An approval decision for Stealth BioTherapeutics’ investigational treatment for an ultra-rare genetic disease has been delayed—again—this time, with no new decision date given.
The biotech’s candidate, called elamipretide, had a Prescription Drug User Fee Action (PDUFA) date scheduled for today. However, the FDA said it wouldn’t meet the new drug application (NDA) deadline and didn’t give a new action date, according to an April 29 release from Stealth.
"The FDA cannot comment on any pending application to preserve the integrity of the review process," a spokesperson for the Department of Health and Human Services told Fierce Biotech on Tuesday night. "If you are seeking information about a drug that is not approved, this information is confidential but may be publicly disclosed by the sponsor."
"Any delays in drug approvals are the result of the FDA’s rigorous review process, which is designed to ensure that all medications are safe and effective for the American people," the government spokesperson added. "These delays are not connected to the recent reorganization."
This isn’t the first FDA delay related to elamipretide, an injection designed to treat Barth syndrome, a life-threatening pediatric mitochondrial disease thought to impact less than 300 individuals globally.
Stealth submitted an NDA on Jan. 29 of last year and received a PDUFA date of Jan. 29, 2025, under the standard review process. Later, the FDA granted the therapy priority review, with an advisory committee voting 10-6 in support of approving the drug in October.
However, the FDA requested a three-month delay in January to review additional data supplied by Stealth. The FDA said the data counted as a major amendment to the approval request, triggering the standard three-month extension to the decision timeline.
Now, while the FDA hasn’t shared a new expected action date, Stealth says labeling discussions between the agency and Massachusetts biotech are currently underway.
“Despite the delay, Stealth remains optimistic and continues to engage with the FDA in this active review,” a Stealth spokesperson told Fierce Biotech. “Most important to address is the urgent need of those requiring expanded and emergency access to elamipretide.”
The FDA previously granted elamipretide orphan drug, fast track and rare pediatric designations for Barth syndrome. But in October, the agency took issue with several parts of Stealth’s trials, saying that certain data were difficult to interpret and citing a potential placebo effect in the late-stage trial.
“No other trial designs that had been discussed… were ultimately acceptable to FDA, primarily due to powering concerns that are frankly insurmountable in a disease that's rare,” Stealth CEO Reenie McCarthy said during the nine-hour advisory hearing.
While Stealth isn’t the first biotech to experience delays since the Trump administration rapidly restructured the FDA, this also isn’t the first time Stealth has asked the agency to approve elamipretide.
The original application for the injection was tied to a phase 3 study, called SPIBA-001, that trial met its main goal. However, the data were compared to an open-label portion of a phase 2/3 crossover study and natural history controls—a strategy the FDA did not like.
Back in 2021, the FDA said it expressed skepticism that the Stealth data could establish the effectiveness of elamipretide and recommended that Stealth launch a new phase 3 trial.
Despite this, Stealth submitted an NDA seeking approval, prompting the FDA to issue a refusal-to-file letter, stating that the application didn’t contain a single adequate and well-controlled trial that could establish efficacy.
The FDA continued to recommend a new late-stage trial, but Stealth informed the agency of its intent to resubmit the NDA without conducting a new trial. The regulator said it could not prevent an applicant from resubmitting and that Stealth should fully address the agency’s prior concerns in the resubmission.
Editor's note: This story was updated at 9 a.m. ET on April 30 to include comment from HHS.