Although the FDA has rejected Stealth’s new drug application for Barth syndrome candidate elamipretide, the agency identified a potential accelerated approval pathway. The company has pared down its staff to conserve resources to fund a potential resubmission.
To help direct resources toward a potential new drug application resubmission for Barth syndrome therapy elamipretide, Stealth BioTherapeutics has laid off 30% of its workforce, the company announced May 29. The Needham, Massachusetts–based biotech did not specify how many employees it let go, but its LinkedIn People page lists 65 associated members, meaning the cuts may have affected around 28 staffers.
Stealth, which is working on therapies for diseases involving mitochondrial dysfunction, submitted its new drug application for elamipretide in January 2024. Although the FDA has now rejected it, the company shared in its announcement that the agency identified a potential accelerated approval pathway that requires NDA resubmission. Stealth noted that the move follows years of discussions with the FDA and a 2024 Cardiovascular and Renal Drugs Advisory Committee meeting that concluded the drug candidate is effective for treating Barth syndrome. The rare condition is typically characterized by an enlarged and weakened heart, muscle weakness and recurrent infections, among other symptoms.
In October, the committee voted 10-6 in favor of elamipretide. However, many members noted the flawed nature of Stealth’s data supporting the drug and uncertainties regarding its clinical efficacy.
In its announcement, Stealth noted that elamipretide’s development path has been complex, involving four different FDA review divisions since the company first presented data to the FDA in 2019.
“The ultra-rare nature of Barth syndrome, the FDA’s reservations regarding the positive data from SPIBA-001, a Phase 3 natural history control study assessing the functional endpoints utilized in the TAZPOWER open-label extension, and the FDA’s prior refusal to consider an accelerated approval pathway all contributed to the challenges of the review,” the biotech noted in the announcement.
The complex process also includes a missed prescription drug user fee act (PDUFA) date. On April 29, Stealth announced that the FDA had failed to meet that day’s target decision date for elamipretide. According to the biotech, the agency informed the company of the delay on the day that review was due.
Regarding an NDA resubmission, Stealth noted in its May 29 announcement that the FDA has agreed to consider knee extensor muscle strength as a potential intermediate clinical endpoint to support accelerated approval. In its January 2024 NDA, the company included data showing that knee extensor muscle strength, which improved by over 45% in a Phase II clinical trial, was significantly correlated with improvements on a six-minute walk test.
In the company’s press release, Stealth CEO Reenie McCarthy said, “We hope the FDA will also prioritize ensuring rapid access for neonates affected by the disease subject to appropriate post-marketing safety monitoring. We are experiencing a sharp increase in emergency access requests for critically ill infants from medical experts worldwide following the recent publication of several positive case study reports.”
