Sarepta voluntarily halts Elevidys shipments in US after FDA request
Move follows patient death in clinical trial of another MD gene therapy
Sarepta Therapeutics is voluntarily halting all shipments of Elevidys (delandistrogene moxeparvovec-rokl) in the U.S. after a request from the U.S. Food and Drug Administration (FDA).
The company had initially refused to pause the shipments of its gene therapy for Duchenne muscular dystrophy (DMD) for individuals with DMD who are able to walk, but has since agreed.
These updates follow the death of a man who died in a clinical trial testing a different gene therapy being developed by Sarepta, as well as two deaths of patients treated with Elevidys earlier this year. The FDA says it now has substantial safety concerns related to some of the molecular technology used in these gene therapies.
Sarepta initially insisted that there are no new safety concerns for Elevidys in people with DMD who can walk, but the company announced on Monday that it would pause all shipments to allow it time to work with the FDA to address the situation. The prescribing information for Elevidys is now expected to be updated to reflect the new safety concerns.
“As a patient-centric organization, the decision to voluntarily and temporarily pause shipments of Elevidys was a painful one, as individuals with Duchenne are losing muscle daily and in need of disease-modifying options,” Doug Ingram, CEO of Sarepta, said in a company press release. “It is important for the patients we serve that Sarepta maintains a productive and positive working relationship with FDA, and it became obvious that maintaining that productive working relationship required this temporary suspension while we address any questions that FDA may have and complete the Elevidys label supplement process.”
Elevidys is a gene therapy designed to deliver to muscle cells a gene encoding micro-dystrophin — a shortened but functional version of the protein that is defective in DMD. The therapy delivers its genetic payload using a viral vector, which is basically a virus that’s been engineered so it won’t cause infections. The viral vector used in Elevidys is called AAVrh74, which has a high affinity for muscle tissue.
The FDA last year granted Elevidys traditional approval for people with DMD ages 4 and older who can walk, based on clinical trial data indicating that the therapy improves measures of motor function. At the same time, the FDA granted accelerated approval — a form of conditional approval — to Elevidys for use in nonambulatory DMD patients ages 4 and older.
No fatalities reported in clinical trials testing Elevidys
No fatal reactions to Elevidys had been reported in clinical trials, but in March, a nonambulatory teenager with DMD died of acute liver injury after treatment with the gene therapy. A second death from acute liver injury following Elevidys treatment in a nonambulatory DMD patient was reported in June. At that time, Sarepta announced it would be halting all shipments of Elevidys for nonambulatory patients, but would continue shipments for patients who can walk.
Last week, Sarepta announced the death of a nonambulatory patient in a clinical trial testing SRP-9004, its gene therapy candidate for limb-girdle muscular dystrophy (LGMD) type 2D. Sarepta reported this death to the FDA in accordance with applicable law, the company stated.
Sarepta has noted that SRP-9004 and Elevidys are distinct gene therapies for different diseases, given at a disparate doses and manufactured using different processes. The FDA’s concern, however, is that SRP-9004, Elevidys, and other investigational therapies in Sarepta’s pipeline all use the same AAVrh74 viral vector. Immune reactions against a viral vector are thought to be a major reason that gene therapies can cause liver damage when administered into the bloodstream.
Following the three deaths, the FDA announced on Friday it was putting Sarepta’s gene therapy clinical trials for LGMD on hold. The agency also asked Sarepta to stop all shipments of Elevidys, and it revoked a platform technology designation that had been given to the AAVrh74 vector.
There is no new or changed safety information for the ambulant patient population. … [Sarepta’s goal] is to preserve access to Elevidys so that patients, their families, and their doctors can have well informed discussions and make their own choice about treatment.
“Today, we’ve shown that this FDA takes swift action when patient safety is at risk,” Marty Makary, MD, the FDA commissioner, said in an agency press release. “We believe in access to drugs for unmet medical needs but are not afraid to take immediate action when a serious safety signal emerges.”
Sarepta initially pushed back, saying there is no reason to stop shipments of Elevidys for ambulatory patients.
“There is no new or changed safety information for the ambulant patient population,” Wendy Erler, senior vice president of patient affairs at Sarepta, wrote in a letter to the community published Saturday. At the time, Erler wrote that Sarepta’s goal “is to preserve access to Elevidys so that patients, their families, and their doctors can have well informed discussions and make their own choice about treatment.”
But by late Monday, Sarepta announced it would pause Elevidys shipments effective by close of business today to allow time to update the gene therapy’s label and respond to any FDA requests for information. The company said it “looks forward to a collaborative, science-driven review process and dialogue with the FDA.”
Sarepta agrees to new black box warning on treatment label
Sarepta and the FDA have already aligned on a decision to add a black box warning to the prescribing information for Elevidys. That warning will note that the gene therapy can cause acute liver injury and acute liver failure.
The FDA has also asked Sarepta to narrow the therapy’s indication to only ambulatory patients — which would effectively revoke the conditional approval for nonambulatory patients.
Sarepta didn’t directly address this request in its statements, but did emphasize that it was assembling an expert committee to consider an enhanced immunosuppression regimen for Elevidys in nonambulatory DMD patients. The company said it would share recommendations with the FDA and will continue to dialogue with the agency.
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