FDA Misses Review Decision on Stealth Bio NDA
FDA says it will miss a 4/29 user fee review action extension on a Stealth BioTherapeutics NDA for elamipretide, a first-in-class mitochondria-targeted therapeutic for treating Barth syndrome. The review was extended in January to allow FDA to review supplemental information provided in response to recent requests that were received following the agency’s Cardiovascular and Renal Drugs Advisory Committee 10/10/2024 meeting, which voted 10 to 6 for approval.
“We appreciate the diligent efforts of the FDA to progress its review of our new drug application, including its confirmation of post-marketing requirements and its recent initiation of labeling discussions,” the company says. “We hope to gain more information on the revised action date in the coming days to inform our ability to continue supporting expanded and emergency access to elamipretide while advancing towards a potential FDA approval.”
An FDA advisory committee briefing document had reviewers questioning the company’s claim that elamipretide reduces pathological apoptosis/necrosis because it was not evaluated in cells from Barth subjects or in TAZ-deficient mice, the most relevant model of the disease. “Furthermore, no convincing data were provided that demonstrate any improvement of cardiac structure and function in TAZ-deficient mice over a treatment duration that did improve these measures in non-BTHS [Barth syndrome] disease models,” they wrote.
The review conundrum is presumably based on the challenges developers face when seeking to advance a product for an ultra-rare disease like Barth syndrome, which is known to affect less than 150 individuals in the U.S. and less than 300 individuals worldwide. Stealth and the agency have previously discussed the challenges of conducting additional clinical trials in Barth syndrome, especially in 2021 when the agency issued a refuse-to-file letter indicating that the application did not contain a single adequate and well-controlled trial that could establish evidence of effectiveness, according to the briefing document. FDA continued to recommend a new Phase 3 trial, but Stealth told FDA that their intent was to resubmit the NDA without conducting a new trial.
Stealth resubmitted the NDA 1/2024 and FDA says it decided to accept the elamipretide submission “so that it could undergo a more detailed review and be brought to an advisory committee for external input.” The submission is based on data from the SPIBA-001 Phase 3 Natural History Control Study and additional supporting efficacy and safety data from the TAZPOWER Part 2 baseline-controlled trial, according to the company. FDA previously granted elamipretide a fast track designation in 2017, orphan drug designation in 2018 and rare pediatric disease designation in 2020.