Elamipretide: The first cardiolipin-directed mitochondrial therapeutic for Barth syndrome approved under accelerated...

Barth syndrome (BTHS) is a rare X-linked mitochondrial disorder caused by tafazzin mutations that impair cardiolipin remodeling, leading to mitochondrial dysfunction and symptoms such as cardiomyopathy, myopathy, and neutropenia. On September 19, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to elamipretide, the first therapy directly targeting the mitochondrial etiology of BTHS. Elamipretide binds to cardiolipin on the inner mitochondrial membrane, stabilizing respiratory chain supercomplexes, enhancing electron transport efficiency, and reducing reactive oxygen species production. In a randomized, double-blind, placebo-controlled, crossover trial, elamipretide resulted in no significant improvement in the 6-minute walk test or fatigue scores; however, sustained benefits were observed during a 168-week open-label extension. The most common adverse events were mild injection-site reactions. As a condition of accelerated approval, a confirmatory trial is required. Elamipretide represents a promising therapy addressing an unmet medical need in BTHS and provides a foundation for future mitochondria-targeted treatments.