Stealth Resubmits Application to FDA for Approval of Barth Syndrome Drug

Rare Daily Staff

Stealth BioTherapeutics said it resubmitted its application to the U.S. Food and Drug Administration for approval to market elamipretide, its experimental therapy for the rare mitochondrial disease Barth syndrome.

Barth syndrome is an ultra-rare genetic mitochondrial disease that leads to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85 percent of early deaths occurring by age 5.

Elamipretide is a peptide that targets the inner mitochondrial membrane, where it binds to cardiolipin, which plays an essential role in energy conversion within cells.

The FDA in May 2025 told the company it would not approve its application in its current form, and recommended that it resubmit for accelerated approval based on improvements in knee extensor muscle strength, an intermediate clinical endpoint. Knee extensor muscle strength improved by more than 45 percent in the TAZPOWER phase 2 open-label clinical trial, and was significantly correlated with gains in the six-minute walk test, an FDA-recognized indicator of clinical benefit.

The complete response also cited current good manufacturing practice (CGMP) observations from a May 2025 surveillance inspection of a third-party manufacturing facility. In July 2025, the FDA confirmed that the facility remains in full CGMP compliance, with no corrective action required, and advised Stealth to include this confirmation in its resubmission, which now also incorporates the agreed-upon phase 4 protocol, previous feasibility data, and proposed timelines.

FDA policy is to classify resubmissions as Class 1 (two-month review) or Class 2 (six-month review) upon receipt and preliminary review. Stealth said that the FDA signaled a likely Class 2 review, but the company has requested Class 1 because, with manufacturing concerns resolved, no new inspection should be required.

This is the third NDA submission containing the TAZPOWER muscle strength data, and comes 19 months after the prior priority review NDA submission.

If approved, this would be the first marketing authorization for elamipretide. Elamipretide is also in development for primary mitochondrial myopathy, and dry age-related macular degeneration.

“We appreciate FDA’s recent recognition of the seriousness of Barth syndrome, and the unmet need for potential therapies, and its commitment to complete its review of our NDA resubmission as expeditiously as possible,” said Reenie McCarthy, CEO of Stealth. “With FDA’s confirmation that the manufacturing observations cited in the [complete response] have been resolved, and the progress we have made to align on post-marketing trial design, we believe that all concerns raised by the FDA have been addressed.”

Photo: Reenie McCarthy, CEO of Stealth BioTherapeutics