Elamipretide Hydrochloride

Stealth Biotherapeutics CEO Reenie McCarthy believes the company’s mission aligns with comments from FDA Commissioner Marty Makary, M.D., regarding expedited pathways for rare disease drugs.\n After communicating with the FDA about font sizes for potential packaging on its investigational injection, Stealth Biotherapeutics’ CEO thought approval for the ultrarare genetic disease treatment was imminent.Instead, after more than 16 months under priority review, the FDA issued a complete response letter, rejecting Stealth’s drug elamipretide.“It’s yet another delay after an already missed PDUFA date and an already extended PDUFA date and a really long priority review,” Stealth CEO Reenie McCarthy told Fierce Biotech. “That\'s a head scratcher for me—it doesn\'t seem like the most efficient approach.”After an advisory committee voted in favor of the filing in a split decision back in October, the FDA twice delayed its ruling.“It\'s a shock, because obviously there was a positive adcomm vote, and most of the time—like 97% of the time—the FDA follows positive outcome votes,” the CEO explained, adding that the absence of safety issues and active nature of the review fueled her belief that an approval was right around the corner.In the rejection publicly announced today, the FDA mapped out a path to accelerated approval, agreeing to consider knee extensor muscle strength as a potential intermediate clinical endpoint, the biotech said. Stealth had previously requested that this endpoint be used and had previously submitted data for the measure.“There\'s a paragraph in the CRL literally captioned ‘a path forward,’ that lays out a pretty clear-cut resubmission pathway, as far as we can read it, without requiring much of a resubmission,” McCarthy told Fierce.The agency is asking for a safety update from data emerging over the past year, none of which McCarthy believes will change the safety profile of the drug. “So, there\'s some relief right there, right? I mean, we\'ve stuck with this program because it\'s very hard to walk away from this patient population,” the CEO said. “So, having a path forward is a relief … there’s also some frustration there, because we\'ve been suggesting this for years.”“I just don\'t really understand,” McCarthy said, pointing to a disconnect between the FDA providing a path for accelerated approval and also denying approval for the drug using some of the same data.“It seems like accelerated approval on the basis of muscle strength, data that we already submitted, should have just meant an approval instead of a CRL,” she rationalized.“They’ve done a pretty exhaustive review,” McCarthy said. “We had hundreds and hundreds of information requests and an adcomm. I\'m not sure, the resubmission is a little bit confusing, and I think we\'ll try to understand from the agency if that\'s really the most efficient path here.”  A priority review that took 16.5 months One of the several holdups came through the so-called priority review. Initially, Stealth was set for a standard review cycle, and, while the biotech challenged that to win priority review, the time frame from the standard process remained.After the adcomm vote in October 2024, which ended up 10-6 in support of approval, the FDA asked Stealth for new ad hoc analyses, resulting in hundreds of new outputs, McCarthy said.Stealth submitted all those back in December, according to McCarthy. In January, the agency said the new data constituted a major amendment and pushed the decision back to April.“Even during the major amendment, we were getting information requests in February and in March, so it was a very active review,” the Stealth CEO said. In early April, the FDA told Stealth that they “were likely going to miss the PDUFA date,” McCarthy recounted. “But then they sent us labeling comments a couple days later.”The regulatory agency requested a resubmission for the U.S. package insert in late March and gave Stealth feedback on the cartons the injection would be delivered in, such as changing the font size, in early April. After that, the biotech didn’t receive any communication that would indicate a rejection, according to the CEO. ‘Drain on the company’ Biotechs are lean by design, with shorter cash runways that don’t lend themselves to lengthy delays. Given the further delay, Stealth has decided to lay off 30% of its staff to save cash for a resubmission.“This has been really hard, and the reduction in force that we\'ve done is really intended to prioritize this program,” McCarthy said. “We\'re deprioritizing other programs, you know, not initiating some other activities we planned.”Stealth was strategizing around a January decision and had to defer the launch of other programs as the date got pushed.