Sarepta Therapeutics Provides Update on ELEVIDYS

Rhea-AI Summary

Sarepta Therapeutics (NASDAQ:SRPT) announced a temporary halt in recruitment and dosing for certain clinical studies of ELEVIDYS, their approved gene therapy for Duchenne muscular dystrophy. This follows a safety update on acute liver failure from March 18.

The independent data monitoring committee (DMC) reviewed the adverse event on April 3 and concluded that the overall benefit-risk profile remains favorable to continue dosing. The affected studies include SRP-9001-302 (ENVOL), SRP-9001-303 (ENVISION), and SRP-9001-104.

Sarepta and Roche will submit their response to EU regulators within a week. The company maintains that monitoring and data collection for already-enrolled participants continues, and they do not anticipate material impact on study timelines.

Positive

• DMC confirms favorable benefit-risk profile for ELEVIDYS
• No material impact expected on study timelines
• Monitoring and data collection continues for enrolled participants

Negative

• Temporary halt in recruitment and dosing for multiple clinical trials
• Safety concerns regarding acute liver failure require regulatory review
• EU regulatory review process could potentially delay progress

Insights

Biotech Regulatory Analyst

Sarepta's announcement of a temporary halt to ELEVIDYS clinical trials represents a regulatory hurdle with mixed implications. Following a previously reported case of acute liver failure, EU regulators requested a DMC review, resulting in paused enrollment and dosing across three clinical studies despite the company having an approved product on the market.

The positive DMC assessment that the benefit-risk profile remains favorable without protocol modifications provides significant reassurance. However, this remains subject to EU regulatory review, creating a period of uncertainty. Regulatory authorities often take more conservative positions than monitoring committees, particularly with serious adverse events like liver failure.

The statement that timelines won't be materially impacted suggests Sarepta expects a swift resolution, but regulatory interactions frequently extend beyond company projections. The affected studies include two key trials (ENVOL and ENVISION) that are crucial for maintaining ELEVIDYS's accelerated approval status and potentially expanding its label.

While monitoring continues for already-enrolled participants, the pause introduces execution risk and potential delays in generating confirmatory efficacy data needed for full approval. For a therapy with serious safety warnings including acute liver injury, myositis, and myocarditis, any new safety signals require careful evaluation and could potentially lead to enhanced monitoring requirements or labeling adjustments even if the trials resume without protocol changes.

Gene Therapy Specialist

This temporary halt in ELEVIDYS clinical trials highlights the inherent safety challenges with AAV-based gene therapies. The reported case of acute liver failure that triggered EU regulatory scrutiny isn't entirely surprising given the therapy's established safety profile, which already includes warnings for acute serious liver injury.

What's critically important here is the independent DMC's assessment that the benefit-risk profile remains favorable without protocol modifications. This suggests the liver failure case may be an isolated event rather than a systemic safety concern requiring program-wide adjustments. For a serious condition like Duchenne muscular dystrophy with treatment options, regulators typically accept higher risks when balanced against meaningful efficacy.

The affected studies are central to Sarepta's ELEVIDYS program - particularly ENVISION, which likely serves as the confirmatory trial for continued accelerated approval. While the company maintains there won't be material timeline impacts, even short delays in studies for an already-marketed product create commercial uncertainty.

The detailed safety warnings in the release - particularly regarding liver monitoring for 3 months post-infusion - indicate Sarepta is properly managing known risks. However, the addition of any new safety requirements following this review could add complexity to the therapy's administration protocol, potentially impacting its adoption in clinical practice and ultimate commercial potential.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, shared the following update related to ELEVIDYS (delandistrogene moxeparvovec-rokl), the only approved gene therapy in patients with Duchenne muscular dystrophy.

Following the safety update on acute liver failure that was issued on March 18, European Union (EU) reference member country authorities requested that the independent data monitoring committee (DMC) meet to review the adverse event. While the analysis is being finalized, recruitment and dosing in certain clinical studies of ELEVIDYS are temporarily halted.

The independent DMC met on April 3 and concurred that based on the totality of evidence, the overall benefit-risk profile remains favorable to continue dosing in the paused clinical trials without changes to the study protocols. At the request of EU regulators, Sarepta and Roche will submit this information in a response to the temporary halt within a week. Evaluation of the submission and the subsequent decision for lifting the temporary halt will follow the EU regulatory process.

The clinical studies affected by the temporary halt are Study SRP-9001-302 (ENVOL), Study SRP-9001-303 (ENVISION) and Study SRP-9001-104. Monitoring and data collection for already-enrolled participants continues, and we do not anticipate a material impact on the timeline for these studies.

About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle.

ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.

• For patients who are ambulatory and have a confirmed mutation in the DMD gene
• For patients who are non-ambulatory and have a confirmed mutation in the DMD gene.

The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) 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 on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (Duchenne) and limb-girdle muscular dystrophies (LGMDs) and are building a robust portfolio of programs across muscle, central nervous system, and cardiac diseases. For more information, please visit www.sarepta.com or follow us 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, the potential timing of clinical trials and the potential benefits and risks of ELEVIDYS.

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; 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; the possible impact of regulatory decisions by, and any halts imposed by, regulatory agencies on our business; and those risks identified under the heading “Risk Factors” in our most recent Annual Report on Form 10-K for the year ended December 31, 2024 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250404491162/en/

Investor Contact:

Ian Estepan

617-274-4052

iestepan@sarepta.com

Media Contacts:

Tracy Sorrentino

617-301-8566

tsorrentino@sarepta.com

Kara Hoeger

617-710-3898

KHoeger@sarepta.com

Source: Sarepta Therapeutics, Inc.

FAQ

What caused the temporary halt in ELEVIDYS clinical trials by Sarepta Therapeutics (SRPT)?

The halt followed a safety update on acute liver failure from March 18, prompting EU regulators to request a DMC review of the adverse event.

Which clinical trials of SRPT's ELEVIDYS are affected by the temporary halt?

The affected studies are SRP-9001-302 (ENVOL), SRP-9001-303 (ENVISION), and SRP-9001-104.

What was the DMC's conclusion about ELEVIDYS safety on April 3, 2024?

The independent DMC concluded that the benefit-risk profile remains favorable to continue dosing in the paused clinical trials without protocol changes.

What are the main safety concerns for ELEVIDYS treatment?

Key safety concerns include acute liver injury, immune-mediated myositis, myocarditis, infusion-related reactions, and potential issues with pre-existing AAVrh74 antibodies.