Elamipretide to treat Barth syndrome sees FDA target action delay | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

This week, Stealth BioTherapeutics Inc. announced that the FDA did not meet the April 29, 2025, Prescription Drug User Fee Action (PDUFA) date for elamipretide's new drug application (NDA) to treat Barth syndrome.¹

According to a press release from Stealth, the NDA was submitted to the FDA on January 29, 2024, with an initial PDUFA date of January 29, 2025. Following a new analyses request from the FDA in late November and early December of 2024, a delay in the target action date was announced, leading to a new PDUFA date of April 29, 2025.^1,2

"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," said Reenie McCarthy, CEO of Stealth, in a statement. "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."¹

Barth syndrome, elamipretide FDA advisory committee recommendation

Barth syndrome is an ultra-rare genetic mitochondrial disease that leads to exercise intolerance, debilitating fatigue, muscle weakness, recurrent infections, heart failure, and delayed growth, according to Stealth. With an associated reduced life-expectancy—85% of early deaths occur by age 5—Barth syndrome occurs primarily in males. The disease is estimated to impact 1 in 1,000,000 males worldwide, and approximately 150 individuals in the United States. As of April 30, 2025, there are no approved therapies to treat Barth syndrome.

In October of 2024, the FDA's Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 10-to-6 in favor of elamipretide's NDA. According to a press release at the time, the RDAC discussed the benefits and risks of elamipretide for the treatment of Barth syndrome, including results from the TAZPOWER Part 2 baseline-controlled extension study, the SPIBA-001 Phase 3 natural history control study, and additional supportive biomarker and preclinical data. The recommendation plays a role within the FDA, as it determines its decision regarding the potential approval of elamipretide.³

SPIBA-001 and TAZPOWER trial

In 2020, Stealth BioTherapeutics announced positive findings from its retrospective SPIBA-001 natural history study, which compared subcutaneous elamipretide treatment to a matched control group in patients with Barth syndrome. Among participants who received elamipretide for up to 1 year during the TAZPOWER trial and its open-label extension, the mean improvement on a 6-minute walk test (6MWT)—the study’s primary endpoint—exceeded 80 meters, versus less than 1 meter in the matched control group (P = .0005). Statistically significant gains were also observed in key secondary measures, including muscle strength and sit-to-stand performance.⁴

References:

1. Stealth Biotherapeutics announces delay in FDA action date for Barth syndrome application. StealthBioTherapeutics. Press release. April 29, 2025. Accessed April 30, 2025. https://stealthbt.com/stealth-biotherapeutics-announces-delay-in-fda-action-date-for-barth-syndrome-application

2. Stealth Biotherapeutics announces PDUFA action date extension for elaminpretide to treat patients with Barth syndrome. January 23, 2025. Accessed April 30, 2025. https://stealthbt.com/stealth-biotherapeutics-announces-pdufa-action-date-extension-for-elamipretide-to-treat-patients-with-barth-syndrome

3. Stealth Biotherapeutics announces positive vote from FDA Advisory Committee Meeting supporting potential approval of elamipretide for the treatment of Barth syndrome.

4. Stealth BioTherapeutics. Stealth Biotherapeutics announces positive results from study to evaluate efficacy of elamipretide in Barth patients compared to natural history control. Press release. BioSpace. February 18, 2020. Accessed April 30, 2025. https://www.biospace.com/stealth-biotherapeutics-announces-positive-results-from-study-to-evaluate-efficacy-of-elamipretide-in-barth-patients-compared-to-natural-history-control