RARE Daily

FDA Grants Regenerative Medicine Advanced Therapy Designation for Rocket’s Gene Therapy for Danon Disease

February 8, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has granted Regenerative Medicine Advanced Therapy designation to Rocket Pharmaceuticals’ RP-A501, an investigational adeno-associated virus-based gene therapy for the treatment of Danon disease, a devastating and fatal genetic cardiac disease for which there are no disease-altering therapies available.

Danon disease is a rare X-linked inherited disorder caused by mutations in the gene encoding lysosome-associated membrane protein 2 (LAMP-2), an important mediator of autophagy. This results in accumulation of autophagosomes and glycogen, particularly in cardiac muscle and other tissues, which ultimately leads to heart failure, and for male patients, frequent death during adolescence or early adulthood. It is estimated to have a prevalence of 15,000 to 30,000 patients in the U.S. and Europe. The only available treatment option for Danon Disease is cardiac transplantation, which is associated with substantial complications and is not considered curative. There are no specific therapies available for the treatment of Danon Disease.

The RMAT designation was granted based on positive safety and efficacy data from the phase 1 RP-A501 clinical trial and will provide the benefits of added intensive FDA guidance and expedited review through the program’s development. RP-A501 was generally well tolerated with evidence of restored expression of the deficient LAMP2 protein and durable improvement or stabilization of clinical parameters in the Danon disease patients treated in the phase 1 study.

Data show consistent and robust improvements in multiple parameters including protein expression, reduced autophagic vacuoles, brain natriuretic peptide (BNP), troponin, left ventricular mass and thickness, and improved New York Heart Association (NYHA) class and Kansas City Cardiomyopathy Questionnaire measurements. Notably, these improvements and stabilization of BNP and NYHA class are in stark contrast to BNP increases and NYHA class deterioration observed in a representative sample of pediatric and adolescent natural history patients. Overall, the results demonstrate improvements and/or normalization across multiple quantifiable parameters that cardiologists use in clinical practice to enable risk assessment and treatment decisions.

The initiation of the phase 2 pivotal trial is on track for the second quarter of 2023. As previously disclosed, Rocket anticipates pursuing a single arm, open-label trial with a biomarker-based composite endpoint and a natural history comparator.

Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising pipeline products, including gene therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition.

Similar to Breakthrough Therapy designation, RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early FDA interactions to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the Biologics License Application and other opportunities to expedite development and review. Rocket also holds U.S. Orphan Drug and Rare Pediatric designations for the RP-A501 program.

Photo: Gaurav Shah, CEO of Rocket Pharma

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