After a year of uncertainty over Sarepta Therapeutics’ Elevidys gene therapy and concerns about the safety of AAV vectors, several companies are advancing new treatments for Duchenne muscular dystrophy (DMD). Sarepta’s Elevidys remains the only approved gene therapy for DMD but faces competition as other therapies move closer to regulatory review.
Debra Miller, founder and CEO of CureDuchenne, highlighted the progress in the field. “I am really thrilled to see the culmination of a lot of our work over the last two decades come forward,” she said, referencing upcoming FDA submissions from REGENXBIO, Capricor Therapeutics, and Avidity Biosciences. Novartis acquired Avidity last October for approximately $12 billion.
CureDuchenne has provided funding to Capricor, Avidity, Sarepta, and Dyne Therapeutics.
Elevidys received a black box warning after two patient deaths due to severe liver injury. As new candidates like REGENXBIO’s RGX-202 and Solid Biosciences’ SGT-003 progress through clinical trials, Sarepta’s market dominance may be challenged.
Michael Kelly, chief scientific officer at CureDuchenne, commented on the industry’s direction: “We’re seeing momentum build into the pipeline.”
Avidity plans to submit a Biologics License Application (BLA) this quarter for its exon-skipper del-zota. Capricor is preparing additional data for its cell therapy deramiocel following positive Phase 3 results in December. REGENXBIO expects pivotal topline data from its RGX-202 gene therapy in the second quarter with a BLA planned for mid-2026. Solid Biosciences continues Phase 1/2 studies with SGT-003.
Dyne is developing zeleciment rostudirsen (z-rostudirsen) for patients eligible for exon 51 skipping. In December, Dyne reported what analysts called the “best ever” functional improvements for an exon-skipper in DMD from a Phase 1/2 trial. The company aims to begin a Phase 3 trial soon and seek accelerated approval.
“There’s a whole plethora of opportunities that are developing at a right pace right now,” Kelly said. “I think the next 12 months will be incredibly exciting [and in] the next 24, we’ll see another handful of drugs approved.”
Novartis’ acquisition of Avidity followed positive discussions with the FDA about del-zota’s regulatory path. Sarah Boyce, president and CEO of Avidity, stated: “The meeting was highly collaborative and provided a clear path forward for our BLA submission.” Analysts expect few obstacles since there are currently no approved exon-44 skipping treatments.
Capricor faced setbacks when its deramiocel therapy was rejected by the FDA last July due to insufficient evidence but later achieved success in its pivotal Phase 3 HOPE-3 trial by demonstrating benefits in upper-limb function and cardiac health. The company is preparing further documentation requested by regulators.
REGENXBIO reported interim data showing robust microdystrophin expression with RGX-202; analysts noted these results were comparable to those seen with Elevidys but cautioned against drawing strong efficacy distinctions due to variability among patients.
Solid Biosciences’ SGT-003 uses an advanced capsid designed to reduce liver targeting—a key concern after Elevidys-related fatalities—and includes unique genetic elements aimed at improving muscle function and endurance. Craig McDonald from UC Davis Health observed that such innovations could lead to better outcomes regarding muscle blood flow and reduced fatigue.
Sarepta recently shared three-year data from its EMBARK trial indicating slowed disease progression among ambulatory patients treated with Elevidys. Louise Rodino-Klapac, president of R&D at Sarepta, said: “Seeing the trajectory continue to widen over time and seeing the true benefit come out is just tremendous and gratifying.” However, some analysts remain unconvinced about Elevidys’ effectiveness based on available data.
Sarepta is also evaluating sirolimus pretreatment in nonambulatory patients as part of efforts to mitigate liver risks associated with gene therapy administration.
Despite advancements, experts caution that none of these therapies represent cures for DMD. Bo Cumbo of Solid Biosciences stated: “We always need better products until this disease state is cured…Physicians need choice. Patients need choice.” McDonald suggested future therapies might enable DMD patients to achieve life expectancies similar to those with Becker muscular dystrophy—averaging around 67 years—but stopped short of calling any current approach curative.
Rodino-Klapac echoed this sentiment: “We have a lot of hope that there will be a cure someday, but I’m very cautious about using the word cure…In my mind you would have to fix the genetic mutation in every single cell,” which she described as unlikely with today’s technology.
She added that earlier treatment could improve outcomes significantly—a goal supported by recent inclusion of DMD in newborn screening panels by U.S. health authorities.
