Sarepta Therapeutics has provided additional safety data on its gene therapy Elevidys as a Duchenne muscular dystrophy patient group petitions the FDA to update the medicine’s label.
Altogether, eight patients had passed away following treatment with Elevidys as of the data cutoff on July 22, Sarepta said in its Aug. 14 response to an FDA citizen petition.
Except for the two previously reported deaths from acute liver failure, the other six cases have all been determined to be unrelated to the Duchenne treatment, according to the company.
The causes of death for those patients include disease progression, pneumothorax (when air leaks into the chest and the lung collapses) either from pulmonary bleb rupture or secondary to bacterial pneumonia, anoxic brain injury accompanied by multiorgan failure, acute respiratory failure with cardiac arrest, and influenza.
Liver toxicity, a known side effect of Elevidys because of immune responses to the drug’s viral vector, has become an even more concerning issue after two deaths were reported in March and June, plus a third death tied to an investigational muscular dystrophy drug using the same gene therapy technology. All three patients were not able to walk because of the stage of the disease.
For Elevidys specifically, among the 1,043 patients treated with the gene therapy in clinical trials or the commercial setting worldwide, the overall rate of hospitalization due to acute liver injury was 5.8%, according to Sarepta’s analysis of the data.
After Elevidys’ initial FDA approval in 2023, 5.8% of 552 ambulatory patients and 8.4% of 107 non-ambulatory patients in the U.S. were hospitalized due to acute liver injury (ALI), according to the company.
“This analysis of currently available data shows that the vast majority of ALI adverse events following treatment with Elevidys are non-serious and do not result in hospitalization,” Sarepta said in its response letter. “Importantly, the hospitalization rate remains consistently low (single digits) for all patients treated, regardless of ambulatory status or whether they were treated in a clinical trial or in the post-market setting.”
The ALI hospitalization rate calculated by Sarepta is lower than the 9.8% produced by Citi analysts using the FDA Adverse Event Reporting System (FAERS). While Citi came up with the number by counting all hospital admissions that overlapped with ALI, Sarepta’s calculation appears to be restricted to patients who were admitted specifically for ALI, the Citi team said in a Sunday note to clients.
In its letter, Sarepta highlighted multiple flaws of the FAERS database, including delays in updates and the lack of indication whether or not any death can be chalked up to treatment. To back its argument, Sarepta pointed to death events that were logged in FAERS for other therapeutics, including for other cell and gene therapies, that do not seem to match the public perceptions of those drugs.
The citizen petition was filed in late June by the Jett Foundation, which offers support to families impacted by Duchenne. The nonprofit requested that the FDA add a boxed warning on Elevidys’ label regarding the risk of death and hospitalization from liver and cardiac injury.
Sarepta has already agreed to the FDA’s request to add a black box warning for acute liver injury and failure. But the Massachusetts biopharma noted that no treatment-related fatalities with Elevidys due to cardiac injury have been recorded to date. The company said it sees “no evidence of a negative impact” from Elevidys treatment on cardiac function based on an analysis of 218 patients with a median follow-up of 2.1 years.
Besides the boxed warning, the Jett Foundation also requested additional language on Elevidys’ label to make it clear that patients who receive the product may not be eligible for other adeno-associated virus-based gene therapies in the future, as well as a communication plan for healthcare professionals outlining these risks.
Following reports of the patient deaths, Sarepta, the Duchenne community and the FDA went through a chaotic period earlier this summer. First, Sarepta stopped shipments of Elevidys to non-ambulatory patients before the FDA asked the company to pause treatment in all patients. Shortly after that, the agency changed its stance to allow continued delivery to ambulatory patients.
Around this time, patient groups and conservatives attacked Vinay Prasad, M.D., the FDA’s top official overseeing cell and gene therapy, for his regulatory approach. Prasad subsequently left the agency on the heels of the FDA’s reversal on Elevidys, only to return a short time later.
Sarepta, for its part, faced criticism over its lack of upfront disclosures of the safety issues. The death related to the other investigational muscular dystrophy therapy and the death of an 8-year-old Elevidys patient as a result of influenza were first publicly reported by media outlets.
Sarepta’s latest safety data release indicates “a favorable evolution in corporate messaging,” but the possibility of future fatalities—combined with the return of Prasad, who had criticized Elevidys before—continues to pose a threat to the company, Citi analysts said in their Sunday note.