RGX-202 (Regenxbio)

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.

Dive Brief:Regenxbio has aligned with the Food and Drug Administration on an abbreviated approval path for an experimental gene therapy the company is developing for Duchenne muscular dystrophy.Following discussions with the agency, an existing Phase 1/2 study has been expanded into a pivotal trial that can support an accelerated approval, Regenxbio said Monday. The study will evaluate Regenxbios gene therapy in about 30 Duchenne patients at least 1 year old and wont include an active placebo as a comparator.Notably, the therapys main study goal will be to produce, after three months, at least 10% of normal levels of a diminutive protein, microdystrophin, thats thought to help Duchenne patients. Previous pivotal studies of Duchenne gene therapies from Pfizer and Sarepta Therapeutics were placebo-controlled and hinged on an evaluation of motor function that, for Regenxbio, is an exploratory measure.Dive Insight:Regenxbio was a latecomer in the biotech industrys development of gene therapies for Duchenne, a deadly muscle-wasting disease with no cure. But stumbles by more advanced competitors have positioned the company as the closest threat to Sarepta Therapeutics Elevidys, which is available for most Duchenne patients despite clinical results that raised doubts about its effectiveness.Like Elevidys, Regenxbios RGX-202 is designed to produce microdystrophin, a tiny version of the muscle-protecting protein Duchenne patients lack. But the therapy is packaged into a different type of microscopic virus. It also produces a larger version of the protein that more closely resembles normal dystrophin, which we expect to lead to improved function, CEO Curran Simpson wrote in an email to BioPharma Dive.The company says early data hints at such potential. The handful of patients treated with RGX-202 at two different dose levels in Regenxbios trial have produced, on average, higher levels of microdystrophin than did those given Elevidys in Sareptas testing. Expression levels in children 8 years or older kids who are expected to already be declining are the highest observed in a clinical test of a Duchenne gene therapy, the company claimed.A snapshot of data Monday from five patients two of whom were 8 or older additionally showed either stabilization or improvement on a measure of motor function called the North Star Ambulatory Assessment, or NSAA, after nine months to one year. No serious adverse events have occurred so far. The most common drug-related side effects were nausea, vomiting and fatigue, the company said.The results show a distinct therapeutic profile with the potential for enhanced benefits compared to other [Duchenne] gene therapies, wrote Michael Kelly, the chief scientific officer of advocacy group CureDuchenne, in an email. (Regenxbio is a sponsor of CureDuchenne as well as other patient groups.)Sarepta and Pfizer have struggled to prove microdystrophin production can alter Duchennes trajectory. Elevidys failed to show a meaningful difference in NSAA scores after a year in two placebo-controlled trials. Pfizer quit developinga Duchenne gene therapy after a failed Phase 3 trial that showed no correlation between microdystrophin levels and function.Those results have fueled questions about microdystrophin as a predictive marker. But Peter Marks, the head of the agencys gene therapy office and the official who overturned other reviewers in approving Elevidys, remains confident. At an academic symposium last week, Marks noted hes not willing to throw out microdystrophin entirely, which signaled the FDA is still open to streamlined approvals for microdystrophin gene therapies, wrote RBC Capital Markets analyst Brian Abrahams.The agency has now agreed to such a path for Regenxbio. In doing so, its endorsed a smaller trial than either Sarepta or Pfizer ran, with an open-label design that compares findings to historical controls. Timed tests of how quickly patients walk or stand up are secondary goals, as they were for Sarepta and Pfizer.NSAA scores have been pushed down in the statistical hierarchy, however. On a conference call with analysts, CEO Simpson said that the decision wasn't driven by the FDA, but was instead based on historical data from other trials. Some analysts have argued, for instance, studies need to run for longer to show a meaningful difference in NSAA scores.The general view has been that [NSAA] is a cruder measure, where there's just less sensitivity to detect a potential drug effect, Simpson said.The news is a net positive for other Duchenne gene therapy developers, alleviating investor concerns that accelerated approvals may be unavailable to other companies, wrote Leerink Partners analyst Joseph Schwartz, in a Monday note to investors.Regenxbio shares climbed about 11% in early trading Monday. '