Racing toward a pivotal study, Rocket Pharmaceuticals has received a show of confidence from the FDA in the potential of its gene therapy treatment for a fatal genetic cardiac disease.
The adeno-associated virus-based gene therapy, RP-A501, found itself in the crosshairs of the FDA two years ago when the agency imposed a clinical hold on an early-phase clinical trial in Danon disease. But, having escaped from the hold later in 2021 and delivered data last year, Rocket has now persuaded the FDA of the potential of the gene therapy.
Tuesday, the biotech revealed the receipt of a regenerative medicine advanced therapy (RMAT) nod for RP-A501. The FDA awards the designation to gene therapies and other advanced products that, based on preliminary clinical evidence, have the potential to address serious or life-threatening diseases.
As a gene therapy in development in Danon, a genetic disease with a median overall survival of 19 years in males, RP-A501 meets two of the criteria for RMAT designation by definition. The only question was whether preliminary clinical evidence indicated the candidate could actually treat Danon.
Rocket generated data to answer that question in a phase 1 clinical trial that linked the gene therapy to the improvement or stabilization of cardiac biomarkers including the hormone BNP and the protein troponin I. The biotech compared the results to data from a sample of pediatric and adolescent external comparators to show how the biomarkers in RP-A501 recipients diverged from natural Danon history.
Based on the data, Rocket plans to move into a pivotal phase 2 trial. Last month, the biotech said it had reached agreement with the FDA on key elements of the clinical trial, including the use of a single-arm, open-label design with natural history data as an external comparator and the potential for accelerated approval based on a composite biomarker-driven endpoint.
The FDA agrees with Rocket that endpoints such as the six-minute walk test are not appropriate for Danon, according to the biotech. But, at the time of the earlier update, the agency was still debating the specific components of the composite endpoint, including expression of the protein LAMP2 and the duration of the trial and time to endpoint.
Rocket is collecting natural history data from multiple sources to serve as the external comparator. A prospective natural history study of 10 patients got underway in 2019. Rocket is also sourcing data from two retrospective studies, one assessment of 118 people in the U.S. that began in 2006, and one EU study that got underway last year and aims to enroll 120 people.