The FDA has denied Stealth BioTherapeutics’ request to reconsider its complete response letter, leaving the fate of the biotech and its investigational treatment for an ultrarare genetic disease hanging in limbo.
In a statement to Fierce Biotech, Stealth said the FDA acknowledged “there are no safety concerns, no new efficacy data required on a pre‑approval basis, and that the cited manufacturing facility has been found to be in compliance and did not require corrective action.”
“We have repeatedly sought urgency from the FDA on a viable path forward and have been met with prolonged and consistent delays,” the company added.
As of publication, the federal agency hasn’t responded to Fierce’s request for comment.
Back in May, the FDA issued a complete response letter for Stealth’s elamipretide after the drug had been under priority review at the agency for more than 16 months. The rejection followed several FDA delays and a split advisory committee vote that ultimately favored approval.
Elamipretide secured orphan, fast track and rare pediatric tags for Barth syndrome, an X-linked genetic disorder that weakens the heart and other muscles. The disease primarily affects boys and is thought to impact around one male out of every million born.
The FDA’s recent decision means Stealth will need to submit its third new drug application, a move that would likely see the agency take more than two years to review a data set of 12 patients, according to the biotech.
“Without more immediate action from the FDA, we cannot ensure continued drug availability to this vulnerable community or our sustainability as a company,” the biotech said. “At this time, we are evaluating all options.”
The most recent May rejection already prompted the biotech to lay off 30% of its staff in an effort to save cash for a resubmission.
The drug in question, mitochondria-targeting peptide elamipretide, failed to meet a six-minute walk test endpoint in a clinical trial. Previously, the FDA said Stealth’s data on muscle changes from baseline were “exploratory and uninterpretable.”
Last year, ahead of the October advisory committee, the agency released briefing documents arguing that Stealth’s data package likely isn’t enough to snare approval, even via the agency's accelerated pathway.
Despite this, the independent committee voted 10-6 in support of elamipretide for Barth syndrome.
“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 the open public hearing.
“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.”
“It’s helped a lot. Before, I couldn’t go anywhere and keep up with my friends,” Christopher Pena, a patient with Barth syndrome who has been taking the drug, told NBC affiliate WLBT back in June. “The FDA is making it where there’s a chance for us not to be able to take it.”