FDA Decision Looms for Stealth BioTherapeutics' Elamipretide in Ultra-Rare Barth Syndrome

The pharmaceutical industry holds its breath as the U.S. Food and Drug Administration (FDA) approaches a critical decision on Stealth BioTherapeutics' elamipretide, a potential first-ever treatment for Barth syndrome. With the target review date set for September 26, 2025, the outcome could mark a significant milestone for both the biotech company and the small community of patients affected by this ultra-rare mitochondrial disease.

A Decade-Long Journey Nears Its Climax

Stealth BioTherapeutics' pursuit of a treatment for Barth syndrome began in 2014 when the Barth Syndrome Foundation approached the company at a conference. The foundation recognized the potential match between elamipretide's mechanism of action and the primary defect in Barth syndrome, initiating a collaboration that has spanned nearly a decade.

The road to potential approval has been fraught with challenges. In January 2024, Stealth submitted elamipretide for traditional approval, only to face rejection in May of the same year. This setback forced the company to reduce its workforce by 30% to support a new drug application (NDA) resubmission.

On August 15, 2025, Stealth filed a resubmission for accelerated approval, as recommended by the FDA. The agency accepted the application less than a week later, setting an unusually rapid target review date of September 26, 2025.

The Case for Elamipretide and FDA's New Approach to Ultra-Rare Diseases

Barth syndrome, affecting only 150 people in the United States, exemplifies the challenges of developing treatments for ultra-rare diseases. The FDA's recent unveiling of the Rare Disease Evidence Principles framework aims to streamline the approval process for such conditions.

Elamipretide targets mitochondria, which generate approximately 90% of the energy needed for healthy organ function. The drug interacts with a key mitochondrial phospholipid to improve structure and function in dysfunctional mitochondria.

Despite mixed results in clinical trials, including a failure to meet primary endpoints in the first part of the Phase II TAZPOWER trial, Stealth has proposed accelerated approval based on an intermediate endpoint of knee extensor muscle strength. This measure improved by around 45% in the open-label study and correlated with improvements in the six-minute walk test.

Community Support and Clinical Impact

The Barth syndrome community has rallied behind elamipretide, with patients and families reporting significant improvements in quality of life. Kate McCurdy, board chair at the Barth Syndrome Foundation, described visible benefits: "We can see kids walk upstairs when they could never do that before. We've seen them be able to go to school for a full day when they could never do that before."

A petition signed by 82 Barth syndrome experts calling for elamipretide's approval was submitted to FDA Commissioner Marty Makary on August 8, 2025. The petition included an addendum from an advisory committee member who initially voted against the drug but has since changed their position after witnessing its effects.

As of April 30, 2025, 35 patients worldwide had received elamipretide under expanded or emergency access programs, including critically ill infants and toddlers. McCurdy emphasized the drug's potential life-saving impact on younger patients and its life-enhancing effects for older individuals.

However, securing approval for younger children presents a challenge, as the Phase II TAZPOWER trial only studied elamipretide in patients 12 years and older. The FDA's complete rejection letter indicated difficulties in extrapolating efficacy findings to younger patients with life-threatening heart failure.

As the pharmaceutical industry awaits the FDA's decision, the outcome will not only determine the fate of elamipretide but also potentially set a precedent for the approval process of treatments for ultra-rare diseases.