Today, things got worse for Sarepta Therapeutics, in that it was revealed there was a 3rd patient who died; however, this was a patient who was taking the investigational limb-girdle muscular dystrophy (LGMD) gene therapy. Unlike the other two deaths linked to acute liver failure (ALF) in two non-ambulatory Duchenne Muscular Dystrophy (DMD) patients with ELEVIDYS. This was a 51-year-old man who had non-ambulatory LGMD and took a single dose of SRP-9004.
These patient deaths put into question whether Sarepta will continue to be able to potentially even ship this drug for ambulatory DMD patients. For now, there has been no mention of removing this gene therapy for this group of patients. However, it was working with the FDA about possibly running cohort 8 of the ENDEAVOR study (Study SRP-9001-103) with the addition of immunosuppressive sirolimus to this therapy in order to re-establish dosing in the non-ambulant DMD patient population.
The updated label of ELEVIDYS in order to accomplish this move to reopen the ability to market to this non-ambulatory patient population was laid out in the company’s restructuring to reprioritize its pipeline and reduce its workforce as well. In this restructuring, it was revealed that it would still move forward with its LGMD gene therapy SRP-9003 for patients with disease type 2E/R4. Even though the third patient death who had LGMD was that of SRP-9004, this could possibly put doubt on whether or not the company could obtain U.S. marketing approval of this program. It laid out that it would file a Biologics License Application (BLA) of SRP-9003 in the 2nd half of 2025, and this remains the case for now, unless it changes otherwise.
The pipeline dealing with its gene therapy programs of ELEVIDYS in treating patients with DMD and then investigational LGMD therapies appears to be at risk. While it is true that these two gene therapies are not one and the same, even having different dosing and manufacturing processes, they use the same AAV viral vector rAAVrh74 (delivery vehicle). Another reason why the future of ELIVIDYS remains a risk is because of an update that Sarepta provided in terms of an informal request from the FDA. That is, it received an informal request from the U.S. Food and Drug Administration (FDA) to voluntarily stop all shipments of ELEVIDYS for the treatment of patients with DMD in the United States.
Despite the informal request by the FDA for it to halt shipments of ELEVIDYS, the company stated that it will continue to do so for ambulatory DMD patients. It also stated that it notified the FDA about the patient death of ALF with LGMD on June 20, 2025, and then it followed this up with a notification to this U.S. agency on July 3, 2025. What remains a mystery now is what will happen next with this gene therapy that is currently helping some DMD patients (ambulatory ones). The hope is that Sarepta is able to convince the FDA to keep ELEVIDYS on the market for treating these patients, as it is the only gene therapy approved for them, but there is no assurance of this with all the recent events that have transpired.
What could possibly save the company is that it is in the process of developing RNA interference (RNAi) drugs targeting other disorders like idiopathic pulmonary fibrosis (IPF), myotonic dystrophy type 1 (DM1), facioscapulohumeral muscular dystrophy (FSHD), Huntington’s disease (HD), and others. It expects to report data from some of these programs in phase 1/2 studies in the 2nd half of 2025. However, it remains to be seen if it is able to achieve positive results from one of these indications. If it does, then it could have a chance at recovering as a biotech with respect to its pipeline.