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”.