Delandistrogene moxeparvovec

« Back 04/04/25 8:44 AM EDT CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr. 4, 2025-- 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.

After the death of a 16-year-old patient, Sarepta and Roche have temporarily paused three trials in Europe of their Duchenne muscular dystrophy gene therapy Elevidys. In response to a request from the European Medicines Agency (EMA) following the death of a 16-year-old patient in the U.S., Sarepta and Roche have temporarily halted three clinical trials in Europe of their Duchenne muscular dystrophy (DMD) gene therapy Elevidys.In a March 31 letter (PDF) from Roche to the World Duchenne Organization, the Swiss drugmaker said that the companies are pausing enrollment and dosing in the studies while continuing to monitor already-enrolled participants and collect data.The paused trials include the Sarepta-sponsored phase 3 Envision study, which is evaluating Elevidys in boys aged 8 to 17; Roche’s phase 2 Envol study, which is investigating Elevidys in babies and newborns; and Sarepta’s Study 104, a phase 1 look at Elevidys in boys ages 4 to 9 with pre-existing antibodies to a particular serotype.The trials have been halted in all EU countries, and the Envol study has been paused in the U.K. The trials are on hold until “analysis into the cause of death is complete,” Roche wrote. Meanwhile, four other U.S.-based Elevidys studies remain ongoing.“While any clinical hold is concerning, we believe the EMA's request to pause the 3 Elevidys studies will likely be temporary and unlikely materially delay their completion timelines or the EMA review of Elevidys' marketing authorization application (MAA),” analysts from Mizuho Securities wrote in a note to investors.In an update on Friday, April 4, Sarepta said that an independent data monitoring committee (DMC) met and concluded 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."Sarepta and Roche plan to submit the DMC's findings to EU regulators "within a week" for review.  Two weeks ago, Sarepta disclosed the patient’s death, which was attributed to acute liver failure. Serious liver injury is a known safety risk of Elevidys.“We cannot rule out the possibility that Elevidys was a contributing factor,” a Sarepta spokesperson told Fierce Pharma last month.The incident brought increased attention to the safety of gene therapies that use adeno-associated viruses (AAVs) as vectors to deliver therapeutic genes. In Elevidys’ case, the administered gene produces microdystrophin, a shortened version of the normal dystrophin protein that’s missing in Duchenne patients.In 2022, Novartis recorded two deaths for its AAV-based, spinal muscular atrophy gene therapy Zolgensma.Although it is not a new safety signal, acute liver failure leading to death is a severity of the disorder not previously reported for Elevidys, which has been provided to more than 800 patients, Sarepta said. The company also reported that testing revealed the deceased patient had a recent cytomegalovirus infection that was identified by his treating physician as a possible contributing factor.Since the report of the patient death, Sarepta’s share price has dropped by 42%.“This is yet another unfortunate development for a story that cannot seem to catch a break,” Leerink wrote on Wednesday, adding that the weight of a 16-year-old patient likely means that he was provided a higher dose than the average Elevidys recipient.“We acknowledge that such severe side effects associated with mortality can certainly be alarming and cause the community to question the risk/benefit of treating older patients. However, we believe that the very low overall incidence is encouraging,” Leerink wrote, adding that its projection of the likelihood of an EU approval remains unchanged at 60%. Elevidys was approved on an accelerated basis in the U.S. in June of 2023 for boys ages 4 and 5. In June of last year, the FDA expanded its label to include all DMD patients aged 4 and up.Both FDA nods stirred controversy, as neither was based on a trial that met its primary endpoint. During development of the treatment, trials were halted in 2018 and 2021 because of safety concerns. Also drawing ire was the $3.2 million price tag for the one-time treatment.Still, sales have scaled up quickly, indicating the unmet need in the indication. In the fourth quarter, Sarepta reported revenue of $383 million from Elevidys, which was a 110% increase from the previous quarter. Leerink Partners projects Elevidys sales to reach $2 billion this year.Editor's note: This story was updated at 9 a.m. EDT on Friday, April 4, to include the latest information from Sarepta.