FDA Advisory Committee Backs First Drug for Barth Syndrome

Heartbreaking stories from patients, parents, and doctors of children afflicted with Barth syndrome, a rare and deadly condition, swayed an FDA advisory committee on Thursday. This emotional testimony is likely to lead to a challenging decision for regulators in the upcoming months. The FDA's Cardiovascular and Renal Drugs Advisory Committee voted 10-6 in favor of the effectiveness of Stealth BioTherapeutics’ drug elamipretide for treating the disease.

The vote came after the committee raised concerns about drawing conclusions from a natural history data-based trial and noted the variability of the effects observed in a small placebo-controlled trial. While some committee members viewed data from a walk test as a positive indicator from the drug’s pivotal trial, others questioned its reliability.

Panelist Carole Tucker from the University of Texas Medical Branch, who voted positively, mentioned that the outcomes without the drug were bleak, and just the hope provided by the drug might have influenced some individuals. She also expressed her anticipation for more postmarket data. The FDA’s final approval decision is expected by January 29, 2025.

Barth syndrome is an ultra-rare mitochondrial disease affecting only about 130 boys and young men in the US. It is marked by skeletal muscle weakness, delayed growth, fatigue, and heart muscle weakness. Currently, there are no approved treatments or other potential treatments nearing approval for this disease.

The FDA reviewers had numerous questions about whether elamipretide, previously rejected, could be deemed effective. They also questioned whether the 24-patient trial was sufficient to be considered a well-controlled trial adequate for approval. Stealth BioTherapeutics highlighted the drug’s safety and the comprehensive data from the placebo-controlled trial, supplemented by anecdotal results from an open-label extension.

In the double-blind, placebo-controlled trial, only 12 patients received the drug. The FDA reviewers informed the committee that the data did not show a statistically significant difference between elamipretide and placebo on primary or secondary endpoints. Nonetheless, 10 of the 12 patients from the initial trial continued into an open-label extension study, where the company reported they fared well. However, the FDA reviewers noted that only eight boys remained on treatment after 3.2 years, and merely three boys continued the drug until 3.7 years.

During the open public hearing, patients, parents, and doctors of children with Barth syndrome urged for the drug’s approval, citing improvements in weight gain and activities previously unachievable. The panelists discussed postmarketing and labeling questions with Peter Stein, Director of the FDA’s Office of New Drugs, and debated whether the data was sufficient for approval.

Despite the compelling anecdotal evidence presented, some committee members remained skeptical about the fundamentals of the elamipretide trial. Stealth BioTherapeutics’ CEO, Reenie McCarthy, expressed satisfaction with the advisory committee’s consideration of elamipretide’s data package. She emphasized the positive results from the natural history control trial, the durable open-label extension data, and expanded access cases, recognizing these data as supportive of elamipretide’s potential to improve the lives of patients suffering from this devastating disease.