“If this was going to be the decision and they gave it to us even in January, on the original PDUFA date, we could have been resubmitted by now, right?” McCarthy asked, seemingly at a loss.“But the delays not only push out the timelines, but you\'re also at the same time supporting pre-commercialization activities that you know are a drain on the company that we wouldn\'t otherwise have initiated if we weren\'t essentially getting pretty positive signals from the agency,” she said, citing the late cycle amendment as one of those signals.Stealth turned private in 2022 after the FDA denied approval for the original application for elamipretide, a decision that sent the company’s stock plummeting. The biotech is currently backed by a single large investor, according to the CEO.As far as funding for a potential commercial launch goes, the plan was to monetize a priority review voucher. The delays make those plans more tenuous.  Trusting the FDA  For years, elamipretide has been dragged through regulatory processes.“From 2019 through 2021, we were moved through four FDA review divisions,” the Stealth CEO said. “When we landed in the Division of Cardiology, they told us in a very early meeting that we should submit and they would file an NDA, because they agreed that it wasn\'t feasible to conduct another preapproval trial, or, frankly, they questioned the feasibility of a post-approval trial.”“They changed their mind on that, and we ended up with a refusal-to-file that year,” she said.Back in 2021, the FDA had multiple discussions with Stealth about elamipretide for treating cardiomyopathy in Barth syndrome. The agency said it had expressed skepticism that the data from a phase 3 study could establish the effectiveness of elamipretide and recommended a new trial.Instead, Stealth submitted a new drug application seeking approval of elamipretide, and the FDA issued its refusal-to-file letter, stating that the application didn’t contain a single adequate and well-controlled trial that could establish efficacy.The biotech then informed the agency of its intent to resubmit the NDA—without conducting a new trial.  A new trial launch is difficult in part given the ultrarare nature of Barth syndrome, with only about 130 Americans living with the disease.“Despite our strong belief that this drug is important for this patient population, we do recognize these are small trials,” McCarthy said.Stealth’s resubmission included data from a phase 2 study, an open-label crossover follow-up and a phase 3 trial evaluating elamipretide’s effect in a distance-walked test, among other things. Now, the biotech faces yet another resubmission. But McCarthy believes Stealth’s mission aligns with comments from FDA Commissioner Marty Makary, M.D., regarding the possibility of new expedited pathways for rare disease drugs.The next step is a Type A—or high priority—meeting with the agency, a discussion that McCarthy hopes will take place in late June.If the resubmission is “as straightforward as the agency suggests,” McCarthy believes the process will take about two to six months.When asked about appealing the decision, the Stealth CEO said the focus is on getting the medicine to patients, so if a resubmission is possible, that’s what Stealth intends to do. An appeal of an FDA denial can’t occur simultaneously with a resubmission, she explained.“We are kind of hanging on by our fingernails here to try to bring this drug to the patient community,” she said. “It\'s been a battle at multiple steps of the way, but we just don\'t have a lot of juice left right now.” ‘Act here and act quickly’ Barth syndrome is an X-linked genetic disorder that weakens the heart and other muscles. Death rates are highest in the first four years of life, and about half of children with the disease die by 1 year of age, McCarthy said.“I hope the Barth syndrome community doesn\'t get left behind,” McCarthy said. “This has been a really, really long saga.”“The medical community and the patient community both have been urging the FDA to act here and act quickly,” the CEO added. “I hope it can happen, because there\'s nothing else in the pipeline out there for this disease.”“It’s unconscionable that it now will take even longer for the FDA to rule on this drug for our very small population with no other specific therapies,” Emily Milligan, executive director for the Barth Syndrome Foundation, said in a May 29 statement. “This administration has sent strong signals it’s serious about defining a process that works for rare disease families. Now is the time to deliver. We need FDA leadership to take strong, decisive action and put an end to the hemming and hawing.\"Editor\'s note: This article was updated at 4 p.m. ET to include a statement from the Barth Syndrome Foundation.

