Pediatric participants: age limits of each interventional trial

“Age ≥15 years for cohorts 1 and 2; 8-14 years for cohorts 1A.” (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)

“Age ≥8 years.” (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 4: Males age ≥ 8 years [N=12 subjects; enrolling]” (opens the source at this quote in a new tab)

Pediatric participants: ages of those dosed in phase 1

“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)

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

Pediatric participants: dosing and immunomodulation in the phase 1 pediatric cohort

“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)
“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)

Pediatric participants: sequential safety run-in in the phase 2 trial

“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)

Pediatric participants: European paediatric investigation plan waiver for children under 3 years

“the paediatric population from birth to less than 3 years;” (opens the source at this quote in a new tab)
“on the grounds that clinical studies with the specific medicinal product cannot be expected to be of significant therapeutic benefit to or fulfil a therapeutic need of the specified paediatric subset(s).” (opens the source at this quote in a new tab)

Pediatric participants: studies and age groups in the European paediatric investigation plan

“From 3 years to less than 18 years of age.” (opens the source at this quote in a new tab)
“Open-label, non-randomised, single dose trial to evaluate safety and efficacy of RP-A501 in male patients from 8 years to less than 18 years of age (and adults) with Danon disease with any confirmed lysosome-associated membrane protein 2 (LAMP2) mutation(s) and cardiac involvement.” (opens the source at this quote in a new tab)
“Open-label, single-arm, single dose trial to evaluate safety and efficacy of RP-A501 in male patients from 3 to less than 8 years of age with Danon disease with a pathogenic or likely pathogenic LAMP2 mutation(s) and evidence of left ventricular hypertrophy with preserved systolic function.” (opens the source at this quote in a new tab)
“Studies 1, 2 and 5 are part of an extrapolation plan covering the paediatric population from 3 years to less than 8 years of age, as agreed by the PDCO.” (opens the source at this quote in a new tab)

Pediatric participants: deferral and completion date of the European paediatric investigation plan

“Date of completion of the paediatric investigation plan: By December 2034” (opens the source at this quote in a new tab)
“Deferral for one or more measures contained in the paediatric investigation plan: Yes” (opens the source at this quote in a new tab)

Children younger than 8 years: clinical data with RP-A501

No evidence found.

Pediatric participants: sirolimus labeling for children younger than 13 years

“The safety and efficacy of Rapamune in pediatric patients < 13 years have not been established.” (opens the source at this quote in a new tab)

Adults older than 21 years at infusion

No evidence found.

Females: excluded from the interventional trials

“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 will enroll adult and pediatric males with a confirmed diagnosis of DD.” (opens the source at this quote in a new tab)
“Male gender.” (opens the source at this quote in a new tab)

Females: included in the natural history study

“The goal of this international observational study is to learn about the natural history of Danon disease in male patients (≥8 years of age) and female patients (8 to 50 years of age).” (opens the source at this quote in a new tab)
“Female Prospective Cohort: Evidence of left ventricular hypertrophy in the 12 months prior to or at enrollment.” (opens the source at this quote in a new tab)
“Female patients: Age >51 years at enrollment” (opens the source at this quote in a new tab)

Females: planned study in the European paediatric investigation plan

“Open-label, single-arm, single dose trial to evaluate safety and efficacy of RP-A501 in female patients with Danon disease with a pathogenic or likely pathogenic LAMP2 mutation(s) and evidence of left ventricular hypertrophy with preserved systolic function.” (opens the source at this quote in a new tab)

Females: company statements on later indications, October 2026

“Rocket’s initial focus is males with symptomatic hypertrophic cardiomyopathy.” (opens the source at this quote in a new tab)

“Danon Females with earlier-onset HCM” (opens the source at this quote in a new tab)
“Danon Females with later-onset Cardiomyopathy” (opens the source at this quote in a new tab)
“Potential lifecycle expansions require additional clinical evidence and regulatory alignment and approval.” (opens the source at this quote in a new tab)
“Opportunities in additional patient populations would require further development and applicable regulatory approvals.” (opens the source at this quote in a new tab)

Females: commentary on extending eligibility

“A subset of female patients with Danon disease may present with a severe clinical course comparable to males, characterized by life-threatening arrhythmias and advanced heart failure” (opens the source at this quote in a new tab)
“Thus, eligibility to females could be potentially extended to patients with severe pediatric- or adolescent-onset disease.” (opens the source at this quote in a new tab)

Females: clinical data with RP-A501

No evidence found.

