“Patients with a confirmed genetic mutation in LAMP2.”
Living participants without heart transplantation or a cardiac assist device	“A minimum of 6 months of longitudinal data, including at least 2 echocardiograms or MRIs at least 6 months apart, prior to most recent follow-up visit or enrollment in Sponsor's gene therapy clinical trial.”
Deceased participants, or living participants with heart transplantation or a cardiac assist device	“At least 1 echocardiogram or MRI assessment prior to heart transplantation/ cardiac assist device placement or death”
Consent	“Informed consent/assent by the patient and/or their legally authorized representative (if the patient is living at the time of enrollment).”

Exclusion criterion

“Diagnosis of Danon disease without genetic testing confirmation.” (opens the source at this quote in a new tab)

Minimum follow-up data stated in the brief summary

“For living patients (who have not undergone heart transplantation or placement of a cardiac assist device), availability of at least 6-month cardiology follow-up data,” (opens the source at this quote in a new tab)
“For living patients who underwent heart transplantation or placement of a cardiac assist device, and for deceased patients, at least 1 MRI or echo assessment prior to heart transplantation/cardiac assist device placement or death.” (opens the source at this quote in a new tab)

No study intervention

“non-interventional” (opens the source at this quote in a new tab)

Standard-of-care procedures that define the registered groups

Registered item	Quoted registry text
“Procedure: Heart Transplant”	“Patients who have undergone a heart transplant as standard of care (SOC) procedure”
“Device: Cardiac Assistive Device”	“Patients who have undergone a placement of a cardiac assistive device”

Description of current treatment in the registry record

“There is currently no therapy available to cure, or even prevent disease progression.” (opens the source at this quote in a new tab)
“DD treatment is thus primarily supportive therapy, and survival beyond 25 years without a cardiac transplantation is improbable for afflicted male patients.” (opens the source at this quote in a new tab)

Primary outcome definitions

Outcome measure	Parameter as described	Time frame
“Cardiac Manifestations- LVPWd”	“thickness of the left ventricular posterior wall end diastole and end systole (LVPWd)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations- lVSd”	“thickness of the left ventricular systolic dysfunction (IVSd)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations- LVmass”	“left ventricular mass (LVmass)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations - LVEF”	“left ventricular ejection fraction (LVEF)”	“Retrospective minimum of 6 months”

Analysis common to the four primary outcomes

“Descriptive analysis will be conducted to characterize specific cardiac manifestations in patients diagnosed with Danon disease, and changes over time.” (opens the source at this quote in a new tab)
“Data collected will be analyzed by 6-month intervals and by the changes from initial evaluation over each 6-month interval.” (opens the source at this quote in a new tab)

Parameter definitions in the detailed description

“Essential echocardiography and/or MRI-based parameters include: thickness of the Left Ventricular Posterior Wall at end-diastole (LVPWd); thickness of the Interventricular Septum at end-diastole (IVSd); Left Ventricular mass (LVmass); Left Ventricular Ejection Fraction (LVEF).” (opens the source at this quote in a new tab)

Stated relation between cardiac disease severity and prognosis

“Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias.” (opens the source at this quote in a new tab)
“The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death.” (opens the source at this quote in a new tab)

Secondary outcomes: serologic markers

Outcome measure	Marker as described	Time frame
“Serologic Markers & Imaging - BNP”	“serologic markers of heart failure which include B-type natriuretic peptide (BNP)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging Pro-BNP”	“serologic markers of heart failure which include Pro- B-type natriuretic peptide (Pro-BNP)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- CK-MB”	“serologic markers of heart failure which include creatine kinase - MB (CK-MB)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- Troponin”	“serologic markers of heart failure which include Troponin”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- CPK”	“serologic markers of muscle injury, which include creatine phosphokinase (CPK)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- transaminases”	“serologic markers of muscle injury, which include transaminases”	“Retrospective minimum of 6 months”

Secondary outcomes: echocardiogram and magnetic resonance imaging assessments

Outcome measure	Assessment as described	Time frame
“Serologic Markers & Imaging- Echo/MRI”	“measures of cardiac hypertrophy or dilation”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- BP”	“measures of systolic and diastolic function”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- GLS”	“measures of Global Longitudinal Strain (GLS)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- E/A”	“measures of mitral inflow ratio of the early (E) to late (A) (ventricular filling velocities (E/A))”	“Retrospective minimum of 6 months”

Descriptive statistics planned for serologic and imaging outcomes

“Mean values, standard deviations, medians and changes in means will be provided” (opens the source at this quote in a new tab)

