The U.S. Food and Drug Administration (FDA) has accepted Stealth BioTherapeutics’ third new drug application (NDA) for elamipretide, its experimental treatment for Barth syndrome, with a decision date scheduled for September 26.
The timeline is notable, as the agency classified the resubmission as a complete class 2 response, which generally carries a six-month review process. Under this classification, the Prescription Drug User Fee Act (PDUFA) target date would ordinarily fall on February 15, 2026. The September deadline represents an accelerated pathway, reflecting a significantly shortened timeframe.
Elamipretide, a mitochondria-targeted peptide, is designed to address Barth syndrome, an X-linked genetic disorder that leads to cardiac and muscular weakness. The condition carries high mortality in early childhood, with about 85% of patients dying by age five, and life expectancy rarely extending beyond the fourth decade.
The FDA’s decision to expedite review follows a history of setbacks for Stealth, as the agency has previously rejected elamipretide three times. The drug’s regulatory path has been the subject of public attention, with advocates highlighting the urgent need for treatment options.
In June, 14 members of Congress wrote to FDA Commissioner Marty Makary, M.D., seeking clarity on the drug’s review process. A month later, seven lawmakers again urged the agency to address concerns, and earlier this month, a coalition of physicians and scientists sent a letter pressing for reversal of previous refusals.
“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 of physicians and scientists stated.
Stealth has indicated that it is assessing strategic options following recent regulatory challenges. After the FDA issued its most recent complete response letter in May, the company laid off 30% of its workforce to conserve cash. The earlier September decision date now provides what the company describes as renewed hope.
“We appreciate the FDA’s timely acceptance and commitment to expeditiously review our NDA resubmission,” said Stealth CEO Reenie McCarthy in an August 21 release. She noted that the company shared the 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 endpoint that the FDA has accepted. This measure is associated with functional improvements in walking ability. Stealth’s Phase II TAZPOWER trial demonstrated a greater than 45% improvement in knee extensor muscle strength, forming the basis of the company’s application. The FDA has also requested inclusion of post-marketing commitments, such as a confirmatory trial to validate clinical benefit.
The drug’s regulatory history includes a 16-month priority review that ended in rejection this May, despite a split advisory committee vote that ultimately favored approval. While the FDA raised concerns over the interpretability of clinical data, supporters argued that traditional trial standards are difficult to meet due to the rarity of Barth syndrome.
During last year’s advisory meeting, pediatric cardiologist Brian Feingold, M.D., emphasized the drug’s safety and the limitations of conducting large trials. He noted that while injection site reactions were the most common side effect, there were no life-threatening adverse events, and that patients with Barth syndrome are “begging for an opportunity.”
Elamipretide is also in development for primary mitochondrial myopathy and dry age-related macular degeneration, but Barth syndrome remains the company’s lead indication. The FDA’s upcoming decision will determine whether the drug secures its first approval.
