Elamipretide is a first-in-class mitochondria-targeted agent by Stealth Biotherapeutics. In January 2025, its FDA review for the treatment of Barth syndrome was extended by three months. Barth syndrome is an ultra-rare metabolic and neuromuscular genetic disorder that primarily affects male individuals. Characteristic manifestations include cardiomyopathy, with onset usually before 5 years of age, as well as neutropenia, skeletal myopathy and growth delay. Elamipretide was evaluated in the single-site, blinded, placebo-controlled, crossover Phase 2/3 TAZPOWER trial in 12 ambulatory male subjects 12 years of age and older with confirmed Barth syndrome.³ Elamipretide was administered as a 40 mg subcutaneous injection once daily. While elamipretide did not result in significant improvements in the primary endpoint of 6-minute walk test (6MWT) or in secondary endpoints measuring fatigue scores or muscle strength compared with placebo at the 12 weeks, increasing and persistent improvements that reached statistical significance were observed across these domains during the open-label extension period. After 24 total weeks of drug exposure, the mean 6MWT improved by 16% (60.5 meters; p=0.02), fatigue scores decreased by 19% (p=0.03), and there was a 30% improvement in hand strength (measured by handheld dynamometry; p=0.003). Elamipretide was generally well-tolerated. The FDA granted elamipretide Fast Track, Orphan Drug and Rare Pediatric Disease designations and a Priority Review. In addition, the FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 10 to 6 in favor of the effectiveness of elamipretide for treating Barth syndrome. If approved, elamipretide will be the first treatment available to treat this ultra-rare condition.