FDA backs fast-track approval for Regenxbio Duchenne gene therapy

Regenxbio has reached an agreement with the Food and Drug Administration (FDA) for an expedited approval process for its experimental gene therapy aimed at treating Duchenne muscular dystrophy. After discussions with the FDA, the company's ongoing Phase 1/2 study has been extended into a pivotal trial capable of supporting an accelerated approval pathway. This study will involve approximately 30 Duchenne patients, all of whom are at least one year old, and it will not include an active placebo group for comparison. The primary goal of the study is to achieve the production of at least 10% of normal levels of microdystrophin, a small protein believed to benefit Duchenne patients, within three months.

Regenxbio entered the development of gene therapies for Duchenne muscular dystrophy later than other biotechnology companies, but setbacks faced by its competitors have brought it to the forefront as a significant contender. The company's gene therapy, RGX-202, is designed to produce microdystrophin and is delivered using a different type of microscopic virus. RGX-202 generates a larger protein more akin to normal dystrophin, which is expected to improve function, according to CEO Curran Simpson.

Early data indicates promising potential for RGX-202. Patients treated with RGX-202 in Regenxbio's trial have shown higher average levels of microdystrophin compared to those treated with Sarepta Therapeutics' Elevidys. Notably, children aged eight years or older, who are typically in a declining state, exhibited the highest levels of microdystrophin observed in clinical tests for Duchenne gene therapies. Data from five patients, including two aged eight or older, demonstrated either stabilization or improvement in motor function as measured by the North Star Ambulatory Assessment (NSAA) over a period ranging from nine months to one year. No serious adverse events have been reported, with the most common side effects being nausea, vomiting, and fatigue.

Michael Kelly, the chief scientific officer of CureDuchenne, an advocacy group, highlighted the distinct therapeutic profile of RGX-202, suggesting the potential for enhanced benefits compared to other Duchenne gene therapies. CureDuchenne is among several patient groups sponsored by Regenxbio.

Both Sarepta and Pfizer have faced challenges in demonstrating that microdystrophin production can significantly influence the progression of Duchenne muscular dystrophy. Elevidys did not show a meaningful improvement in NSAA scores in two placebo-controlled trials, and Pfizer halted its Duchenne gene therapy development after a Phase 3 trial failed to establish a correlation between microdystrophin levels and functional improvement. These outcomes have raised questions about using microdystrophin as a predictive marker.

Despite the skepticism, Peter Marks, the head of the FDA's gene therapy office, has expressed continued confidence in microdystrophin. At a recent academic symposium, Marks supported the idea of streamlined approvals for microdystrophin gene therapies, which has now been extended to Regenxbio's RGX-202. The agency has endorsed a smaller, open-label trial for Regenxbio, comparing results to historical controls. Secondary goals of the study include timed tests of patients' ability to walk or stand, similar to the objectives in Sarepta and Pfizer's trials. However, NSAA scores have been given less statistical weight in this new trial design. CEO Simpson explained that this decision was based on historical data from other trials rather than FDA guidance, as longer studies might be needed to detect meaningful differences in NSAA scores.

The news is seen positively for other developers of Duchenne gene therapies, alleviating concerns that accelerated approvals might be unattainable. As a result, Regenxbio's shares rose by about 11% in early trading.