Sarepta Stops Shipments of Elevidys For Non-Ambulatory DMD Patients

Sarepta Therapeutics has temporarily suspended the shipment of the gene therapy Elevidys (delandistrogene moxeparvovec-rokl) for non-ambulatory patients with Duchenne muscular dystrophy after a second patient has died from acute liver failure. The company has also paused a phase 3 study that is a confirmatory trial for the gene therapy’s use with non-ambulatory patients.

Serapta officials said this morning they are putting together an independent group of experts in Duchenne and liver health to consider an enhanced immunosuppression regimen for Elevidys. The panel will evaluate the data for adding the immunosuppression drug sirolimus to patients with Duchenne who are non-ambulatory. Additionally, company executives plan to meet with FDA officials to discuss adding a sirolimus regimen for these patients.

Doug Ingram

“Our goal is to move as rapidly as possible to implement a risk mitigation strategy, which would allow us first to safely commence study 303 and continue providing what I believe to be a life-enhancing therapy to boys and young men who have Duchenne muscular dystrophy in the United States,” Doug Ingram, president and CEO of Sarepta, said during an investor call this morning

Duchenne muscular dystrophy is a serious genetic disorder that causes progressive muscle weakness and deterioration, especially in the skeletal muscles that control movement. An estimated 20,000 children worldwide are diagnosed with DMD each year.

Elevidys is a one-time, intravenous treatment that uses adeno-associated virus (AAV) technology to deliver a gene designed to produce a shortened form of the dystrophin protein, known as Elevidys micro-dystrophin, directly to skeletal muscle.

The therapy is approved for patients aged 4 and older with a confirmed mutation in the DMD gene, both those who can walk and those who cannot. For non-ambulatory patients, the approval is accelerated and requires a confirmatory trial.

Elevidys is priced at $3.2 million per dose. Sarepta had $1.7 billion in net product revenue in 2024, almost half of which — $821 million — came from Elevidys. Ingram said during today’s investor call the company will reassess revenue guidance and the impact on the second quarter.

In the investor call, company officials said that more than 900 patients across a range of ages have been dosed with Elevidys over the last seven years, with 150 patients in the non-ambulatory group.

“Historically, we have not had a signal that we need our safety committee to conclude additional measures were necessary or appropriate,” Ingram said. “However, following this second tragic event, we have immediately taken steps with the goal of further enhancing the safety profile of Elevidys in the non-ambulatory patient population.”

Sarepta had announced in March that a patient had died from acute liver failure.

Related: Death of Elevidys Patient Rattles Duchenne Community

Louise Rodino-Klapac, Ph.D.

Acute liver injury is a known possible side effect of Elevidys and other AAV-mediated gene therapies. Elevidys triggers a T cell, an immediate immune response. This response then causes inflammation, which in severe cases can lead to acute liver injuries, and in very rare cases, acute liver failure. Louise Rodino-Klapac, Ph.D., chief scientific officer and head of research & development at Sarepta, said during the investor call this morning.

She said about 30% of patients who have received Elevidys experienced elevated liver enzymes within the first 90 days of treatment. These patients responded rapidly to an increase in steroids. But acute liver injury was not seen in previously treated patients.

“Ambulatory status is a surrogate for the severity of disease progression, and so we’ve only seen the signal in this non-ambulatory population,” she said. “That is something that we will continue to evaluate when looking at immunosuppression and the non-ambulatory population.”

Both deaths were of non-ambulatory patients who were participating in the phase 3 ENVISION trial of Elevidys, which was evaluating the gene therapy in older ambulatory and non-ambulatory individuals living with Duchenne muscular dystrophy. The most recent death was in a 15-year-old patient.

“We are currently evaluating this case in the context of this case alone and then in comparison to the previous case, but we haven’t identified a single risk factor,” Rodino-Klapac said. “We are working expeditiously to identify anything that we could potentially point to as a risk factor.”

Sarepta plans to propose to the FDA both a change to the label and an amendment to the ENVISION trial to add sirolimus to the regimen for non-ambulatory patients.

Preclinical data showed sirolimus significantly reduced liver enzyme elevations in non-human primates, indicating its potential to reduce liver-related safety events, Rodino-Klapac said. The data also show that sirolimus does not negatively impact gene expression in key tissues, supporting its use as a mitigation strategy.

Sarepta officials said during the investor call that this development doesn’t impact trials of separate gene therapies being studied to treat patients with limb-girdle muscular dystrophy. “The disease progression is different and unique in limb-girdle muscular dystrophy as compared with DMD; we have not seen a signal of acute liver failure in this population,” Rodino-Klapac.