Regenxbio has aligned with the FDA on an accelerated approval path for its investigational gene therapy, RGX-202, designed to treat Duchenne muscular dystrophy (DMD). This decision follows discussions with the agency, expanding an existing Phase 1/2 study into a pivotal trial that could support accelerated approval. The trial will evaluate RGX-202 in approximately 30 Duchenne patients, all at least one year old, without the use of an active placebo comparator. This regulatory endorsement marks a significant step forward in the development of new treatments for this debilitating disease.
Trial Design and Endpoints
The primary endpoint of Regenxbio's pivotal study is to achieve at least 10% of normal levels of microdystrophin, a truncated protein thought to benefit Duchenne patients, after three months of treatment. Notably, previous pivotal studies of Duchenne gene therapies from Pfizer and Sarepta Therapeutics relied on placebo-controlled designs and motor function assessments. For Regenxbio, motor function will be an exploratory measure.
RGX-202: Aims for Improved Dystrophin Production
RGX-202, similar to Sarepta Therapeutics’ Elevidys, aims to produce microdystrophin, a smaller version of the dystrophin protein that Duchenne patients lack. However, RGX-202 utilizes a different viral vector and produces a larger microdystrophin protein that more closely resembles the normal dystrophin. According to CEO Curran Simpson, this approach is expected to lead to improved function.
Early Clinical Data
Early data from Regenxbio's trial suggests promising potential. Patients treated with RGX-202 at varying doses have shown higher average levels of microdystrophin production compared to those treated with Elevidys in Sarepta's trials. The company reports that expression levels in children aged eight years and older—a population expected to be declining—are the highest observed in any clinical test of a Duchenne gene therapy.
A snapshot of data from five patients, including two aged eight or older, indicated either stabilization or improvement in motor function, as measured by the North Star Ambulatory Assessment (NSAA), after nine months to one year. The most common drug-related side effects reported were nausea, vomiting, and fatigue, with no serious adverse events observed.
Industry Impact and Future Outlook
Michael Kelly, the chief scientific officer of CureDuchenne, noted that the results demonstrate a "distinct therapeutic profile with the potential for enhanced benefits compared to other [Duchenne] gene therapies."
The FDA's decision to grant an accelerated approval pathway for Regenxbio's RGX-202 is viewed as a positive sign for other Duchenne gene therapy developers, alleviating concerns about the availability of accelerated approvals in the field. Regenxbio shares experienced an increase of approximately 11% in early trading following the announcement.
