FDA Accepts BLA for Z-Rostudirsen in DMD, Sets January PDUFA Date

The FDA has accepted for review the biologics license application (BLA) for zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) for Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping.¹ The agency granted Priority Review and set a PDUFA target action date of January 21, 2027. Dyne Therapeutics continues to expect a potential U.S. launch in the first quarter of 2027, assuming approval on the anticipated timeline.¹

"This milestone represents significant progress toward our goal of delivering functional improvement for those living with DMD amenable to exon 51 skipping," John Cox, president and chief executive officer of Dyne, said in a statement.¹ "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."

The submission seeks Accelerated Approval based on dystrophin as a surrogate endpoint, a pathway already established for other exon-skipping therapies in DMD.

Data supporting the application

The BLA is built on the registrational expansion cohort (REC) of the global phase 1/2 DELIVER trial (NCT05524883), which enrolled 32 ambulatory and nonambulatory boys with DMD aged 4 to 16 years with mutations amenable to exon 51 skipping; 24 were randomized to z-rostudirsen 20 mg/kg every 4 weeks and 8 to placebo.²

The REC met its primary endpoint, showing a statistically significant increase in muscle content-adjusted dystrophin expression to 5.46% of normal relative to baseline at 6 months (P < .0001). Unadjusted for muscle content, mean absolute dystrophin expression reached 2.87% of normal, compared with 0.3% historically reported with weekly standard-of-care exon 51-skipping therapy.²

Functional improvement relative to pooled placebo was observed across all 6 prespecified clinical endpoints at 6 months, including Time to Rise Velocity and 10-Meter Walk/Run Velocity (nominal P < .05 for both), alongside gains in the North Star Ambulatory Assessment, Stride Velocity 95th Centile, Performance of Upper Limb, and forced vital capacity percent predicted.

"The Duchenne community has long awaited therapies that deliver meaningful and sustained functional improvement," principal investigator Perry Shieh, MD, PhD, a neurologist and professor of neurology and pediatrics at the David Geffen School of Medicine at UCLA, said in a statement.² "Our scientific understanding of the disease has led to a strong belief that restoring a sufficient level of near-full-length dystrophin expression in individuals with DMD could have the potential to significantly alter the trajectory of this disease."

Safety data, drawn from 86 participants followed for up to 36 months and representing 113 patient-years of exposure, showed a safety profile consistent with prior observations. Most related treatment-emergent adverse events were mild or moderate, with pyrexia and headache the most common.

Regulatory path and pipeline

Z-rostudirsen, a phosphorodiamidate morpholino oligomer conjugated to a transferrin receptor 1-targeting antibody fragment, is designed to enable near-full length dystrophin production in muscle and the central nervous system via monthly IV dosing rather than the weekly regimen required by currently approved exon 51-skipping therapies. It has previously received Breakthrough Therapy, Fast Track, and Rare Pediatric Disease designations from the FDA, along with Orphan Drug designation from the FDA, EMA, and Japan's Ministry of Health, Labour and Welfare.¹

The therapy continues to be evaluated in DELIVER's long-term extension and in the global confirmatory phase 3 FORZETTO trial, which will enroll roughly 90 ambulatory boys aged 4 to 18 years and is designed to support conversion from accelerated to traditional approval.³ Exon 51-amenable mutations account for approximately 13% of the roughly 12,000 individuals with DMD in the U.S.⁴ Beyond z-rostudirsen, Dyne is advancing four additional exon-skipping candidates targeting exons 53, 45, 44, and 55.¹

REFERENCES
1. Dyne Therapeutics Announces U.S. FDA Acceptance of Biologics License Application (BLA) for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD). News release. Dyne Therapeutics. July 20, 2026. Accessed July 20, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-us-fda-acceptance-biologics-license
2. Dyne Therapeutics Announces Positive Topline Results from Phase 1/2 DELIVER Trial of Z-Rostudirsen in Duchenne Muscular Dystrophy (DMD). News release. Dyne Therapeutics. December 8, 2025. Accessed July 20, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-positive-topline-results-phase-12
3. Dyne Therapeutics Announces Initiation of Phase 3 FORZETTO Trial of Z-Rostudirsen in Duchenne Muscular Dystrophy (DMD) Ahead of Planned BLA Submission for U.S. Accelerated Approval. News release. Dyne Therapeutics. May 20, 2026. Accessed July 20, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-initiation-phase-3-forzetto-trial
4. Duchenne muscular dystrophy. National Institute of Neurological Disorders and Stroke. Updated March 25, 2025. Accessed July 20, 2026. https://www.ninds.nih.gov/health-information/disorders/duchenne-muscular-dystrophy