Sarepta Shares ELEVIDYS Safety Update, Implements Steps to Enhance Safety for Non-Ambulatory Duchenne Patients

Sarepta Therapeutics (SRPT) is taking proactive steps to address safety concerns related to its gene therapy ELEVIDYS, the only FDA-approved treatment for Duchenne muscular dystrophy (DMD). The company announced a series of measures following a second reported case of acute liver failure (ALF) resulting in death in a non-ambulatory patient, prompting immediate action to strengthen the safety profile of its flagship product.

Putting Safety First: Key Initiatives

The company is implementing a multipronged approach to mitigate the risk of ALF, underscoring its commitment to patient safety and regulatory compliance.

Refining the Immunosuppressive Strategy: Sarepta is enlisting a panel of independent experts in Duchenne and liver health to devise an enhanced immunosuppression regimen for ELEVIDYS. The proposed regimen, which includes sirolimus, is backed by preclinical data suggesting its effectiveness in moderating liver enzyme elevations – a critical factor in minimizing potential safety issues. Sarepta plans to work with the FDA on the implementation of the new regimen.

Pausing Shipments. Sarepta is temporarily suspending ELEVIDYS shipments for non-ambulatory patients while the enhanced immunosuppressive regimen is evaluated, and regulatory approvals secured.

For ambulatory patients, current treatment protocols, including pre- and post-infusion corticosteroids and monitoring, will continue unchanged.

ENVISION Study Paused. Due to the same concerns, Sarepta has voluntarily paused dosing in the ENVISION clinical study (SRP-9001-303), with the support of the FDA. This will allow for the incorporation of the enhanced immunosuppression regimen for the non-ambulatory patient cohort. Regulatory alignment is required before the study will resume.

ENVISION, a global trial, is evaluating ELEVIDYS in older ambulatory and non-ambulatory individuals living with Duchenne muscular dystrophy. In the U.S., it functions as the confirmatory trial under the FDA’s accelerated approval pathway for non-ambulatory patients, marking a significant step in validating the therapy’s long-term efficacy and safety.

According to Louise Rodino-Klapac, Ph.D., chief scientific officer and head of research & development, Sarepta, “Our paramount priority is the safety and well-being of the patients we serve… With more than 900 individuals treated to-date, we know how much hope families place in new treatment options like ELEVIDYS – and we are committed to honoring that hope by acting swiftly, guided by scientific rigor and the insights of leading experts, to strengthen safety for all future patients.”

Long-Term Safety and Transparency

Sarepta’s commitment to patient safety extends beyond immediate actions. The company is maintaining transparency, reporting the event to the FDA and global health authorities, and will continue to provide updates on the regulatory review, with possible label changes. While elevated liver enzymes are a known class effect common with AAV-based gene therapies, the exact mechanism behind AAV-related liver toxicity remains unclear. Current evidence suggests it is likely driven by an adaptive immune response.

Investor Call Scheduled

Sarepta will host a conference call on June 16, 2025, at 8:00 a.m. Eastern Time to discuss these developments and provide a broader update on its business strategy.

About ELEVIDYS (delandistrogene moxeparvovec-rokl)

ELEVIDYS is a one-time, adeno-associated virus (AAV)-based gene transfer therapy given via intravenous infusion. It’s designed to address Duchenne muscular dystrophy (DMD) at its source — mutations in the *DMD* gene, that block the creation of the dystrophin protein. The therapy delivers a transgene that codes for ELEVIDYS micro-dystrophin, which helps to restore muscle function and slow disease progression.

The drug is approved for DMD treatment in individuals aged 4 years and older.

• For ambulatory patients with a confirmed mutation in the *DMD* gene.

• For non-ambulatory patients with a confirmed mutation in the *DMD* gene.

The DMD indication in non-ambulatory patients is approved under accelerated approval based on the expression in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION: ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the *DMD* gene.

WARNINGS AND PRECAUTIONS:

Infusion-related Reactions:

• Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration. Closely monitor patients during administration and for at least 3 hours after the end of infusion. If symptoms of infusion-related reactions occur, slow, or stop the infusion and give appropriate treatment. Once symptoms resolve, the infusion may be restarted at a lower rate.

