FDA Grants Priority Review to Dyne’s z-Rostudirsen for DMD

Dyne Therapeutics announced that the US Food and Drug Administration has accepted for review its Biologics License Application seeking Accelerated Approval of z-rostudirsen (DYNE-251) for the treatment of individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The application has been granted Priority Review, reducing the standard review timeline from 10 months to six months, and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 21, 2027. The BLA is supported by dystrophin production as a surrogate endpoint, which is intended to support accelerated approval for therapies addressing serious conditions with unmet medical needs.

Z-rostudirsen has previously received several FDA expedited regulatory designations, including Breakthrough Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations for the treatment of DMD amenable to exon 51 skipping. According to Dyne, these designations are intended to facilitate development and expedite regulatory review for therapies targeting serious rare diseases with unmet medical need.

DELIVER trial formed the basis of the BLA

The BLA is supported by data from the global Phase 1/2 DELIVER trial (NCT05524883). In the registrational expansion cohort, treatment with 20 mg/kg of z-rostudirsen administered intravenously every four weeks resulted in a robust and statistically significant increase in dystrophin production, meeting the study’s primary endpoint. Functional improvements were also observed across multiple clinical endpoints, including rise-from-floor velocity, North Star Ambulatory Assessment (NSAA), stride velocity, and pulmonary function, while demonstrating a favorable safety profile.

Long-term follow-up data from DELIVER further demonstrated sustained functional improvements for up to 24 months across multiple mobility and respiratory endpoints. Most treatment-related adverse events were mild or moderate, with pyrexia and headache being the most commonly reported treatment-related events. No treatment-related serious adverse events were observed in the registrational expansion cohort.

Phase 3 FORZETTO trial underway

Z-rostudirsen continues to be evaluated in the global confirmatory Phase 3 FORZETTO trial (NCT07608432). The randomized, double-blind, placebo-controlled study is expected to enroll approximately 90 ambulatory male participants aged 4–18 years with DMD amenable to exon 51 skipping. Participants will receive z-rostudirsen or placebo every four weeks over a 72-week treatment period. The primary endpoint is change from baseline in rise-from-floor velocity at Week 73, while secondary endpoints include NSAA score, stride velocity, 10 meter walk/run velocity, four-stair climb velocity, forced vital capacity, and patient-reported outcomes. The study is intended to serve as the confirmatory trial for conversion from accelerated to traditional approval and to support regulatory submissions outside the United States.

A Potential Shift in DMD Treatment Delivery

DMD is a rare, severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to a complete or near-complete lack of dystrophin—a protein vital for maintaining muscle structure and function. The condition affects roughly 12,000 people in the U.S. and 16,000 in the EU, typically causing progressive muscle weakness, loss of mobility, and eventually cardiac and respiratory complications. Z-rostudirsen aims to overcome traditional delivery challenges using Dyne’s proprietary FORCE™ platform. The therapy conjugates a phosphorodiamidate morpholino oligomer (PMO) to an antigen-binding fragment (Fab) that targets the transferrin receptor 1 (TfR1). This targeted mechanism is engineered to enable broad delivery to muscle tissue and the central nervous system (CNS), encouraging the production of near-full-length dystrophin to deliver functional improvements. “With z-rostudirsen, we set out to advance the treatment paradigm in DMD by combining a robust increase in near-full length dystrophin with broad delivery to relevant tissues,” said John Cox, president and chief executive officer of Dyne. “With a potential approval in six months, we are continuing our launch preparations with the aim of making z-rostudirsen available as quickly as possible.”

Regulatory review marks a key milestone

The FDA’s acceptance of the BLA represents an important regulatory milestone for Dyne Therapeutics as it advances its lead DMD program toward potential commercialization. If approved, z-rostudirsen could provide a new treatment option for patients with exon 51 amenable DMD by combining robust dystrophin restoration with clinically meaningful functional improvements. With a PDUFA target action date of January 21, 2027, the FDA’s decision will determine whether z-rostudirsen becomes the next exon-skipping therapy available for this rare neuromuscular disease.

References

Dyne Therapeutics Announces U.S. FDA Acceptance of Biologics License Application (BLA) for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD). July 2026.