Despite substantial variability in the presented data and no well-controlled trial, the FDA advisory committee voted in favor of Stealth BioTherapeutics’ Barth syndrome therapy elamipretide, citing the urgent unmet need.
The FDA’s Cardiovascular and Renal Drugs Advisory Committee on Thursday threw its support behind Stealth BioTherapeutics’ peptide drug elamipretide for the treatment of the ultrare genetic disease Barth syndrome.
In a 10–6 vote, the panel of external experts found that elamipretide is an effective treatment for Barth syndrome—though this verdict was hardly unequivocal. Many of the committee members, even those who voted affirmatively, flagged the flawed nature of Stealth’s data supporting elamipretide and uncertainties regarding the drug’s clinical efficacy.
Still, most of the panelists recognized the practical difficulties of conducting trials in rare diseases and noted the urgent and major need for a treatment in Barth syndrome.
“This was just impossible,” Gerard Berry, professor of Pediatrics at Harvard Medical School, said during the meeting. “As a pediatrician and metabolic specialist who’s cared for these patients, to deprive somebody of being able to get the medicine that might help is just untenable for me.” Berry voted in favor of elamipretide.
“I don’t know if the case was made for me that there was an [adequate and well-controlled trial],” said Carole Tucker, chair of the Department of Physical Therapy and Rehabilitation Sciences at the University of Texas Medical Branch. “I don’t think the sponsor has necessarily provided that level of evidence.”
However, the data available showed a “trend toward the positive,” she continued. Combined with anecdotal evidence from patients who spoke at the committee meeting, this strengthened elampiretide’s case for her. Tucker voted yes.
“I felt like the most compelling thing that we heard was from the people who spoke in the open public hearing and it’s hard to know what to do with that,” Susan Ellenberg, professor emerita of Biostatistics, Medical Ethics and Health Policy at the Perelman School of Medicine in Pennsylvania. Ellenberg, who voted no, explained that in many cases, patients who receive experimental treatments experience improvements but still the therapies fail to delivery significant results in randomized trials.
“I don’t know how much regulatory flexibility the FDA is prepared to implement here,” Ellenberg added.
The FDA, for its part, has expressed strong skepticism regarding elamipretide and Stealth’s supporting data. In a briefing document released earlier this week, internal reviewers cast doubt on the approvability of the drug candidate, pointing out that it fell short of its primary endpoint in the Phase II TAZPOWER trial.
The regulator’s staffers also noted that elamipretide is unlikely to qualify for accelerated approval based on the proposed surrogate biomarker of left ventricle stroke volume, which according to the FDA cannot reliably predict clinical outcomes in Barth syndrome patients.
The FDA is currently reviewing Stealth’s application with a target action date of January 29, 2025.