• ELEVIDYS should be administered in a setting where treatment for infusion-related reactions is immediately available.

• Discontinue infusion for anaphylaxis.

Acute Serious Liver Injury:

• Acute serious liver injury has been observed with ELEVIDYS, and administration may result in elevations of liver enzymes (such as GGT, GLDH, ALT, AST) or total bilirubin, typically seen within 8 weeks.

• Patients with preexisting liver impairment, chronic hepatic condition, or acute liver disease (e.g., acute hepatic viral infection) may be at higher risk of acute serious liver injury. Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled.

• Prior to ELEVIDYS administration, perform liver enzyme test and monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT, and total bilirubin levels return to near baseline levels).

• Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion. Adjust corticosteroid regimen when indicated. If acute serious liver injury is suspected, consultation with a specialist is recommended.

Immune-mediated Myositis:

• In clinical trials, immune-mediated myositis has been observed approximately 1 month following ELEVIDYS infusion in patients with deletion mutations involving exon 8 and/or exon 9 in the DMD gene. Symptoms of severe muscle weakness, including dysphagia, dyspnea, and hypophonia, were observed.

• Limited data are available for ELEVIDYS treatment in patients with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to 71. Patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction.

• Advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea, or hypophonia, as these may be symptoms of myositis. Consider additional immunomodulatory treatment (immunosuppressants [e.g., calcineurin-inhibitor] in addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur.

Myocarditis:

• Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYS infusion in clinical trials.

• If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Monitor troponin-I before ELEVIDYS infusion and weekly for the first month following infusion and continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath.

• Advise patients to contact a physician immediately if they experience cardiac symptoms.

Preexisting Immunity against AAVrh74:

• In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with ELEVIDYS, all patients developed anti-AAVrh74 antibodies.

• Perform baseline testing for presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYS administration.

• ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers greater than or equal to 1:400.

Adverse Reactions:

• The most common adverse reactions (incidence ≥5%) reported in clinical studies were vomiting, nausea, liver injury, pyrexia, and thrombocytopenia.

Report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Sarepta Therapeutics at 1-888-SAREPTA (1-888-727-3782).

For further information, please see the full Prescribing Information.

About Sarepta Therapeutics

Sarepta is focused on creating precision genetic medicines for rare diseases. The company has a strong foothold in Duchenne muscular dystrophy (Duchenne) and limb-girdle muscular dystrophies (LGMDs) and is continuously expanding its portfolio of programs across muscle, central nervous system, and cardiac diseases. For additional information, please go to www.sarepta.com or follow the company on LinkedIn, X, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the ‘For Investors’ section of our website at www.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Forward-Looking Statements

This statement contains “forward-looking statements.” Any statements that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements relating to our future operations, research and development programs, clinical trials, ELEVIDYS, the potential benefits of an enhanced immunosuppression regimen in dosing in non-ambulatory patients, and expected plans and milestones, including providing additional updates as appropriate and engaging with regulators on an enhanced immunosuppressive regimen for dosing in non-ambulatory patients.

Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: different methodologies, assumptions and applications we use to assess particular safety or efficacy parameters may yield different statistical results, and even if we believe the data collected from clinical trials are positive, these data may not be sufficient to support approval by the FDA or other global regulatory authorities; success in clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and the results of future research may not be consistent with past positive results or with advisory committee recommendations, or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; our products or product candidates may be perceived as insufficiently effective, unsafe or may result in unforeseen adverse events; our products or product candidates may cause undesirable side effects that result in significant negative consequences following any marketing approval; we may not be able to comply with all FDA requests in a timely manner or at all; the possible impact of regulations and regulatory decisions by the FDA and other regulatory agencies on our business; and those risks identified under the heading “Risk Factors” in our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company, which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Company’s business, results of operations and the trading price of Sarepta’s common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained herein. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof, except as required by law.

Source: Sarepta Therapeutics, Inc.