The US Food and Drug Administration (FDA) has rejected Stealth BioTherapeutics’ elamipretide for the treatment of Barth syndrome after a lengthy review.
The complete response letter (CRL) issued by the FDA comes after a 16.5-month priority review cycle and despite a positive vote by an advisory committee (AdComm) meeting.
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It is not the end of the road for Stealth Bio’s elamipretide, however, with the biotech and the FDA identifying a potential accelerated approval path forward based on a new clinical endpoint.
To support a potential new drug application (NDA), Stealth Bio has cut 30% of its workforce to conserve resources. The company used to be publicly traded but went private in 2022. Its last publicly disclosed headcount stood at 38 in 2021.
The snub by the FDA caps off a tumultuous application process for Stealth Bio’s mitochondria-targeting peptide elamipretide. The Massachusetts-based biopharma first presented data to the FDA in 2019 as it eyed approval as a treatment for Barth syndrome, an ultra-rare genetic condition caused by a mutation on the X chromosome.
Later in 2021, the FDA advised that the company run another Phase III trial. Stealth Bio went ahead with the NDA filing anyway after a feasible trial design was not identified, though the FDA did not even accept the application.
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By GlobalDataA new NDA was submitted in January 2024, which the FDA did accept, and that was later converted into a priority review. An AdComm voted 10-6 in favour of Stealth Bio’s drug being an effective treatment of Barth syndrome, but the FDA delayed the Prescription Drug User Fee Act (PDUFA) action date by three months from January to April 2025.
This came amid an inspection by the FDA of a third-party manufacturing facility for elamipretide, though Stealth Bio asserts that no specific deficiencies were recorded. The agency then missed the revised deadline, delaying the application again. The CRL eventually followed on 29 May.
The path forward is positive for Stealth Bio, but still complex. The FDA has agreed to consider knee extensor muscle strength as a potential intermediate clinical endpoint to support accelerated approval. Stealth Bio had already included data on this in its NDA, showing an improvement of over 45% that lead to improvements in a six-minute walk test (6MWT). Stealth Bio and the FDA will meet in June 2025 to discuss the proposed post-marketing study.
“We recognise that the FDA’s recommendation for an accelerated approval for elamipretide in Barth syndrome offers a path forward for this incurable paediatric disease that affects an incredibly small number of individuals worldwide,” said Reenie McCarthy, Stealth Bio’s CEO.
“We hope the FDA will also prioritise ensuring rapid access for neonates affected by the disease subject to appropriate post-marketing safety monitoring,” McCarthy added.
Barth syndrome, which primarily affects boys due to its X chromosome mutation pathogenesis, causes heart problems, muscle weakness, and immune system issues. There are currently no FDA-approved therapy for the condition.
