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.