Stealth BioTherapeutics’ 16.5-month priority review cycle has ended in rejection. After delays, Stealth said the FDA turned down its request but set out a path to accelerated approval, leading the biotech to lay off 30% of its staff to conserve cash for a resubmission.
Massachusetts-based Stealth applied for approval of elamipretide, a peptide that targets mitochondria, in the ultra-rare genetic condition Barth syndrome on the strength of a phase 2/3 trial that missed its primary endpoints. An advisory committee voted in favor of the filing in a split decision but, after twice delaying its ruling, the FDA has issued a complete response letter.
Stealth emphasized the positives. The FDA has agreed to consider knee extensor muscle strength as a potential intermediate clinical endpoint to support accelerated approval, the biotech said. Stealth plans to resubmit for accelerated approval using data from a phase 2 trial that it said showed extensor muscle strength improved by more than 45% on elamipretide.
Barth syndrome almost always affects boys and is a metabolic disorder that affects the heart, muscles, immune system, as well as overall growth. It can dramatically reduce life expectancy, with mortality linked to heart failure.
The biotech included muscle strength data in the recently rejected submission. While Stealth said muscle changes from baseline were statistically significant, the FDA called (PDF) the biotech’s data “exploratory and uninterpretable.” Stealth said Thursday that extensor muscle strength significantly correlated with improvements on the six-minute walk test. The trial missed its six-minute walk test endpoint.
The FDA and Stealth look set to relitigate the debate, with the biotech planning to file for approval once again. Stealth has laid off 30% of its staff to free up funds for the resubmission. The biotech went private in 2022, freezing its publicly disclosed headcount at 38 as of the end of 2021.
Stealth’s bid to bring elamipretide to market in Barth syndrome had already turned into a saga before the latest twist. The biotech first presented data to the FDA in 2019. Two years later, the agency advised Stealth to run another phase 3 trial before seeking approval. Stealth submitted an application without the extra phase 3 data and soon received a refusal-to-file letter from the FDA.
In March 2024, the FDA accepted Stealth’s resubmitted approval request for standard review. The FDA granted priority review designation to the filing two months later but kept its original target decision of January 2025. An advisory committee gave Stealth a boost by voting 10-6 in favor of the filing in October. Yet, the FDA delayed its decision by three months—and then missed its revised deadline.
Had the FDA granted priority review status when it accepted the filing, rather than two months later, the PDUFA date would have been late September 2024. Stealth finally received a decision eight months after that theoretical PDUFA date. The biotech said the entire cycle took 16.5 months.