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# FDA Questions Data in Stealth NDA for Barth Syndrome
- URL: https://www.fdaweb.com/fda-questions-data-in-stealth-nda-for-barth-syndrome/
- Published: 2024-10-08T12:00:00.000Z
- Updated: 2026-09-14T14:43:25.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5157938

FDA reviewers are questioning whether a Stealth BioTherapeutics NDA for elamipretide, a mitochondria-targeted therapy for treating Barth syndrome, contains adequate data to support approval. The ultra-rare genetic disease, which affects fewer than 130 individuals in the U.S., mostly occurs in males and is characterized by cardiac abnormalities often leading to heart failure and reduced life expectancy, recurrent infections, muscle weakness and delayed growth.

In an FDA [briefing document](https://www.fda.gov/media/182553/download?ref=fdaweb.com) released before a 10/10 advisory committee meeting, the reviewers say the company’s claim that elamipretide reduces pathological apoptosis/necrosis 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 write.

“Thus, while elamipretide improved mitochondrial bioenergetics in both BTHS and non-BTHS models, reductions in apoptosis/necrosis and related sequelae were observed only in models that differ in etiology from BTHS,” the reviewers continue. “Whether elamipretide might reduce apoptosis/necrosis and improve cardiac structure and function in BTHS models remains uncertain.”

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 in January 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.