FDA Restricts Sarepta's Duchenne Gene Therapy Elevidys, Adds Boxed Warning

The U.S. Food and Drug Administration (FDA) has imposed significant restrictions on Sarepta Therapeutics' gene therapy Elevidys for Duchenne muscular dystrophy (DMD), following reports of patient deaths linked to liver toxicity. The regulatory action includes the addition of a boxed warning and narrowing of the patient population eligible for treatment.

Label Changes and Safety Warnings

The FDA's decision to update Elevidys' label comes in response to serious safety concerns. The new boxed warning, the agency's most severe safety signal, alerts patients and healthcare providers to the risk of severe liver injury and acute liver failure, which can potentially lead to death.

The updated label also includes a "limitation of use" clause, recommending against Elevidys treatment for patients with preexisting liver impairment, recent vaccinations, or recent/active infections within the past four weeks.

Additionally, the FDA has narrowed the indicated patient population for Elevidys. The gene therapy is now restricted to ambulatory DMD patients aged 4 years and older with a confirmed mutation in the DMD gene. This change effectively removes the option for non-ambulatory patients to receive the treatment, a decision prompted by the reported fatalities.

Post-Marketing Study and Enhanced Monitoring

As part of the label update, Sarepta is required to conduct a post-marketing observational study involving approximately 200 patients. This study aims to further assess the risk of serious liver injury associated with Elevidys treatment. Patients will undergo periodic liver function tests for at least 12 months following gene therapy administration.

The new label maintains the requirement for weekly liver function monitoring for a minimum of three months post-treatment. It also introduces a new recommendation for patients to remain near an appropriate medical facility for at least two months after infusion, as liver injuries typically manifest within this timeframe.

Industry Impact and Company Response

The labeling changes come after a tumultuous period for Sarepta, which saw the voluntary suspension of Elevidys administration to non-ambulatory patients earlier this year. The company and its ex-U.S. partner Roche took this action following reports of two patient deaths due to acute liver failure.

Despite the restrictions, Sarepta's stock price saw a 7% increase following the announcement, suggesting that investors view the FDA's decision as a balanced approach that allows continued marketing of Elevidys while addressing safety concerns.

Sarepta has indicated plans to commence a study on an enhanced sirolimus immunosuppressive regimen to address the risk of acute liver failure and injury. The company aims to potentially resume dosing for non-ambulatory patients, pending FDA agreement.

The developments surrounding Elevidys have broader implications for the gene therapy field, particularly for treatments using adeno-associated virus vectors. The FDA's actions highlight the ongoing challenges in balancing the potential benefits of innovative therapies with patient safety concerns in the rapidly evolving landscape of genetic medicine.