Barth Syndrome

The biotech’s candidate, called elamipretide, had a PDUFA date scheduled for April 29.\n 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 did not return Fierce Biotech’s request for more information about the change.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.

- FDA decision on elamipretide for the treatment of Barth syndrome delayed - - Labelling discussions underway, but no revised action date communicated by FDA - NEEDHAM, Mass., April 29, 2025 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced that the U.S. Food and Drug Administration (FDA) communicated that it would not meet today's prescription drug user fee action (PDUFA) date for its new drug application (NDA) for its investigational medicine, elamipretide, for the treatment of Barth syndrome. Barth syndrome is an ultra-rare, life threatening pediatric mitochondrial disease which is known to affect less than 150 individuals in the United States and less than 300 individuals worldwide. "We appreciate the diligent efforts of the FDA to progress its review of our new drug application, including its confirmation of post-marketing requirements and its recent initiation of labeling discussions," said Reenie McCarthy, Chief Executive Officer. "We hope to gain more information on the revised action date in the coming days to inform our ability to continue supporting expanded and emergency access to elamipretide while advancing towards a potential FDA approval." Stealth's NDA was submitted to the FDA on January 29, 2024 and filed by the FDA for standard review on March 29, 2024 with a PDUFA date of January 29, 2025. On May 6, 2024, FDA granted priority review. On October 10, 2024, the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) met and concluded that elamipretide is effective for the treatment of patients with Barth syndrome. On January 14, 2025, the FDA notified Stealth that new analyses requested by FDA in late November and early December 2024 required a delay of the PDUFA date to April 29, 2025. Elamipretide has received Orphan Drug, Fast Track, Priority Review, and Rare Pediatric Designations from the FDA and Orphan Drug Designation from the European Medicines Agency (EMA) for the treatment of Barth syndrome. More than 35 patients worldwide have received expanded or emergency access to elamipretide for the treatment of Barth syndrome, including many critically ill infants and toddlers affected by the disease. About Barth Syndrome Barth syndrome is an ultra-rare genetic mitochondrial disease leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age five. Barth syndrome occurs primarily in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are no approved therapies for the treatment of Barth syndrome. About Stealth BioTherapeutics Our mission is to develop novel therapies to improve the lives of patients living with diseases of mitochondrial dysfunction. Our lead product candidate, elamipretide, is under review for Barth syndrome and in late-stage development for primary mitochondrial myopathy and dry age-related macular degeneration, where we observed a highly protective effect on photoreceptor loss in Phase 2. We are evaluating a topical ophthalmic formulation of our second-generation clinical-stage candidate, bevemipretide (SBT-272), for dry age-related macular degeneration. We have a deep pipeline of novel compounds under evaluation for rare neurological, cardiac and myopathic diseases. Media Contact Anna Stallmann Communications Anna Stallmann [email protected] Investor Contact Precision AQ Austin Murtagh [email protected] SOURCE Stealth BioTherapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

The fate of a small, privately-held biotech’s new drug has been delayed, in what appears to be a sign that broad cuts to the FDA by the Trump administration may be affecting key regulatory decisions. Stealth BioTherapeutics said the FDA would not meet its Tuesday deadline for approving or rejecting the company’s drug, elamipretide. It had been seeking regulatory clearance of elamipretide for a rare disease called Barth syndrome, which affects only about 150 people in the US and causes heart abnormalities and muscle weakness. About 85% of patients don’t make it past the age of 5. In a statement Tuesday, Stealth said that “the U.S. Food and Drug Administration (FDA) communicated that it would not meet today’s prescription drug user fee action (PDUFA) date for its new drug application.” A person familiar with the situation said the company hadn’t been asked to run more trials or provide more data, that the FDA hadn’t identified any safety concerns, and that the agency hadn’t raised manufacturing issues — typical reasons for why it might reject a drug. All the company knows is that the review is “active,” the individual said. There is no timeline for when elamipretide might be approved or rejected, according to the individual, who spoke to Endpoints News under condition of anonymity. The drug would be the first approved to treat Barth syndrome in the US. Asked about possible FDA delays, an HHS spokesperson said that “the FDA is on track to reach its PDUFA targets. Just for clarity, they are not deadlines as some has reported, they are targets. Scientists have at times said that individual targets will or won’t be met due to the complexity of certain product applications. FDA would rather have a sound decision and it’s been a long-standing practice that some fraction of product decisions are made after the PDUFA target date. FDA is confident they will be met.” Typically, the FDA does not miss PDUFA dates unless it requests more data or raises safety or manufacturing concerns. Those sorts of delays are usually communicated to the companies with new decision dates. The apparent delay comes in the middle of a period of huge upheaval across FDA and other US health agencies under Robert F. Kennedy Jr. The new HHS secretary and Elon Musk’s DOGE have fired thousands of staffers from the FDA, ousted CBER Director Peter Marks, and are looking at consolidating offices across the agency. While it’s been speculated that mass changes would lead to delays and other issues with drug regulation, few outward signs of disruption have surfaced in the first few weeks. That includes the approval of Regeneron and Sanofi’s blockbuster Dupixent in an additional indication , and a label update for Alnylam’s Amvuttra. That may not last, however. One current FDA employee who requested anonymity previously confirmed to Endpoints that “hundreds” of drug and device reviewers have recused themselves to look for new jobs. Former FDA Commissioner Scott Gottlieb made similar comments in a CNBC interview last week. The company had an original decision deadline of Jan. 23, but the FDA requested more time to review material from an advisory committee meeting that generated surprise support from a panel of outside experts. In a statement Tuesday morning, the Barth Syndrome Foundation called on the FDA to move forward on Stealth’s application as soon as possible. “We are deeply disappointed by this further delay but remain hopeful the FDA is taking the time needed to complete a thorough and thoughtful review,” executive director Emily Milligan said. The FDA is expected to decide on a number of drug and biologics applications this week. In addition to Stealth, other companies with PDUFA dates before Friday include Abeona Therapeutics — which received an approval early Tuesday morning — and Satsuma Pharmaceuticals. Abeona is developing a gene therapy for a rare genetic skin disease, while Satsuma is working on a new migraine drug. A decision for Johnson & Johnson’s rare disease drug nipocalimab is also expected by Tuesday, based on when the company filed for approval last year, though J&J has not publicly confirmed a PDUFA date. So far, there has been no indication that the FDA will miss these PDUFA deadlines, and the reason for Stealth’s delay may not be immediately apparent. Despite the broad scope of the Trump administration’s cuts to the FDA, some review offices have remained largely intact, like the Oncology Center of Excellence, while others appear to have been significantly affected. That could complicate certain regulatory processes beyond drug approvals as well. In addition to reviewing applications for new drugs, FDA staffers are also involved in approving new trials and reviewing trial design, looking over preclinical testing, holding advisory committees, finalizing label language and a wide range of other processes that are crucial to drug development. Editor’s note: This story has been updated to include comment from the Barth Syndrome Foundation and information about Abeona’s drug approval.