The FDA has officially limited the label of Sarepta Therapeutics’ Elevidys, putting an end to a whirlwind few months that saw the abrupt departure—and reinstatement—of top agency official Vinay Prasad, M.D.
Duchenne muscular dystrophy (DMD) patients who are no longer able to walk independently can no longer receive the one-time gene therapy, the FDA said Friday. In addition, the drug’s indication now only covers ambulatory DMD patients who are at least 4 years of age.
The official label restriction comes five months after Sarepta and its ex-U.S. partner Roche voluntarily suspended giving Elevidys to non-ambulatory patients following the report of a second recipient who died after developing acute liver failure.
The updated label now includes a new boxed warning, the FDA’s most serious safety warning, describing the potentially deadly risks of serious liver injury and acute liver failure.
The changes don't come as a surprise after Sarepta shared its expected next steps for the gene therapy during the company’s third-quarter earnings report earlier this month. The company’s stock price was up about 7% Friday as of publication time.
In another Elevidys label tweak, the FDA now says the gene therapy "is not recommended in patients with preexisting liver impairment, recent vaccinations, or recent/active infections.” In this context, "recent" is defined as within four weeks, according to Sarepta.
This is a new “limitation of use” for the drug. Elevidys' previous label stated that treatment with the gene therapy “should be carefully considered in patients with preexisting liver impairment or chronic hepatic viral infection.”
The new label maintains a requirement for weekly liver function monitoring for at least three months after treatment. But it includes a new request that patients stay near “an appropriate medical facility” for at least two months post-infusion, according to the FDA.
Liver injuries after treatment with Elevidys are typically seen within the first two months, according to the drug's label. The two liver toxicity-related deaths were recorded within two months of Elevidys infusion.
In its Nov. 14 announcement, the FDA mentioned an additional serious but nonfatal case of acute liver injury, which involved several complications from other disorders.
The FDA is also requiring Sarepta to conduct a post-marketing observational study to further assess the risk of serious liver injury. The study will enroll about 200 DMD patients, who will be followed for at least 12 months after their Elevidys treatment, according to the agency.
The label update is the result of some back-and-forth between Sarepta and the FDA. The agency had briefly forced the biotech to pause all shipments of Elevidys but backed down to allow continued delivery to ambulatory patients late July.
Over the summer, Prasad, who leads the Center for Biologics Evaluation and Research overseeing gene therapies, was pushed out of the agency amid an aggressive campaign from DMD patient advocates. He was quickly hired back to the same position.
Besides the post-Elevidys patient deaths, another patient passed away after receiving Sarepta’s investigational candidate for limb-girdle muscular dystrophy. After that development, the FDA in July revoked the first-of-its-kind platform technology designation previously granted to the company’s AAVrh74 adeno-associated virus vector.
Despite the new label restriction, Sarepta has also floated the idea of an additional prophylactic immunosuppression measure to reduce the risk of liver toxicity.
Sarepta “expects to quickly commence a study of an enhanced sirolimus immunosuppressive regimen” to address the risk of acute liver failure and livery injury risk in order to potentially resume dosing for non-ambulatory patients, upon agreement with the FDA, the company said in a Nov. 14 release.