One patient with Duchenne muscular dystrophy (DMD) has passed away following treatment with Sarepta Therapeutics’ gene therapy Elevidys, the biotech said (PDF) Tuesday.
The patient suffered acute liver failure. A Sarepta spokesperson identified the patient as a 16-year-old male but didn’t disclose when and where the incident took place.
“We are collecting additional information, but based on the current information from the treating physician, including the time since treatment and the clinical course, we cannot rule out the possibility that Elevidys was a contributing factor,” the spokesperson said.
The incident once again brings 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.
Acute serious liver injury is a known safety risk of Elevidys and some other AAV-based gene therapies. Back in 2022, Novartis recorded two deaths from acute liver failure after patients were treated with its spinal muscular atrophy gene therapy Zolgensma.
For Elevidys, the deceased patient also had a recent cytomegalovirus (CMV) infection, which can infect and damage the liver. The patient’s treating physician identified CMV as a possible contributing factor to the death, according to Sarepta.
This is the first time an Elevidys-treated patient has developed acute liver failure leading to death, according to Sarepta. The gene therapy has been administered to more than 800 patients in clinical trials or in the commercial setting, the company said.
Sarepta argues that the benefit-risk of Elevidys remains favorable. But the death case could spark renewed concerns over the efficacy-safety balance of Elevidys following its controversial approvals at the FDA.
On separate occasions, Peter Marks, M.D., Ph.D., the director of the FDA’s Center for Biologics Evaluation and Research, overruled internal objections from agency reviewers to grant Elevidys its initial accelerated approval and an expanded label last year that covers most Duchenne patients in the U.S.
To critics, the approvals are built on shaky ground because the one-time gene therapy missed the mark in two clinical trials.
In the phase 3 Embark trial that won Elevidys its broad label that covers all DMD patients ages 4 and older, the Sarepta med was found not significantly better than placebo on a measure of motor function called the North Star Ambulatory Assessment (NSAA) after one year. For its part, the company argued there was a “clinically meaningful” improvement seen in the study.
Earlier this year, Sarepta provided updated two-year data from part 1 of the Embark trial showing that Elevidys takers scored 2.88 points higher on NSAA versus matched external controls. In part 2 of the study, which enrolled patients who crossed over to receive Elevidys after initially receiving a placebo, Elevidys improved NSAA by 2.34 points versus external comparators.
The efficacy data shortfall and the high price of Elevidys have previously drawn Sarepta criticism from families affected by DMD.
“You haven’t delivered any of this evidence you’re supposed to have for your $3.2 million drug,” Catherine Collins, mother of a DMD patient, was recorded telling a Sarepta exec at a Parent Project Muscular Dystrophy event last year.
“We’re the people who give you the millions of dollars but you’re not giving us anything back, which is facts, data and science,” Collins said, as quoted by Stat.
Following the expanded FDA approval in late June, Elevidys brought in $384 million sales for Sarepta during the last three months of 2024. During the prior quarter, sales were $181 million. The increase reflects the high unmet need in the disease and the lack of treatment options.
Sarepta’s commercial partner, Roche, recorded 184 million Swiss francs in total Elevidys sales last year outside the U.S.
The biotech does not expect the latest death event will have an impact on demand for Elevidys, the spokesperson said. Previously, Zolgensma’s reported deaths didn’t appear to affect its uptake among SMA patients.
Sarepta has reported the case to health authorities, and it “intends to update the prescribing information to appropriately represent this event,” according to the spokesperson. Given that liver toxicity is reflected as a boxed warning on Zolgensma’s U.S. label, such a warning can be expected for Elevidys.
By mid-morning Tuesday, Sarepta’s share price fell by about 21% to $79.42. In a note to clients, analysts at William Blair said the death was “unfortunate" but the stock reaction was “overblown,” noting that they “see this event as unlikely to affect patient/physician interest in Elevidys in the near term.”