StemCell Therapy

In a short statement, Sarepta said the patient suffered acute liver failure after receiving Elevidys, the only approved gene therapy for the disease. Liver damage is a known risk of treatment with Elevidys as well as other gene therapies that are built around a type of modified virus. The death is the first reported among the more than 800 people in clinical testing and commercially who been treated with the therapy, however.

According to Sarepta, testing showed the patient had a recent infection with cytomegalovirus, a common virus that for most people doesnt cause symptoms, but can lead to serious health issues in those with weakened immune systems. A treating physician cited the infection as a possible contributing factor to the death, as cytomegalovirus can infect and damage the liver, leading to hepatitis.

The company reported the death to study investigators, physicians and health authorities. It plans to update Elevidys prescribing information to appropriately represent the event.

Patient safety and well-being are Sareptas top priority, the company said. We continue to gather and analyze the information from this event.

Sarepta shares lost more than a quarter of their value, sliding to about $75 apiece in Tuesday morning trading.

The product of decades of research, Elevidys is the only gene therapy available for Duchenne, a progressive and fatal muscle-wasting condition. The Food and Drug Administration first approved Elevidys in mid-2023 for a narrow population. One year later, it was cleared for use in a broader group of Duchenne patients.

Sales of Elevidys have grown as a result, making the treatment one of the few gene therapies to achieve commercial success. Sarepta reported about $384 million in Elevidys sales last quarter, and some analysts have predicted they will top $2 billion this year.

Yet the FDAs approval came despite mixed results in clinical testing that left questions about Elevidys benefits. The therapy got an OK only after Peter Marks, who heads one of the agencys main drug review offices, overruled other reviewers, citing effects on secondary study measures and comparisons to historical data that suggested Elevidyss effects are meaningful.

While the viruses used to construct Elevidys are a preferred tool for delivering gene therapies, they are also associated with certain safety risks that have drawn concern from the FDA in recent years. Among those risks are liver toxicity, which in certain cases in studies of other treatments has led to serious health problems. Four children who received a gene therapy from Audentes Therapeutics in testing later died, and two fatal cases of acute liver failure were reported among patients treated with Novartis Zolgensma.

At a meeting about gene therapy safety three years ago, experts recommended stringent monitoring for preexisting liver conditions, and placing an upper limit on the doses tested. Drugmakers need higher doses of gene therapy to treat neuromuscular diseases, since the treatment must travel through the bloodstream to reach the right tissue.

Elevidys FDA labeling already includes a warning about the risk of an increase in certain liver enzymes that can signal organ damage. Patients are given steroids before and after treatment to lower the risk, and the agency advises doctors conduct weekly blood draws for three months to monitor liver enzyme levels.

At a medical conference this week, Sarepta shared a safety analysis from 156 patients who received Elevidys. Among those, eight cases of liver abnormalities were observed, though Sarepta said there were no clinically significant cases after 90 days. All liver-related adverse events included in that analysis later resolved.

In a statement, Parent Project Muscular Dystrophy, a prominent patient advocacy group, noted that the incident highlights the urgent need to fully understand the risks associated with gene therapy in our current therapeutic landscape to ensure patient safety.

The death could also mean the benefit/risk calculation of Elevidys has worsened, wrote Jefferies analyst Andrew Tsai.

The case could give physicians further pause when considering whether to start treatment, especially considering perceptions of relatively modest clinical benefits, wrote Brian Abrahams, an analyst at RBC Capital Markets, in a note to clients.

In her own note, Cantor Fitzgerald analyst Kristen Kluska wrote that, while patients will still seek gene therapy and some might continue to view the benefits as outweighing the risks, doctors might use extra caution before starting someone on Elevidys.

Elevidys may also soon have other gene therapy competition. Regenxbio has advanced a treatment into late-stage testing, while Solid Biosciences has said it intends to discuss with the FDA this year an accelerated approval pathway for its experimental treatment.

Editors note: This story has been updated to include a statement from Parent Project Muscular Dystrophy.

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Duchenne patient dies after receiving Sarepta gene therapy