According to reporting from Reuters, reviewers at the agency pointed to an inability to differentiate from placebo to justify rejecting the drug, but an FDA office director approved the drug anyway.
The FDA overruled its reviewers when approving Stealth Biotherapeutics’ Barth Syndrome drug, despite questions about the efficacy achieved in a 10-patient clinical trial, according to documents related to the approval.
That approval came in September after Stealth had unsuccessfully tried to get elamipretide, now sold under the brand name Forzinity, across the finish line for years. Documents from the FDA show that Hylton Joffe, the FDA’s director of the office of cardiology, hematology, endocrinology and nephrology, signed off on the drug under the accelerated approval pathway. The approval was based on a 10-person study that showed the drug improved knee strength.
However, reviewers at the FDA pointed out that the study, which was not placebo-controlled, did not directly link Forzinity to the patient improvements. Reviewers also pointed out that in the TAZPOWER trial, patients taking placebo improved about as much as those taking the drug in a test of how far they could walk in six minutes.
Charu Gandotra, a cardiologist and FDA clinical team leader, also recommended against approving Forzinity to Joffe.
The FDA’s actions were first reported Wednesday by Reuters.
The feelings at the FDA seemed to be broadly mixed in parallel with the drug’s years-long journey to approval. The FDA declined to consider the drug for full approval back in 2021. In 2024, an advisory committee voted 10-6 in favor of supporting the drug for approval, though even the committee members who were in favor were equivocal in their support.
“This was just impossible,” Gerard Berry, professor of Pediatrics at Harvard Medical School and one of the members who voted in favor of the drug, said at the time. “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.”
Stealth was again rejected by the FDA in May, but the agency suggested the company resubmit under the accelerated pathway. Stealth did so, without submitting new data but addressing manufacturing and safety concerns brought up by the FDA in its prior review.
Barth Syndrome is an ultra-rare disease affecting 150 people in the entire U.S. It arises from a genetic mutation affecting patients’ mitochondria, resulting in cardiac abnormalities that lead to muscle weakness and debilitating fatigue. Most patients die by the age of five. Forzinity is the first ever approved treatment for the condition.
The Trump administration has repeatedly advocated for getting more approvals for rare diseases, and the Barth Syndrome patient community rallied to support Forzinity .
“We have everything at stake in this,” Kate McCurdy, board chair at the Barth Syndrome Foundation, told BioSpace in September. “It’s not just hearsay or sort of wishful thinking that we see the benefits of this drug. We can see it.”
This is not the first time that an FDA head has approved a contentious drug for a disease lacking treatment options. In 2023, Peter Marks, the former head of the agency’s Center for Biologics Evaluation and Research, approved Sarepta Therapeutics’ Elevidys for Duchenne muscular dystrophy, despite recommendations from reviewers to decline the treatment.
