The FDA has accepted Stealth BioTherapeutics’ third new drug application for its ultrarare disease candidate, providing a planned decision date of Sept. 26.
The timeline is surprising since the agency considers the resubmission a complete class 2 response, which typically requires a six-month process, and has given Stealth a PDUFA date of Feb. 15, 2026.
The fast approaching September date may reflect a renewed urgency from the agency, which has thrice rejected Stealth’s elamipretide, a peptide designed to treat Barth syndrome, an X-linked genetic disorder that weakens the heart and other muscles. Death rates are highest in the first four years of life, and patients don’t typically live past their 40s.
The sense of newfound urgency is likely fueled by a wide-ranging public outcry surrounding the agency’s several delays and subsequent refusal of the rare disease candidate.
In a June 30 letter, 14 members of Congress urged FDA Commissioner Marty Makary, M.D., to provide clarity about the approval process for elamipretide. Less than a month later, seven Congress members wrote to him again, voicing concern about the regulatory path for the experimental drug.
Just this month, a coalition of physicians and scientists sent Makary another letter asking that he immediately reverse course.
“These delays have brought the drug’s sponsor to the brink of financial collapse, leading to forced withdrawal of our patients from elamipretide as early as September,” the group wrote.
Stealth has said it is considering all options while the company questions its own viability after the rejection. Immediately after receiving the FDA complete response letter, the biotech laid off 30% of its staffers in an effort to save cash.
The earlier decision date provides a sense of hope for Stealth and patients with Barth syndrome alike.
"We appreciate the FDA's timely acceptance and commitment to expeditiously review our NDA resubmission," Stealth CEO Reenie McCarthy said in an Aug. 21 release. "We are sharing this news in the spirit of transparency with families living with Barth syndrome and their many champions, and with gratitude to the FDA for recognizing the urgency of the unmet need."
The resubmission seeks accelerated approval based on improvements in knee extensor muscle strength, an intermediate clinical endpoint, as recommended by the FDA.
The resubmission also includes—at the FDA’s request—information about post-marketing commitments such as a potential trial to confirm elamipretide’s clinical benefit.
All this follows the FDA’s May rejection after a priority review that took more than 16 months. The agency’s decision followed several delays and a split advisory committee vote that ultimately favored approval.
After elamipretide failed to meet a six-minute walk test endpoint in a clinical trial, the FDA previously said certain Stealth data were “exploratory and uninterpretable.”
However, given the rare nature of the disease, others have argued that the standards shouldn’t be the same as those for more common conditions.
“The trials that we’d love to have for Barth syndrome are just not feasible given the rarity of the condition,” Brian Feingold, M.D., a pediatric cardiologist in Pittsburgh, said during last year’s advisory committee meeting.
“The drug has an excellent safety profile, with injection site reactions being the most notable side effect and no life-threatening or potentially life-threatening adverse effects,” said Feingold, who has cared for nine patients with Barth syndrome. “So, to continue to be caught in a catch-22 loop where data on clinically meaningful benefit exists and the adverse effects are relatively trivial in a population that is begging for an opportunity does not make sense to me.”
There are currently no approved therapies for Barth syndrome in the U.S. or the EU.