Dyne Therapeutics has reported "unprecedented and sustained" functional improvements in patients with Duchenne muscular dystrophy (DMD) treated with its investigational therapy DYNE-251 in the ongoing Phase I/II Deliver trial. The results, presented at the 2025 Muscular Dystrophy Association (MDA) annual meeting in Dallas, Texas, demonstrate significant advancements in both dystrophin expression and mobility measures.
The trial specifically targets DMD patients amenable to exon 51 skipping, a genetic mutation affecting a subset of DMD patients. According to data presented at the conference, patients receiving the registrational dose of 20mg/kg showed a mean absolute dystrophin expression of 8.72% above baseline at the six-month mark, which the company describes as "unprecedented near-full-length dystrophin expression."
Significant Functional Improvements Across Multiple Endpoints
The Deliver trial (NCT03619213) enrolled 88 patients across 33 sites in the United States, Europe, and Asia. Participants were randomized to receive either 20mg/kg of DYNE-251, 10mg/kg of DYNE-251, or placebo administered intravenously.
Both dosing arms demonstrated improvements from baseline in multiple functional endpoints at six and twelve months. These improvements were measured using several validated assessment tools:
- Stride Velocity 95th Centile (SV95C) system
- North Star Ambulatory Assessment (NSAA)
- 10-meter Walk/Run Time
- Time to rise from the floor
"With DYNE-251, we have the opportunity to deliver a durable and redosable therapy demonstrating clinically meaningful and sustained functional improvement in DMD," said John Cox, CEO of Dyne Therapeutics. "The consistency of these new data across multiple endpoints and time points underscores the potential of DYNE-251 to meaningfully address the significant unmet need in Duchenne despite available therapies."
DMD Treatment Landscape and Unmet Needs
Duchenne muscular dystrophy is a progressive, inherited muscle-wasting disease primarily affecting boys. The condition is caused by mutations in the dystrophin gene, resulting in little or no production of the dystrophin protein essential for muscle cell integrity.
Current treatment options for DMD include several approved exon-skipping therapies, which collectively generated approximately $1 billion in sales in 2023, according to GlobalData analysis. However, these therapies are typically mutation-specific, with each addressing only a subset of the DMD patient population.
Exon skipping therapies use antisense oligonucleotides to skip specific sections of DNA during RNA splicing, theoretically enabling the body to produce functional dystrophin. DYNE-251 represents a potential advancement in this approach for patients with exon 51 amenable mutations.
Regulatory Pathway and Market Potential
Dyne Therapeutics is planning for an additional data readout later in 2025, which could position the company to submit for accelerated approval with the U.S. Food and Drug Administration (FDA) in early 2026. The regulatory pathway would leverage dystrophin expression as a surrogate endpoint, a well-established approach for DMD therapies.
"If approved, we believe there is an opportunity for rapid adoption by physicians and currently treated patients, as well as those naïve to therapy," Cox stated.
Market analysis by GlobalData's Pharmaceutical Intelligence Center projects significant revenue potential for DYNE-251 if it reaches the market. Estimates suggest the therapy could generate $5 million by the end of 2025, increasing to $48 million by 2028 and reaching $129 million by 2030.
Competitive DMD Treatment Landscape
The DMD treatment space continues to evolve with several notable clinical trials underway:
Regenxbio is developing RGX-202, a gene therapy designed to deliver a functional copy of the gene encoding microdystrophin, potentially competing with Sarepta's Elevidys in the U.S. market.
Avidity Bioscience's Explore44-OLE trial is examining del-zota, an exon 44 skipping therapy administered intravenously. This addresses approximately 7% of the DMD population with mutations amenable to exon 44 skipping, representing a currently underserved segment.
NS Pharma is seeking European Medicines Agency (EMA) approval for its exon-skipping therapy Viltepso (viltolarsen) based on the Phase III Racer53-X trial. The therapy has already received accelerated approval in the U.S. for patients with exon 53 mutations.
Meanwhile, PepGen has paused the initiation of a new Phase I trial as it awaits data from an ongoing Phase II trial, and the FDA has lifted a two-year clinical hold on Entrada Therapeutics' therapy, ENTR-601-44.
Expert Perspectives on DMD Therapies
Clinical experts emphasize that while increasing dystrophin expression is generally beneficial, the functionality of the produced protein is equally important.
"The idea of more is better is usually true in the context of dystrophin. The flip side of that is, is it functional? Is it doing what you'd like it to?" noted one expert in the field. "You can make a lot of something in the cell, but if it's not located where it's supposed to be and interacting with the other proteins that it's supposed to in a way that's the most effective and functional, then you're not going to see the benefit clinically."
The positive functional outcomes observed in the Deliver trial suggest that the dystrophin produced following DYNE-251 treatment may indeed be functionally beneficial, though longer-term data will be important to confirm durability of effect.
As Dyne Therapeutics advances DYNE-251 toward potential regulatory submission, the therapy represents a promising addition to the evolving treatment landscape for patients with Duchenne muscular dystrophy, particularly those with exon 51 amenable mutations.
