Dyne’s Exon Skipper Delivers ‘Best Ever’ Functional Outcomes in Early DMD Study

 

Dyne’s exon-skipping therapy zeleciment rostudirsen resulted in an approximately sevenfold increase in dystrophin levels at six months and elicited functional improvements that are the “best ever” for this treatment class, Stifel analysts said.

Dyne Therapeutics’ investigational therapy zeleciment rostudirsen not only increased dystrophin levels in an early Duchenne muscular dystrophy study but also elicited what Stifel analysts called the “best ever” functional improvements for an exon skipper in this indication.

“The regulatory precedent is overwhelmingly in DYN’s favor,” Stifel added, noting that other Duchenne therapies have been approved based on “marginal” dystrophin effects, even with “limited evidence of clinical efficacy.”

While Dyne’s study was not powered to evaluate functional benefits on a statistical level, the analysts confirmed with the company that the analyses for these outcomes “match the rigor/standard of a registrational study.”

In the registrational expansion cohort of Dyne’s Phase I/II DELIVER study, presented Monday, patients given a monthly dose of 20-mg/kg zeleciment rostudirsen (z-rostudirsen) achieved mean dystrophin expression of 5.46% of normal, adjusted for the patients’ muscle content. This finding represents an approximately sevenfold increase in dystrophin at six months, Stifel said, giving z-rostudirsen a “highly differentiated” efficacy profile.

The analysts pointed out that Dyne’s dystrophin figures “far exceed” those of Sarepta Therapeutics’ exon skipper Exondys 51, which they said hit 0.3% of normal at six months. No head-to-head study between Exondys and z-rostudirsen has been conducted, however, and these cross-study comparisons may not accurately capture the relative efficacies of these therapies, Stifel noted.

Beyond dystrophin, patients on z-rostudirsen also saw notable functional improvements at six months—though DELIVER is not powered for statistical assessments of functional benefits versus placebo. A posthoc analysis nevertheless showed that patients on Dyne’s drug had better time-to-rise and 10-meter walk/run outcomes than placebo counterparts, with nominally significant effects. Z-rostudirsen also boosted participants’ stride velocity and upper limb performance, while also improving their lung function.

With these data, Dyne is planning to file a biologics license application for the drug in the second half of 2026, seeking accelerated approval. If all goes well, and if the FDA grants priority review, the biotech is eyeing an early 2027 launch. Also in the back half of next year, Dyne will launch a Phase III program for z-rostudirsen to validate clinical benefit and support global regulatory filings.

https://www.biospace.com/drug-development/dynes-exon-skipper-delivers-best-ever-functional-outcomes-in-early-dmd-study