On June 15, 2025, Sarepta, the manufacturer of Elevidys, issued a press release that announced a safety update for Elevidys and steps to strengthen safety in non-ambulatory patients with DMD. This statement was made in response to a second reported case of fatal acute liver failure, both of which occurred in non-ambulatory patients with DMD. As a result of this recent safety concern, Sarepta began taking proactive steps to mitigate the risk of acute liver failure in this patient population. Shipments of Elevidys for non-ambulatory patients have since been suspended while additional safety mitigation strategies are assessed. Additionally, dosing in the ENVISION trial, evaluating Elevidys in older ambulatory and non-ambulatory patients with DMD, was voluntarily paused.¹ Sarepta has also assembled a group of independent leading experts in DMD and liver health to review an enhanced immunosuppression regimen for Elevidys. This proposed regimen includes sirolimus use in non-ambulatory patients to regulate liver enzyme levels.¹˒² A proposal for data collection for this regimen in cohort 8 of the ENDEAVOR study will be submitted to the FDA in order to re-establish dosing in this patient population.² Real-world data opportunities through investigator- led trials in the ambulatory population are also being reviewed. However, recommendations from the panel will be subject to FDA review. As of the press release from June 15, 2025, no changes in treatment were made for the ambulatory DMD patient population.¹

On June 24, 2025, the FDA issued a safety communication regarding the two reports of fatal acute liver failure following treatment with Elevidys in non-ambulatory pediatric male patients with DMD. The safety communication stated that the deaths appeared to be related to Elevidys treatment. The two patients presented with elevated liver transaminases and were hospitalized less than two months after being treated with Elevidys. As a result, the FDA announced it was investigating these risks as well as the need for additional regulatory action.³ Moreover, in a July 16, 2025 press release, Sarepta announced that the FDA requested that a black box warning for acute liver injury and acute liver failure be included in the Elevidys label.² Prime KOLs agree that the addition of a black box warning to the Elevidys label is necessary. 

An additional death occurred in a 51-year-old non-ambulatory patient with Limb-Girdle Muscular Dystrophy (LGMD) in a Phase 1 trial for the investigational gene therapy SRP-9004.⁴ This death appears to have also been as a result of acute liver failure.⁵ Though this investigational gene therapy has a different manufacturing process and dose from Elevidys, Prime KOLs highlight that both Elevidys and SRP-9004 share the same AAVrh74 vector. While Sarepta announced a few days prior that it would pause most gene therapy development programs for LGMD due to reprioritization,² on July 18, 2025, the FDA announced the investigational gene therapy clinical trials for LGMD were placed on clinical hold following the three deaths.⁵ The FDA also requested Sarepta to voluntarily halt all shipments of Elevidys.⁴˒⁵ Additionally, the FDA revoked the platform technology designation for Sarepta’s AAVrh74 Platform Technology due to insufficient evidence to determine that this technology could be incorporated in more than one drug without an adverse effect on safety.⁵ On July 21, 2025, Sarepta notified the FDA of the decision to voluntarily and temporarily pause all shipments of Elevidys for DMD in the U.S. effective at the close of business on July 22, 2025.⁶

Days later, the FDA reported an investigation regarding the June 7, 2025, death of an 8-year-old boy who received Elevidys.⁷ Then, on July 28, 2025, the FDA recommended removal of the voluntary hold on Elevidys in ambulatory patients. This announcement noted that the FDA concluded the death of the 8-year-old boy was unrelated to the gene therapy product. The FDA is continuing to work with Sarepta to further evaluate Elevidys use in the non-ambulatory patient population, which at this time, remains on hold.⁸ 

In addition to the news with Elevidys, there have been additional updates in the DMD landscape regarding the pipeline agent deramiocel, which is being investigated for the treatment of DMD cardiomyopathy. On July 11, 2025, Capricor, the manufacturer of deramiocel, announced it received a Complete Response Letter (CRL) from the FDA pertaining to its Biologics License Application (BLA) for deramiocel. The FDA cited that the BLA does not meet the statutory requirement for substantial evidence of effectiveness as well as there being a need for additional clinical data. The CRL also cited specific components in the Chemistry, Manufacturing and Controls (CMC) section of the application; however, Capricor states that many of these items have been addressed but were not reviewed by the FDA due to timing. Capricor plans to resubmit its BLA to include the requested data from the ongoing Phase 3 HOPE-3 trial in Q3 2025 in order to provide additional evidence of effectiveness.⁹