RARE Daily

EMA Grants PRIME Designation to Rocket’s Gene Therapy for Danon Disease

June 1, 2023

Rare Daily Staff

The European Medicines Agency granted Priority Medicines (PRIME) designation to Rocket Pharmaceutical’s RP-A501, the company’s experimental gene therapy for the treatment of rare and fatal cardiomyopathy Danon Disease.

The EMA granted PRIME designation to Rocket based on positive safety and efficacy data from the phase 1 clinical trial of RP-A501 in patients with Danon Disease and the potential of RP-A501 to meet the high unmet medical need in this population.

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 United States 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 is a high unmet medical need for patients with Danon Disease.

RP-A501 is Rocket’s first AAV program. It is a gene therapy product consisting of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a functional version of the human LAMP2B transgene (AAV9.LAMP2B) which is administered as a single intravenous infusion. The company said RP-A501 has the potential to restore normal cardiac function in patients with Danon Disease.

PRIME designation offers the benefits of early and enhanced support from the EMA for the development of medicines that target unmet medical needs, as well as the opportunity for an accelerated review of the marketing application. The U.S. Food and Drug Administration recently granted Rocket Regenerative Medicine Advanced Therapy (RMAT) designation for its RP-A501 program, which also holds Fast Track, Orphan Drug and Rare Pediatric designations.

Results from the phase 1 trial represent one of the most comprehensive investigational gene therapy datasets for any cardiac condition. RP-A501 was associated with a favorable safety profile. The data demonstrated consistent and robust improvements in multiple clinical and highly relevant laboratory parameters including LAMP-2 protein expression, reduced autophagic vacuoles, brain natriuretic peptide (BNP), high sensitivity troponin I, and left ventricular mass and wall thickness.

In addition, there was improvement in symptoms, as assessed by New York Heart Association class and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire. Notably, the improvements and stabilization of BNP in Phase 1 patients were in direct contrast to worsening patterns observed in patients enrolled in a concurrent, prospective natural history study. The results demonstrated improvements and/or normalization across multiple quantifiable parameters that cardiologists use in clinical practice to enable risk assessment and treatment decisions.

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