Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder characterized by progressive muscle degeneration caused by mutations in the dystrophin gene. Z-rostudirsen (DYNE-251) is an investigational exon-51–skipping therapy designed to restore the production of functional dystrophin by enabling targeted delivery of a phosphorodiamidate morpholino oligomer to muscle tissue. Dyne Therapeutics recently reported new cardiopulmonary and long-term clinical results from the Phase 1/2 DELIVER trial evaluating this therapy in individuals with DMD amenable to exon 51 skipping.
The global DELIVER study is a randomized, placebo-controlled clinical trial assessing the safety, tolerability, and efficacy of z-rostudirsen. Participants included ambulatory and non-ambulatory boys aged 4–16 years with confirmed mutations suitable for exon-51 skipping. In the registrational expansion cohort, patients receiving 20 mg/kg z-rostudirsen every four weeks achieved the primary endpoint, demonstrating a statistically significant increase in muscle-content–adjusted dystrophin expression to 5.46% of normal at six months (p<0.0001). This represented approximately a seven-fold increase from baseline dystrophin levels.
In addition to biomarker improvements, patients exhibited functional benefits across multiple clinical endpoints, including measures of mobility and muscle performance. Importantly, cardiopulmonary assessments indicated preservation of lung function at six months, suggesting potential stabilization of respiratory decline—an important determinant of morbidity in DMD. Long-term follow-up data from the study further demonstrated sustained improvements across assessed functional endpoints for up to 24 months, supporting the durability of treatment effects.
Z-rostudirsen also showed a favorable safety and tolerability profile throughout the trial. These results highlight the therapy’s potential to provide clinically meaningful benefit by increasing dystrophin production and improving functional outcomes in patients with DMD amenable to exon-51 skipping. Based on these findings, Dyne Therapeutics plans to submit a Biologics License Application for accelerated approval in the United States in 2026 and initiate a global Phase 3 clinical trial to support broader regulatory approvals.
Overall, the DELIVER trial results suggest that z-rostudirsen may represent a promising disease-modifying therapy capable of improving muscle function and stabilizing cardiopulmonary outcomes in Duchenne muscular dystrophy. Further confirmatory studies will help establish its long-term clinical benefits and role in the evolving therapeutic landscape for DMD.