Secondary outcomes: arrhythmia, device placement, and survival

Outcome measure	Measure description	Time frame
“Arrhythmias”	“Time to event (risk of arrhythmia), for each of the following: supraventricular arrhythmias and non-sustained ventricular arrhythmias on Holter or similar monitoring, treatment with anti-arrhythmic medications”	“Retrospective minimum of 6 months”
“Wolf-Parkinson-White syndrome”	“Time to event of Wolf-Parkinson-White syndrome (WPW) on electrocardiogram”	“Retrospective minimum of 6 months”
“ICD Placement”	“Time to event of Implantable cardioverter-defibrillators (ICD) placement”	“Retrospective minimum of 6 months”
“Reason for ICD Placement”	“Reasoning for ICD placement will be summarized by frequency of the reasons”	“Retrospective minimum of 6 months”
“Overall Survival”	“Overall survival will be analyzed using Kaplan-Meier estimates.”	“Retrospective minimum of 6 months”
“Event-free survival”	“Event-free survival (EFS) will be analyzed using Kaplan-Meier estimates.”	“Retrospective minimum of 6 months”

Event-free survival by event tier

“EFS will be provided for Tier 1 events, Tier 1 + Tier 2 events, and Tier 1 + Tier 2 +Tier 3 events.” (opens the source at this quote in a new tab)

Definition of the event tiers

No evidence found.

Planned enrollment

No evidence found.

Actual enrollment: registry record

Enrollment type	Participants
Actual	“59”

Enrollment status of the European retrospective study in September 2023

“Enrollment complete; analysis in Q4 2023” (opens the source at this quote in a new tab)

Analyzed population

No evidence found.

Registered groups

Group	Quoted registry text
“Heart Transplant or Cardiac Assist Device”	“For living patients who underwent heart transplantation or placement of a cardiac assist device, and for deceased patients, at least 1 MRI or echo assessment prior to heart transplantation/cardiac assist device placement or death.”
“No Intervention”	“for living patients (who have not undergone heart transplantation or placement of a cardiac assist device), availability of at least 6-month cardiology follow-up data”

Analysis intervals

“Data collected will be analyzed by 6-month intervals and by the changes from initial evaluation over each 6-month interval.” (opens the source at this quote in a new tab)

Censoring in survival analyses

“Patients lost to follow-up or who complete the study will be censored at the last follow-up time.” (opens the source at this quote in a new tab)

Sex of participants in the European retrospective study: September 2023 company presentation

Data set	Males	Females
“EU Retrospective Natural History Study”	“21 Males”	“38 Females”

Other baseline characteristics

No evidence found.

Study results

No evidence found.

Planned timing of the analysis as stated in September 2023

“Enrollment complete; analysis in Q4 2023” (opens the source at this quote in a new tab)

Source of the natural history figures in the September 2023 company presentation

“Reflects estimated LV Mass increase over 12-18M for DD patients based on retrospective natural history data-set (shown on slide 20).” (opens the source at this quote in a new tab)
“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)

Source of the natural history comparison in the October 2026 company presentation

“Differs significantly from expanded natural history data” (opens the source at this quote in a new tab)
“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)

Summary

RP-NI-A501-0122 is a retrospective chart review with no study intervention, sponsored by Rocket Pharmaceuticals, the developer of RP-A501. The registry record reports 59 participants enrolled at 15 sites in 5 European countries and completion on 2023-10-31. No results are posted on the record and no results publication was identified; the September 2023 company presentation lists an “EU Retrospective Natural History Study” of 21 male and 38 female participants (59 in total) with “analysis in Q4 2023”. Data were collected by chart review from echocardiograms or magnetic resonance imaging already performed, and the record sets no imaging method or schedule; a living participant without heart transplantation or a cardiac assist device needed at least 2 imaging assessments at least 6 months apart, and a deceased participant or a participant with transplantation or a device needed at least 1 assessment. The study enrolled participants of either sex older than 6 years, including deceased participants and participants with heart transplantation or a cardiac assist device, whereas the pivotal trial of RP-A501 enrolls males aged 8 years and older with a left ventricular ejection fraction of at least 50% and excludes prior transplantation. The primary outcomes are left ventricular posterior wall thickness, interventricular septal thickness, left ventricular mass, and ejection fraction; the record does not list left ventricular mass index, the measure used in the pivotal trial's primary endpoint. The outcome descriptions for posterior wall and septal thickness on the record differ from the definitions in its detailed description, and the event tiers used for event-free survival are not defined. The record states that the data support the protocol design of the pivotal trial, and the September 2023 presentation lists the study among three natural history data sets under the heading “Prospective, Retrospective Natural History Study as External Comparator”; how its participants enter the comparison has not been published. The natural history figures in the September 2023 and October 2026 company presentations are attributed to “Unpublished data from International Danon Disease Registry”.