RP-A501 (AAV9.LAMP2B)

RP-A501 is investigational and has no established place in therapy. The pivotal phase 2 trial enrolls males aged 8 years or older with a pathogenic or likely pathogenic LAMP2 variant, left ventricular hypertrophy with an ejection fraction of 50% or more, New York Heart Association class II to III symptoms, and elevated high-sensitivity troponin I. It excludes anti-AAV9 neutralizing antibody titers above 1:40, severe heart failure requiring advanced therapies, and prior transplantation. The studied population therefore has disease earlier than the end stage at which heart transplantation is used. Reduced ejection fraction was excluded after the 1 phase 1 participant with baseline systolic dysfunction progressed to transplantation 5 months after infusion. The company states that its initial focus is males with symptomatic hypertrophic cardiomyopathy and presents females and males before cardiomyopathy onset as potential later expansions that would need additional clinical evidence and regulatory approval.

The trial care setting is a specialized center. The registry lists 6 recruiting locations in 4 countries, participants are hospitalized for infusion and safety monitoring, the first 3 participants treated at the recalibrated dose were discharged 1 to 2 weeks after infusion, and site follow-up continues for 5 years. Treatment involves endomyocardial biopsy, which supplies one of the two co-primary endpoint criteria, and an immunomodulatory regimen of rituximab, sirolimus, and corticosteroids that the company states is discontinued 2 to 3 months after infusion. Before a launch that the company projects for mid-2029, its stated plans include genetic testing of young people with hypertrophic cardiomyopathy, cascade testing of relatives, and relationships with treatment centers; it reports more than 900 identified patients in the United States and a diagnosis rate under 10%. In a survey of 123 cardiology providers, 85% had never referred a patient to a gene therapy trial and 51% recognized the need for immunosuppression expertise.