Regenxbio has received FDA endorsement for an accelerated approval pathway for its investigational gene therapy, RGX-202, targeting Duchenne muscular dystrophy. This decision follows discussions with the agency, leading to the expansion of an existing Phase 1/2 study into a pivotal trial. The trial aims to enroll around 30 Duchenne patients aged one year and older and will not include an active placebo comparator.
The primary endpoint of the study is to achieve a minimum of 10% of normal microdystrophin protein levels three months post-treatment. Microdystrophin, a truncated version of the dystrophin protein, is crucial for muscle protection and is deficient in Duchenne patients. Previous pivotal studies by Pfizer and Sarepta Therapeutics for their Duchenne gene therapies relied on placebo-controlled designs and motor function assessments, which Regenxbio will use as exploratory measures.
RGX-202: A Potential Improvement Over Existing Therapies
RGX-202 is designed to produce microdystrophin, similar to Sarepta Therapeutics' Elevidys. However, RGX-202 utilizes a different adeno-associated virus (AAV) vector and produces a larger microdystrophin protein that more closely resembles the native dystrophin. According to Regenxbio CEO Curran Simpson, this could lead to improved function. Early data from the trial indicates that patients treated with RGX-202, at varying doses, have demonstrated higher average microdystrophin levels compared to those observed in Sarepta's Elevidys trials. Notably, expression levels in patients aged eight years and older, who are typically experiencing functional decline, are reported to be the highest observed in any clinical trial for Duchenne gene therapy.
A data snapshot from five patients, including two aged eight or older, revealed 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 adverse events were nausea, vomiting, and fatigue, with no serious adverse events reported.
FDA's Perspective on Microdystrophin
Despite previous controversies surrounding the use of microdystrophin expression as a predictive marker, Peter Marks, head of the FDA's gene therapy office, has expressed continued confidence in its potential. This stance is reflected in the FDA's willingness to grant accelerated approval pathways for microdystrophin-based gene therapies like RGX-202. The agency's decision to accept a smaller, open-label trial design, compared to the larger, placebo-controlled trials conducted by Sarepta and Pfizer, further underscores this confidence.
While timed tests of walking speed and standing ability remain secondary endpoints, NSAA scores have been moved lower in the statistical hierarchy. CEO Simpson explained that this decision was based on historical data from other trials, suggesting that NSAA may be a less sensitive measure for detecting drug effects in certain contexts. Leerink Partners analyst Joseph Schwartz noted that this development is a positive sign for other Duchenne gene therapy developers, alleviating concerns about the availability of accelerated approvals.
