FDA Delays Action on Stealth’s Barth Syndrome Therapy

Rare Daily Staff

The U.S. Food and Drug Administration notified Stealth Biotherapeutics that it would not meet today’s action date for the company’s new drug application for elamipretide, the company’s experimental therapy for the treatment of the ultra-rare mitochondrial disease Barth syndrome.

The agency has not yet set a new date for it to act on the Stealth application. More than 35 patients worldwide have received expanded or emergency access to elamipretide for the treatment of Barth syndrome, including many critically ill infants and toddlers affected by the disease. Stealth said it will continue supporting expanded and emergency access to elamipretide while advancing towards a potential FDA approval.

In January, the FDA notified Stealth that new analyses requested by the agency in late November and early December 2024 required a delay of the PDUFA date to April 29, 2025. The reason for the latest delay, though, is unclear, and that has led to some speculation in press accounts that it may be tied to staffing issues at the FDA in the wake of cuts.

Earlier this month, Biocentury reported that FDA sources said up to 25 percent of the agency’s reviewers—about 600 people—have recused themselves from active reviews as they pursue jobs in the private sector. Under FDA rules, employees are required to recuse themselves from agency decisions when pursuing outside employment.

As of deadline, the FDA did not respond to a Rare Daily email inquiry about the cause of the delay and whether staffing issues played a role.

Barth syndrome is an ultra-rare genetic mitochondrial disease leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age five. Barth syndrome occurs primarily in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are no approved therapies for the treatment of Barth syndrome.

Elamipretide is a peptide that targets the inner mitochondrial membrane where it binds to cardiolipin, which plays an essential role in energy conversion within cells. It has received Orphan Drug, Fast Track, Priority Review, and Rare Pediatric designations from the FDA and Orphan Drug designation from the European Medicines Agency for the treatment of Barth syndrome.

The delay is the latest setback in Stealth’s efforts to win approval for elamipretide. Stealth first submitted a new drug application to the FDA at the end of August 2021, despite the agency’s recommendation that additional controlled data be generated to support its review. The FDA refused to consider the application at that time, stating the drug had not been studied in enough patients and that the submission lacked an adequate and well-controlled trial. That’s even though the principal investigator of the Stealth study had said that she screened every patient in North America who fit the clinical trial’s inclusion criteria.

In March 2024, the FDA accepted the company’s application for elamipretide under standard review. In May 2024, it granted the company priority review for elamipretide. The agency’s willingness to accept the application came after the Barth Syndrome Foundation delivered a petition at the end of 2024 with nearly 20,000 signatures asking the agency to consider approving elamipretide. That was the most visible of a long list of efforts begun in 2019 by the company and the patient community to get the agency to advance elamipretide. This included letter writing campaigns, meetings between the FDA and Stealth, and nearly 200 meetings with legislators.

In October 2024, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10 to 6 that elamipretide is effective for treating patients with Barth syndrome.