After a patient taking the Duchenne muscular dystrophy gene therapy Elevydis died of liver injury, Sarepta will update the label to reflect the safety signal.
A patient taking Sarepta Therapeutics’ approved Duchenne muscular dystrophy gene therapy Elevidys has died, the biotech announced Tuesday.
The death was linked to acute liver failure, which Sarepta maintains is not a new safety signal. Elevidys and other gene therapies that use adeno-associated virus (AAV) vectors are known to have acute liver injury as a side effect and that risk is highlighted as an adverse event in Elevidys’ prescribing information. Sarepta also insists that the gene therapy’s benefit-risk profile “remains positive.”
Sarepta has reported the death to the relevant health authorities and will update Elevidys’ label to “appropriately represent this event,” the biotech noted in its Tuesday release. The company’s stock plunged around 22% as the markets opened on Tuesday to $78.54, down from $101.35 at the previous market close.
The death “represents a severity of acute liver injury not previously reported for Elevidys,” Sarepta noted. The patient had also tested positive for cytomegalovirus (CMV) infection, which can damage the liver and is “a possible contributing factor” to the death, according to the announcement. Sarepta expressed “profound” sadness over the death.
BMO Capital Markets said in a Tuesday note that despite the death, “we think Elevidys’ benefit still outweighs the risk,” pointing to the patient’s CMV infection as a mitigating actor. BMO also highlighted two patients who died after taking Novartis’ spinal musclar atrophy gene therapy drug Zolgensma in 2022. That drug today generates north of $1 billion annually. In another note on Tuesday, analysts at Jefferies said they expect the patient death will “pressure” Sarepta’s stock as “uncertainty around [Elevidys’] safety will loom—unless [Sarepta] deems the death not to be drug-related.”
Nevertheless, Jefferies points to a potential bright spot for Sarepta, noting that liver injury typically occurs within the first 90 days of Elevidys treatment. “Presumably, the patient was dosed with Elevidys recently,” the analysts continued, adding “mitigating these types of events could be manageable with very careful monitoring.”
Jefferies also pointed out that “the unmet need in DMD [Duchenne muscular dystrophy] remains high,” which could be a “bull case” for Sarepta.
Elevidys isn’t the first Duchenne therapy to be linked to a fatal outcome. In 2021, Pfizer was forced to suspend a Phase Ib trial for its investigational gene therapy PF-06939926—which would later get renamed as fordadistrogene movaparvovec—following the death of a non-ambulatory patient.
Three years later, in March 2024, the same therapy resulted in another patient death in the Phase II DAYLIGHT trial. A month later, fordadistrogene movaparvovec failed to significantly improve motor function versus placebo in the Phase III CIFFREO trial in Duchenne. Pfizer ultimately axed the gene therapy.
Meanwhile, in November 2022, an FDA-sanctioned trial from the non-profit biotech Cure Rare Disease for a CRISPR-based Duchenne therapy also led to the death of the only enrolled patient. A study in September 2023 pointed to the AAV vector as the potential cause of the mortality, which could have triggered an immune reaction in the patient.
