Sarepta’s gene therapy marches on: UK clears continued dosing in Duchenne Phase 3 trial

Sarepta Therapeutics, Inc., a global leader in precision genetic medicine, has received critical regulatory confirmation from the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom to continue dosing patients enrolled in its pivotal Phase 3 ENVISION study of ELEVIDYS. This development marks a significant step in the company’s ongoing efforts to expand access to gene therapy for individuals affected by Duchenne muscular dystrophy (DMD), particularly in non-ambulatory and older ambulatory patient populations.

The ENVISION trial, officially designated SRP-9001-303, is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of ELEVIDYS (delandistrogene moxeparvovec-rokl), currently the only gene therapy approved for Duchenne patients. The latest UK regulatory feedback ensures that the trial can proceed without interruption—a key milestone for Sarepta as it continues to scale its gene therapy platform in international markets.

What Is ELEVIDYS and How Does It Target Duchenne Muscular Dystrophy?

ELEVIDYS is a single-dose, adeno-associated virus (AAV)-based gene therapy administered intravenously. It is designed to address the root cause of Duchenne muscular dystrophy by delivering a transgene that encodes a shortened but functional version of the dystrophin protein, termed micro-dystrophin. The therapy uses the AAVrh74 vector to introduce the corrective gene into skeletal muscle cells, thereby attempting to restore dystrophin function lost due to DMD gene mutations.

In the United States, ELEVIDYS has received regulatory approval for use in individuals aged four years and older who have a confirmed mutation in the DMD gene. This includes both ambulatory and non-ambulatory patients. For non-ambulatory individuals, the approval is conditional and granted under the U.S. Food and Drug Administration’s accelerated approval pathway, meaning ongoing clinical trials, like ENVISION, are essential to verify its therapeutic benefit.

How Significant Is the MHRA’s Decision for the ENVISION Study?

The MHRA’s guidance to continue dosing in the UK as part of the ENVISION trial provides a much-needed regulatory greenlight amid a complex and evolving clinical trial landscape. This support reaffirms confidence in the safety monitoring measures implemented by Sarepta and its clinical partners and reinforces the agency’s recognition of the trial’s importance in confirming long-term outcomes for gene therapy in Duchenne.

With patient recruitment, dosing continuity, and long-term monitoring being central to validating ELEVIDYS in broader populations, the UK’s regulatory decision enables Sarepta to maintain momentum. The Phase 3 ENVISION study remains critical to the company’s efforts to expand the indication beyond current age and mobility constraints.

What Are the Known Safety Risks of ELEVIDYS Gene Therapy?

Despite its promise, ELEVIDYS is accompanied by a range of potential adverse effects that require close clinical supervision. Among the most concerning are infusion-related reactions, acute serious liver injury, immune-mediated myositis, and myocarditis.

Infusion reactions, including hypersensitivity and even anaphylaxis, have been observed during and shortly after administration. The therapy must therefore be delivered in clinical settings equipped for emergency intervention, and patients must be monitored for at least three hours post-infusion.

Additionally, the therapy has been associated with significant elevations in liver enzymes and bilirubin, which may reflect acute hepatocellular injury. These effects are typically seen within eight weeks of treatment, necessitating intensive liver function testing, particularly in patients with pre-existing liver conditions. Sarepta advises systemic corticosteroids before and after infusion to mitigate such hepatic risks.

Immune-mediated myositis has also been reported, particularly in patients with exon deletions involving exon 8 or exon 9, manifesting as severe muscle weakness, including swallowing difficulties and respiratory symptoms. While limited data are available for certain DMD mutation ranges (exons 1–17 and 59–71), heightened immune reactions remain a possibility in these groups.

Myocarditis, indicated by elevated troponin-I levels and cardiac symptoms such as chest pain or dyspnea, has also emerged as a potential post-treatment complication. Pre- and post-infusion cardiac monitoring is now a recommended component of the ELEVIDYS protocol.

Lastly, pre-existing immunity against the AAVrh74 vector can limit therapeutic efficacy. Sarepta currently recommends against administering ELEVIDYS in patients with anti-AAVrh74 binding antibody titers ≥1:400, as these individuals may not achieve effective transgene expression.

What Is the Clinical and Commercial Importance of ELEVIDYS for Sarepta?

ELEVIDYS represents one of the most advanced therapeutic platforms in Sarepta’s Duchenne muscular dystrophy pipeline. As the first gene therapy approved for this indication, its commercial rollout in the U.S. is being closely watched by analysts, investors, and regulatory authorities globally.

The therapy has emerged as a cornerstone of Sarepta’s long-term strategy to redefine treatment paradigms for rare neuromuscular diseases. The continuation of the ENVISION trial plays a dual role—not only validating the therapy’s efficacy in expanded populations but also helping to convert accelerated approvals into full authorizations in multiple jurisdictions.

Sarepta remains one of the most closely followed companies in the rare disease space, with an expanding pipeline in genetic medicine spanning limb-girdle muscular dystrophies (LGMDs), central nervous system disorders, and cardiac-related conditions. Its lead in DMD has drawn both scientific praise and regulatory scrutiny, particularly around the long-term durability and cost-effectiveness of gene therapy platforms.

How Are Investors Responding to Sarepta’s Clinical Progress?

Following the MHRA’s greenlight, early investor sentiment appears cautiously optimistic. Sarepta Therapeutics, Inc. (NASDAQ: SRPT) continues to draw strong institutional interest given its positioning at the forefront of genetic therapeutics. However, the company’s stock performance has historically been volatile, often tied to binary clinical milestones and regulatory outcomes.

With ongoing concerns around gene therapy safety, manufacturing scale-up, and reimbursement hurdles, investor confidence hinges on clear demonstration of long-term benefit and manageable safety profiles. The ENVISION study’s progression may help address some of these variables, especially as Sarepta seeks to convert accelerated approvals into durable market positions.

The market is also watching closely for updates from the confirmatory studies that will determine the therapy’s future eligibility for full approval in both ambulatory and non-ambulatory patients. While positive UK feedback is encouraging, much will depend on trial outcomes and future regulatory actions across other global health agencies.

What’s Next for Sarepta and the Future of Duchenne Gene Therapy?

Looking ahead, Sarepta is expected to intensify its clinical development efforts not only with ELEVIDYS but also with next-generation platforms targeting broader genetic disease cohorts. The company’s regulatory strategy—spanning the U.S., UK, and other geographies—reflects a multi-pronged approach to advancing gene therapy accessibility in a commercially sustainable way.

The MHRA’s decision to allow continued dosing in the UK adds a significant vote of confidence in the robustness of Sarepta’s safety monitoring and trial design. If outcomes from ENVISION and other ongoing studies validate long-term clinical benefit, Sarepta could further solidify its leadership in the field and accelerate the adoption of gene therapy for other neuromuscular and systemic rare diseases.

While challenges remain—especially in safety management, pricing, and access—Sarepta’s ability to navigate complex regulatory environments and deliver therapeutic innovation positions it as a key player in the evolving gene therapy landscape.