FDA Rejects Stealth BioTherapeutics' Elamipretide for Barth Syndrome, Company Plans Resubmission

Stealth BioTherapeutics faced a setback as the U.S. Food and Drug Administration (FDA) rejected its application for elamipretide, a peptide targeting mitochondria, in the treatment of Barth syndrome. The Massachusetts-based biotech company, however, remains optimistic as the agency outlined a potential path to accelerated approval.

Rejection and Resubmission Strategy

The FDA's decision came after a prolonged 16.5-month priority review cycle, which included multiple delays. Despite the setback, Stealth BioTherapeutics emphasized that the FDA has agreed to consider knee extensor muscle strength as a potential intermediate clinical endpoint to support accelerated approval.

The company plans to resubmit its application using data from a phase 2 trial that reportedly showed a more than 45% improvement in extensor muscle strength with elamipretide treatment. To conserve cash for the resubmission process, Stealth has implemented a 30% reduction in its workforce.

Clinical Trial Data and FDA Concerns

The initial submission was based on a phase 2/3 trial that missed its primary endpoints, including the six-minute walk test. While Stealth reported statistically significant muscle changes from baseline, the FDA deemed the data "exploratory and uninterpretable."

Stealth maintains that extensor muscle strength significantly correlated with improvements on the six-minute walk test, despite the trial missing this endpoint. This discrepancy is likely to be a key point of discussion in the planned resubmission.

Regulatory Timeline and Advisory Committee Vote

Stealth's journey to bring elamipretide to market for Barth syndrome has been fraught with challenges:

• 2019: Initial data presentation to the FDA
• 2021: FDA advises additional phase 3 trial; Stealth submits application without extra data
• March 2024: FDA accepts resubmitted application for standard review
• May 2024: Priority review designation granted
• October 2024: Advisory committee votes 10-6 in favor of the filing
• January 2025: Original target decision date missed
• May 2025: FDA issues complete response letter

The extended review process and multiple delays highlight the complexities involved in bringing treatments for ultra-rare diseases to market.