Following five years of discussions and a positive advisory committee recommendation, FDA proposes a potential accelerated approval pathway requiring resubmission of the elamipretide NDA Barth syndrome, a progressive, lethal, pediatric cardioskeletal disease often diagnosed at birth and with no approved therapies, affects ~150 individuals in the U.S. NEEDHAM, Mass., May 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") has identified a potential path forward for elamipretide for the treatment of Barth syndrome following years of discussions with the Agency and a 2024 Cardiovascular and Renal Drugs Advisory Committee meeting ("Ad Com") that concluded that elamipretide is effective for the treatment of Barth syndrome. The Company submitted data in its January 2024 new drug application ("NDA") showing that knee extensor muscle strength, which improved by over 45 percent in the Company's Phase 2 clinical trial, was significantly correlated with improvements on the six-minute walk test, an FDA-recognized indicator of clinical benefit. The Company proposed in its NDA and the FDA has now agreed to consider knee extensor muscle strength, for which the Company previously submitted data, as a potential intermediate clinical endpoint to support accelerated approval. "We recognize that the FDA's recommendation for an accelerated approval for elamipretide in Barth syndrome offers a path forward for this incurable pediatric disease that affects an incredibly small number of individuals worldwide," said Reenie McCarthy, CEO. "Elamipretide, which targets the cardiolipin deficit central to Barth syndrome, is the only agent in clinical development to treat this ultra-rare disease for which the FDA has acknowledged that additional pre-approval randomized controlled trials are unfeasible. We hope the FDA will also prioritize ensuring rapid access for neonates affected by the disease subject to appropriate post-marketing safety monitoring. We are experiencing a sharp increase in emergency access requests for critically ill infants from medical experts worldwide following the recent publication of several positive case study reports." Stealth received the FDA's complete response letter after a 16.5-month priority review cycle during which the FDA extended its review from January to April 2025 then missed its April 29 extended prescription drug user fee action date. The FDA also cited observations arising from a May 2025 CGMP surveillance inspection of a third-party manufacturing facility for elamipretide, although no specific deficiencies related to the elamipretide manufacturing process were identified. The FDA did not raise concerns with the clinical safety data, requesting only that a resubmission include any additional safety data collected since NDA submission. The Company will meet with the FDA next month to discuss the proposed post-marketing study, with which the Agency previously expressed alignment when originally proposed by the Company in 2022. The regulatory pathway for this development effort has been complex, entailing four different FDA review divisions since data was first presented to the FDA in 2019. The ultra-rare nature of Barth syndrome, the FDA's reservations regarding the positive data from SPIBA-001, a Phase 3 natural history control study assessing the functional endpoints utilized in the TAZPOWER open-label extension, and the FDA's prior refusal to consider an accelerated approval pathway all contributed to the challenges of the review. In its NDA submission, the Company proposed accelerated approval on the basis of a muscle strength intermediate endpoint to address the FDA's desire, echoed by several members of the Ad Com, to see additional confirmatory data. The FDA's decision to now consider this pathway offers hope for access to treatment for the U.S. Barth syndrome patient community, approximately 20% of whom already receive elamipretide under the Company's expanded access program. However, the Agency has expressed reluctance to extend the accelerated pathway to critically ill neonates, who comprise nearly two-thirds of the Company's expanded access program. Half of early deaths reported in this lethal pediatric disease occur by age one. The FDA's recommendation to resubmit on the basis of this new advice will further delay the potential approval and launch of elamipretide. The Company has implemented a 30% reduction in its personnel to conserve resources to fund a potential NDA resubmission and avoid interrupting patients' access to elamipretide through the Company's expanded access program. About Barth Syndrome Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities 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 5. 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 currently no FDA- or EMA-approved therapies for patients with Barth syndrome. Elamipretide has Orphan Drug, Fast Track, Priority Review, and Rare Pediatric Designation from the FDA and Orphan Drug Designation from the EMA 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. We are also evaluating a topical ophthalmic formulation of our second-generation clinical-stage candidate, bevemipretide (SBT-272), for dry age-related macular degeneration, and have a deep pipeline of novel compounds under evaluation for rare neurological and cardiac disease indications. 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