Rocket Pharmaceuticals (RCKT) Study Update summary

Study background and design

• RP-A501 is an AAV9-based gene therapy targeting Danon disease, a rare X-linked disorder causing severe cardiomyopathy and neuromuscular deficits due to LAMP2 mutations.

• Phase I trial enrolled male patients aged 8+ with LAMP2 variants, cardiac hypertrophy, and heart failure symptoms; neutralizing antibodies to AAV9 were exclusionary.

• Three dosing cohorts: low-dose adults/adolescents, high-dose adults/adolescents, and low-dose pediatric patients.

• Immunomodulatory regimens included steroids and other agents to mitigate immune-related toxicities.

• The pivotal phase II trial is ongoing, using the low-dose regimen identified as optimal in phase I.

Safety and tolerability

• RP-A501 was generally well tolerated; most adverse events were mild or moderate and not related to therapy, with all serious adverse events reversible within 2-4 months post-dosing.

• Treatment-related SAEs included transient AST/ALT elevation, pyrexia, nausea/vomiting, and complement-mediated TMA in one high-dose patient.

• Steroid-induced skeletal myopathy and other immunomodulatory-related events resolved after discontinuation.

• No treatment-related SAEs were observed in the pediatric low-dose cohort.

• One patient with severe baseline heart failure required transplantation five months post-treatment.

Efficacy and biomarker outcomes

• All evaluable patients showed durable LAMP2 protein expression at 12 months and beyond, with one patient demonstrating robust expression at five years.

• Cardiac biomarkers (BNP, troponin) showed mean reductions of 57% and 84%, respectively, sustained up to 54 months.

• All patients improved from NYHA Class II to Class I, indicating resolution of heart failure symptoms, and improved KCCQ quality-of-life scores at 24-54 months.

• Imaging showed stable LVEF and sustained reductions in LV mass index (median 24% decrease), with all patients achieving ≥10% reduction at 12 months.

• All six evaluable patients were alive and transplant-free up to age 25 years.