Dyne Submits BLA for Z-Rostudirsen in Exon 51 Skipping Duchenne Muscular Dystrophy

Dyne Therapeutics has submitted a biologics license application (BLA) to the FDA seeking accelerated approval of zeleciment rostudirsen (z-rostudirsen; formerly DYNE-251) for patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping, marking a major regulatory milestone for the investigational exon-skipping therapy.¹

The submission is supported by findings from the phase 1/2 DELIVER trial (NCT05524883), in which treatment with z-rostudirsen led to statistically significant increases in dystrophin production alongside improvements across multiple functional endpoints and a favorable safety profile. Dyne has requested Priority Review, which could shorten the FDA review timeline from 10 months to 6 months if granted. The company continues to anticipate a potential U.S. launch in the first quarter of 2027.

“This is a significant milestone for both our company and the DMD community,” John Cox, president and chief executive officer of Dyne, said in a statement.¹ “Despite the availability of approved therapies, there remains a significant unmet need in DMD for treatments with compelling efficacy, a favorable safety profile and improved dosing convenience. Z-rostudirsen was developed with the goal of delivering functional improvement with lower treatment burden for those living with this progressive disease.”

DMD is a rare, X-linked neuromuscular disorder caused by mutations in the dystrophin gene, leading to progressive muscle degeneration, loss of ambulation, cardiomyopathy, respiratory decline, and premature mortality. Exon-skipping therapies are designed to restore the reading frame of the dystrophin gene, enabling production of a shortened but functional dystrophin protein. Approximately 13% of patients with DMD harbor mutations amenable to exon 51 skipping.²

Z-rostudirsen is a phosphorodiamidate morpholino oligomer (PMO) conjugated to a transferrin receptor 1 (TfR1)-targeting antigen-binding fragment (Fab), a design intended to enhance delivery into muscle tissue and potentially the central nervous system. Unlike earlier exon-skipping therapies that require weekly dosing, Dyne’s proposed regimen involves intravenous administration every 4 weeks at 20 mg/kg.

The BLA submission builds on topline data released in December 2025 from the registrational expansion cohort (REC) of DELIVER, where z-rostudirsen met its primary endpoint in dystrophin expression. In the cohort, 32 ambulatory and nonambulatory boys with exon 51-amenable DMD were enrolled, with 24 randomized to receive z-rostudirsen and 8 assigned placebo.³

In the trial, investigators observed a statistically significant increase in muscle content-adjusted dystrophin expression to 5.46% of normal relative to baseline at 6 months (P <.0001). When not adjusted for muscle content, mean absolute dystrophin expression reached 2.87% of normal, substantially higher than levels historically reported with currently approved weekly exon 51-skipping therapies.

“The Duchenne community has long awaited therapies that deliver meaningful and sustained functional improvement,” Perry Shieh, MD, PhD, neurologist and professor of neurology and pediatrics at UCLA, said in a prior statement.³ “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.”

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Functional findings from DELIVER also showed improvement relative to pooled placebo controls across all 6 prespecified clinical endpoints. Notably, Time to Rise (TTR) velocity and 10-Meter Walk/Run (10MWR) velocity demonstrated statistically significant improvements compared with placebo at 6 months (nominal P <.05). Improvements were additionally observed in North Star Ambulatory Assessment (NSAA) scores, stride velocity 95th centile (SV95C), Performance of Upper Limb (PUL2.0), and forced vital capacity percent predicted (FVC%p).

Longer-term extension data further suggested sustained functional benefit through 18 and 24 months across multiple outcome measures. Safety findings remained generally favorable, with most treatment-emergent adverse events reported as mild or moderate. The most commonly observed related adverse events included pyrexia and headache.

Just days prior to the BLA submission, Dyne announced initiation of the global phase 3 FORZETTO confirmatory trial, designed in alignment with the FDA to support conversion from accelerated to traditional approval.⁴ The randomized, placebo-controlled study will enroll approximately 90 ambulatory boys aged 4 to 18 years with exon 51-amenable DMD who will receive either z-rostudirsen 20 mg/kg or placebo every 4 weeks over 72 weeks.

The primary endpoint of FORZETTO is change from baseline in rise-from-floor velocity at Week 73, with additional secondary measures assessing mobility, pulmonary function, and patient-reported outcomes. Dyne noted that the study may also support future regulatory submissions outside the United States.

Beyond z-rostudirsen, the company is advancing a broader exon-skipping pipeline targeting exons 53, 45, 44, and 55, reflecting a strategy aimed at addressing multiple genetically defined DMD populations.

In 2025, the FDA granted breakthrough therapy designation to z-rostudirsen following encouraging findings from the DELIVER trial. In response to the designation, Doug Kerr, MD, PhD, spoke with NeurologyLive® about the therapeutic rationale and mechanism of z-rostudirsen in Duchenne muscular dystrophy (DMD). Kerr, chief medical officer at Dyne Therapeutics, highlighted previously reported data from both the early- and late-stage cohorts, emphasizing sustained, clinically meaningful functional improvements alongside robust dystrophin expression.

REFERENCES
1. Dyne Therapeutics Announces Submission of Biologics License Application (BLA) to U.S. FDA for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD). News release. Dyne Therapeutics. May 26, 2026. Accessed May 27, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-submission-biologics-license
2. Duchenne muscular dystrophy. National Institute of Neurological Disorders and Stroke. Updated March 25, 2025. Accessed May 26, 2026. https://www.ninds.nih.gov/health-information/disorders/duchenne-muscular-dystrophy
3. Dyne Therapeutics Announces Positive Topline Results from Phase 1/2 DELIVER Trial of Z-Rostudirsen in Duchenne Muscular Dystrophy (DMD). News release. December 8, 2025. Accessed May 26, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-positive-topline-results-phase-12
4. 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 May 26, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-initiation-phase-3-forzetto-trial