Males without hypertrophic cardiomyopathy: company statement on a later indication

“Danon Males pre-HCM” (opens the source at this quote in a new tab)
“Potential lifecycle expansions require additional clinical evidence and regulatory alignment and approval.” (opens the source at this quote in a new tab)

Reduced ejection fraction and advanced heart failure: exclusion criteria

“Left ventricular ejection fraction (LVEF) <40% at baseline.” (opens the source at this quote in a new tab)
“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)
“Presence or requirement of a Left Ventricular Assisted Device (LVAD).” (opens the source at this quote in a new tab)
“Requires mechanical ventilation.” (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)
“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)

Reduced ejection fraction: exclusion added to the phase 1 protocol after the first heart transplantation

“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)

“The only patient with baseline systolic dysfunction experienced progressive heart failure and ventricular arrhythmias requiring heart transplantation.” (opens the source at this quote in a new tab)
“The protocol was therefore refined excluding patients with reduced ejection fraction.” (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)

Reduced ejection fraction: outcome in the one participant enrolled with ejection fraction below 40%

“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 patient had worsening heart failure at baseline (LVEF <40%) attributed to Danon disease and required heart transplantation for cardiomyopathy progression five months after receiving RP-A501.” (opens the source at this quote in a new tab)

“Clinical parameters improved or remained stable (comparable to low dose cohort) in high dose patient treated before end-stage Danon disease (1006)” (opens the source at this quote in a new tab)

Anti-AAV9 seropositive individuals: exclusion threshold in both interventional trials

“Anti-AAV9 neutralizing antibody titer >1:40.” (opens the source at this quote in a new tab)

Anti-AAV9 seropositive individuals: pre-existing immunity in the participant with thrombotic microangiopathy

“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)

Anti-AAV9 seropositive individuals: labeling of an approved AAV9 product

“In ZOLGENSMA clinical trials, patients were required to have baseline anti-AAV9 antibody titers of ≤ 1:50, measured using an enzyme-linked immunosorbent assay (ELISA).” (opens the source at this quote in a new tab)
“The safety and efficacy of ZOLGENSMA in patients with anti-AAV9 antibody titers above 1:50 have not been evaluated.” (opens the source at this quote in a new tab)
“Following ZOLGENSMA infusion, increases from baseline in anti-AAV9 antibody titers occurred in all patients.” (opens the source at this quote in a new tab)

Individuals with a genetic predisposition to complement activation

“Regarding the TMA events, 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)

Higher body weight: total vector dose in the participant with thrombotic microangiopathy

“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)

Prior heart transplant recipients and recipients of other organ transplants: excluded from both interventional trials

“Prior cardiac or other organ (lung, liver, other) transplantation.” (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 heart transplant recipients: included in the retrospective cohort of the natural history study

“Prior cardiac transplantation or prior mechanical circulatory support” (opens the source at this quote in a new tab)
“At least 30 days of retrospective medical records available prior to cardiac transplantation or mechanical circulatory support” (opens the source at this quote in a new tab)

Renal impairment: phase 1 eligibility criterion

“Adequate renal function as defined by creatinine ≤ULN.” (opens the source at this quote in a new tab)

Renal impairment: clinical data with RP-A501

No evidence found.

Hepatic impairment: phase 1 eligibility criteria

“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)
“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).” (opens the source at this quote in a new tab)

Hepatic impairment: labeling of approved systemic AAV products

“ZOLGENSMA therapy should be carefully considered in patients with liver impairment.” (opens the source at this quote in a new tab)
“Cases of acute serious liver injury and acute liver failure have been reported with ZOLGENSMA in patients with preexisting liver abnormalities.” (opens the source at this quote in a new tab)

“The safety and efficacy of ELEVIDYS in patients with hepatic impairment or elevated GGT have not been studied.” (opens the source at this quote in a new tab)

Hematologic status: phase 1 eligibility criterion

“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)

History of thrombosis or thromboembolic events: exclusion criteria

“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)

Sirolimus hypersensitivity: phase 1 exclusion criterion

“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)

Pregnancy, lactation, and contraception requirements in the RP-A501 protocols

No evidence found.

Pregnancy and contraception: labeling of the immunomodulation agents and of an approved AAV9 product

“Effective contraception must be initiated before Rapamune therapy, during Rapamune therapy, and for 12 weeks after Rapamune therapy has been stopped.” (opens the source at this quote in a new tab)
“Azoospermia has been reported with the use of Rapamune and has been reversible upon discontinuation of Rapamune in most cases.” (opens the source at this quote in a new tab)

“Advise females of reproductive potential to use effective contraception during treatment with RITUXAN and for 12 months after the last dose.” (opens the source at this quote in a new tab)

“There are no available data regarding ZOLGENSMA use in pregnant women.” (opens the source at this quote in a new tab)