The FDA has cast doubt on Stealth BioTherapeutics' application for elamipretide, an investigational peptide therapeutic intended to treat the ultra-rare Barth syndrome. In a briefing document released ahead of an advisory committee meeting, FDA reviewers stated they do not believe the available evidence sufficiently demonstrates elamipretide's effectiveness in treating Barth syndrome.
The primary concern stems from the Phase II TAZPOWER trial, a placebo-controlled, randomized, and double-blinded study. According to the FDA, elamipretide failed to meet its primary endpoints in the first part of the TAZPOWER trial, which assessed efficacy using the 6-minute walk test and total fatigue score. Stealth BioTherapeutics positioned this first part of TAZPOWER as the core of their evidence base.
To bolster their application, Stealth BioTherapeutics also submitted data from the open-label extension phase of TAZPOWER and a third, externally-controlled trial. However, the FDA deemed neither of these studies as adequate and well-controlled trials capable of independently establishing elamipretide's effectiveness.
Concerns Over Surrogate Biomarker
The FDA also indicated that elamipretide would likely not qualify for accelerated approval based on the proposed surrogate biomarker of left ventricle stroke volume (LVSV). The agency stated that cardiac hemodynamics and the cardiac effects on functional capacity are influenced by a complex interplay of physiological and neurohormonal factors, not LVSV alone.
Postmarketing Plans Deemed Inadequate
Furthermore, the FDA found Stealth BioTherapeutics' proposed postmarketing observational plan to be inadequate for confirming clinical benefit.
The Cardiovascular and Renal Drugs Advisory Committee is scheduled to convene to discuss whether Stealth BioTherapeutics' data package provides sufficient evidence of elamipretide's efficacy and whether accelerated approval is warranted.
About Barth Syndrome and Elamipretide
Barth syndrome is a rare genetic condition caused by a gene mutation affecting mitochondrial energy production, impacting multiple bodily systems, including muscles and the heart.
Elamipretide is an investigational peptide therapeutic designed to target the inner mitochondrial membrane and bind reversibly to cardiolipin, a phospholipid crucial for maintaining mitochondrial activity. Preclinical data suggest elamipretide improves mitochondrial respiration, boosts ATP production, and reduces the formation of potentially harmful chemicals.
