Massachusetts-based Dyne Therapeutics is preparing a regulatory submission to the FDA after reporting encouraging results for its Duchenne muscular dystrophy (DMD) exon 51–skipping therapy—nine years after Sarepta Therapeutics’ Exondys 51 became the first approved treatment for this patient subgroup.
In its phase 1/2 DELIVER study, Dyne enrolled 86 patients with DMD amenable to exon 51 skipping, a mutation that represents roughly 13% of the total DMD population, according to a Dec. 8 company presentation.
Strong dystrophin expression results
Within the trial’s registrational expansion cohort of 32 patients, those who received z-rostudirsen at a dose of 20 mg/kg every four weeks achieved a statistically significant increase in muscle-content–adjusted dystrophin expression compared with baseline. Twenty-four patients received the therapy, while eight received placebo.
At six months, treated patients reached a mean absolute dystrophin level of 5.46% of normal, adjusted for muscle content. The unadjusted figure was 2.87%, the company reported. Dyne highlighted that Sarepta’s Exondys 51 clinical trial showed only 0.3% of normal dystrophin levels after weekly dosing—demonstrating a potential advancement for FDA review.
Although cross-trial comparisons are inherently limited, Dyne noted that Sarepta’s Exondys 51 clinical trial showed only 0.3% of normal dystrophin levels after weekly dosing—highlighting what Dyne describes as a major advancement.
Functional improvements and CEO reaction
Dyne also reported improvements across six functional endpoints, including time to rise, 10-meter walk/run velocity, and lung function measures. CEO Cox said the company plans to submit an accelerated approval application to the FDA in Q2 next year, aiming for a potential U.S. launch in early 2027.
Cox added that the company plans to submit an accelerated approval application to the FDA in Q2 next year, with a potential U.S. launch in early 2027. Dyne is targeting roughly 1,600 U.S. patients, a group he said faces a significant unmet need.
Safety profile and commercial preparations
Dyne reported a positive safety and tolerability profile, with most treatment-emergent adverse events (TEAEs) classified as mild or moderate. The most common TEAEs were fever and headache, and no treatment-related serious adverse events were observed in the registrational cohort. Dyne has hired additional medical, commercial, and CMC experts to support what Cox described as a capital-efficient commercialization strategy ahead of FDA submission.
Preparing for a potential launch, the company has already hired additional medical, commercial, and CMC (chemistry, manufacturing and controls) experts to support what Cox described as a capital-efficient commercialization strategy.
Analyst reaction and market response
In a note to investors, Evercore ISI analyst Gavin Clark-Gartner said the results position Dyne for a strong regulatory path, estimating a 75%–80% probability of approval and projecting up to $700 million in peak annual sales, driven in part by expected substitution of Sarepta’s product.
The company also signaled plans to initiate a phase 3 global trial in 2028 to support broader approvals. Analysts note that Dyne’s findings may set higher expectations for future exon-skipping programs, focusing on durable, higher dystrophin expression and clear functional endpoints for FDA consideration.
Broader DMD landscape
Dyne’s results come shortly after Capricor Therapeutics reported positive outcomes for deramiocel, its DMD cell therapy. In the HOPE-3 trial, patients receiving deramiocel every three months showed notably slower upper-limb functional decline compared with placebo.
Meanwhile, Sarepta, once seen as Dyne’s primary competitor in this mutation class, had aimed to introduce a next-generation therapy to follow Exondys 51 but discontinued development last year due to a safety signal.
The emerging competition in the exon-skipping and gene-modulating treatment space also underscores a larger shift in the DMD market, where developers are increasingly prioritizing measurable dystrophin restoration and functional benefit—criteria that have become more central to regulators since the accelerated approval debates surrounding earlier-generation therapies. Analysts note that Dyne’s results may raise the bar for future exon-skipping programs, pushing the industry toward more durable, higher-expression therapies supported by clearer clinical endpoints. At the same time, payer scrutiny is expected to intensify, as insurers weigh high therapy costs against meaningful improvements in patient mobility and long-term disease progression.
The therapy’s favorable safety profile, combined with measurable functional improvements, could set a new benchmark for exon-skipping approaches in DMD. Experts anticipate that the FDA review process will closely evaluate both dystrophin levels and clinical endpoints, reinforcing the importance of comprehensive, registrational trial design.
