Elevidys shipments for ambulatory DMD patients to resume
Sarepta agreed to halt shipments at request of FDA following patient deaths
Sarepta Therapeutics will soon resume shipping Elevidys (delandistrogene moxeparvovec-rokl) for ambulatory Duchenne muscular dystrophy (DMD) patients, following a review of safety data by the U.S. Food and Drug Administration (FDA), which recommended the voluntary pause on the gene therapy end.
“Last week, at the suggestion of FDA, Sarepta made the difficult decision to pause shipments of Elevidys to provide the FDA with an opportunity to complete a review of available safety information,” Doug Ingram, Sarepta’s CEO, said in a press release. “We are very pleased that FDA chose to rapidly and comprehensively complete that review, and to recommend that we remove our voluntary pause and resume shipment of Elevidys for ambulatory patients. The FDA’s swift review evinces a commitment to the Duchenne population, a commitment shared by Sarepta.”
DMD is caused by mutations in the gene that encodes dystrophin, a protein needed to maintain muscle health. Elevidys is a one-time therapy that delivers a gene that encodes a shortened, but functional version of dystrophin to muscle cells. In the U.S., Elevidys is approved for patients 4 and older who can walk and is conditionally authorized for those 4 and older who cannot walk.
Placing a hold on shipments
Earlier this year, Sarepta announced that two nonambulatory DMD patients had died of acute liver failure after treatment with Elevidys. After the second death, Sarepta stopped shipments of Elevidys for nonambulatory patients.
This month, a third nonambulatory patient died in a trial testing SRP-9004, Sarepta’s investigational gene therapy for limb-girdle muscular dystrophy (LGMD) type 2D. Although this death was related to a different therapy, the FDA flagged safety concerns because SRP-9004 and Elevidys both use the same viral vector to deliver genes to muscle cells, and immune reactions to the viral vector are thought to underlie liver damage that occurs as a side effect of gene therapy.
With an average life expectancy of only 28 years, achieving disease stabilization is a major advance for individuals living with Duchenne, their families and caregivers. We are confident in the value Elevidys can bring to ambulatory patients.
After the third death, the FDA asked Sarepta to voluntarily halt all shipments of Elevidys. The company agreed after initially resisting.
Last week, the FDA announced it was investigating the death of an 8-year-old boy with DMD in Brazil who died after receiving Elevidys. Sarepta said the death wasn’t related to Elevidys after Brazil’s health regulatory agency stated it was likely caused by a serious viral infection made worse from immune system suppression. The FDA concluded the boy’s death was indeed “unrelated to the gene therapy product itself.”
In a letter to the DMD community, Wendy Erler, senior vice president of patient affairs at Sarepta, said the company will soon be contacting treatment centers.
“Sarepta’s team will be reaching out to sites of care that had infusions scheduled for July and August to inform them of the availability of Elevidys for ambulatory patients, encourage them to have conversations with patients and families about the risks and benefits of treatment, and allow them to make informed decisions about their care,” Erler said.
Seeking approvals
Sarepta still maintains a hold on shipments of Elevidys for nonambulatory patients. The company is working with the FDA to update Elevidys’ prescribing information.
“We look forward to working collaboratively with the FDA to complete the safety label update for Elevidys and to discussing the approach to risk-mitigation for nonambulatory patients, who remain on pause pending the outcome of those discussions,” Ingram said.
As Sarepta works to resume shipments for ambulatory DMD patients in the U.S., efforts are underway to seek approval of the gene therapy in other countries. Those efforts hit a stumbling block in Europe last week when a committee of the European Medicines Agency (EMA) recommended against conditionally authorizing Elevidys for ambulatory DMD patients.
Recommendations from the Committee for Medicinal Products for Human Use (CHMP) are reviewed by the European Commission, which has final say over approvals in the European Union. Roche, which holds the rights to Elevidys outside the U.S., said it plans to discuss possible next steps with the EMA.
“We are disappointed by the CHMP’s negative opinion, given the urgent need for disease-modifying therapies for children in the EU living with Duchenne,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release. “With an average life expectancy of only 28 years, achieving disease stabilization is a major advance for individuals living with Duchenne, their families and caregivers. We are confident in the value Elevidys can bring to ambulatory patients.”
A Phase 3 trial called EMBARK (NCT05096221) tested Elevidys against a placebo in more than 120 boys with DMD, ages 4 to 7. The study missed its main goal, which was to show how treatment affected scores on the North Star Ambulatory Assessment (NSAA), a measure of motor function. Significant gains were seen in other measures, however, such as the time to walk 10 meters (nearly 33 feet) and the time to stand up from lying down.
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