Delandistrogene moxeparvovec

Regenxbio's stock saw a 5% bump on Monday after announcing positive early-stage data for its Duchenne muscular dystrophy (DMD) gene therapy RGX-202, with the company receiving encouraging FDA feedback that could expedite a possible regulatory approval down the road.The biotech said all five participants in its Phase I/II AFFINITY DUCHENNE trial demonstrated "evidence of positively impacting disease trajectory," including stable or improved function on the North Star Ambulatory Assessment (NSAA) and timed function tests, which assess the time it took to stand or to walk/run 10 metres.Regenxbio said the trial has expanded into an open-label pivotal Phase I/II/III study expected to support an FDA filing in 2026 using the accelerated approval pathway.RGX-202 is a microdystrophin gene therapy with the functional elements of the C-terminal domain found in naturally occurring dystrophin. Regenxbio says the data reveal functional improvements "exceeding natural history benchmarks."The readout covered 12-month results from three patients at dose level 1 (1x10¹⁴ GC/kg), aged 4 to 10, and nine-month results from two patients at the pivotal second dose level (2x10¹⁴ GC/kg), aged 8 and 12. Results were measured against external natural history controls matched for age and baseline function."We see a clear drug effect at dose level 1 and we see this very enhanced effect at dose level 2," said CEO Curran Simpson during an investor call.'Performing beautifully'An outcome that particularly stood out was the performance of a 12-year-old patient who improved his NSAA score by 10 points. The company noted there was no matched natural history external control data for this patient on this particular measure."He's one of two patients that we have nine months of data on, so anything that I could say is presumptuous at best, but we do recognise that he is performing so well, way beyond what we would have ever expected," commented clinical development lead Jahannaz Dastgir on a call with analysts."Any child entering into this study who's a little bit older will probably fall on the higher end of better function for Duchenne patients," she said, adding that "he's performing beautifully, but obviously had a deficit that he was able to improve upon by 10 points in the North Star." Dastgir indicated that the 12-year-old, like all children enrolled in the study, will be closely monitored to identify any unique factors that could explain why some participants respond so well to the treatment.By contrast, the eight-year-old patient on the second dose level achieved only a 1-point improvement on NSAA compared to baseline, and a 2.8-point improvement versus external natural history controls, where the condition worsened over the same timeframe.Meanwhile, the biomarker data showed RGX-202 microdystrophin expression levels among the "highest reported" across approved or investigational gene therapies in ambulatory patients aged 8 and older, according to the company. At 12 weeks, patients demonstrated mean microdystrophin expression ranging from 10.4% to 39.7% of normal control levels in these older patients.The therapy's safety profile appeared promising, with no serious adverse events reported across 11 treated patients. The most common side effects were nausea, vomiting, and fatigue.Challenging Elevidys' leadIf it does succeed, RGX-202 could become the second DMD gene therapy cleared in the US after Sarepta Therapeutics' Elevidys (delandistrogene moxeparvovec-rokl), which was initially granted an accelerated approval last year with a restricted label. This past June, the FDA expanded the label to include both non-ambulatory boys and those aged four years and older. Elevidys generated US market sales of $191 million in the third quarter, and Sarepta recently reiterated its projection for it to deliver $2 billion in sales next year.Meanwhile, a gene therapy programme from Pfizer was discontinued earlier this year after a failed pivotal trial. Fordadistrogene movaparvovec missed the primary endpoint of the Phase III CIFFREO study, as well as several key secondary endpoints.