Barth Syndrome

A US Food and Drug Administration (FDA) panel of experts has voted in support of Stealth BioTherapeutics’ elamipretide for Barth syndrome, an ultra-rare genetic disease that affects approximately 150 people in the US. There are currently no therapies approved by the regulator for Barth syndrome, which primarily occurs in males and is characterised by cardiac abnormalities. The disease leads to muscle weakness, exercise intolerance, fatigue, heart failure, recurrent infections and delayed growth, and is associated with a reduced life expectancy. The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted ten to six in favour of Stealth’s application for elamipretide, concluding that the drug is effective for this patient population. Among the evidence supporting the committee’s decision was positive results from the TAZPOWER part two baseline-controlled extension study, the late-stage SPIBA-001 natural history control study, as well as supportive biomarker and preclinical data. Stealth’s chief executive officer, Reenie McCarthy, said: “We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package… and recognised that this data supports the potential of elamipretide to improve the lives of patients with this devastating disease.” The CRDAC’s vote will now be considered by the FDA as it completes its independent review of elamipretide in this indication, with a final decision expected in January 2025. Elamipretide has already been granted orphan drug, fast track and rare paediatric disease designations by the FDA, as well as orphan drug designation by the European Medicines Agency for Barth syndrome. The drug is also being evaluated in late-stage trials for primary mitochondrial myopathy and dry age-related macular degeneration. Beyond elamipretide, Stealth is evaluating a topical ophthalmic formulation of its clinical-stage candidate bevemipretide for dry age-related macular degeneration, and has a pipeline of compounds under evaluation for rare neurological and cardiac disease indications. The vote on elamipretide comes just one month after the company was awarded a grant from the Friedreich’s Ataxia (FA) Research Alliance to evaluate its mitochondria-targeted molecule SBT-589 in FA, an inherited disease that causes progressive damage to the nervous system and estimated to affect one in 50,000 individuals in the US.

This week, Stealth BioTherapeutics CEO Reenie McCarthy faced a seemingly insurmountable roadblock with the company’s drug for the ultra-rare, fatal mitochondrial disease Barth syndrome. FDA reviewers had extensively questioned the data supporting the drug’s efficacy. And the agency had already turned down Stealth once. Instead, the advisory committee on Thursday voted 10-6 in support of the drug, following testimony from patients and their families, as well as doctors who had treated patients with it. The result was a substantial win for the small, 50-person private company and its CEO. McCarthy joined Endpoints News via Zoom on Friday to discuss the surprise vote. “We’ve had a lot of ups and downs along the way, and we really tried to keep progressing the program despite some of the disappointments because of the strong belief that we had a drug that was working for patients living with this terrible disease,” McCarthy said. Barth syndrome affects about 130 American boys, and 80% don’t survive past 5 years of age. However, Stealth’s proposed indication for the drug is for 12 years and older, and the population in which the drug was studied was mostly older teenagers and children. “That’s an FDA decision,” McCarthy said, noting there are about 20 to 25 boys on the drug through an expanded access program. “We certainly profiled some of our expanded access in our presentation, really to speak to the safety that we’ve seen in younger children.” She said the company has had requests for the drug from 10 countries and a dozen US hospitals, noting patients and their families don’t pay for treatment under those expanded access efforts. The FDA has until Jan. 29, 2025, to make a final approval decision. McCarthy declined to discuss potential pricing ahead of an elamipretide approval, and said the company plans to conduct a pharmacokinetic study in younger children to optimize dosing. “You know what the price tags of drugs for super-rare diseases are,” McCarthy said. “We’re going to have to take that into consideration. But super-rare diseases are a little bit less of a problem from a payer perspective as well, because there’s a lot less patients affected by them.” CDER Director Patrizia Cavazzoni, who typically doesn’t speak at advisory committee meetings, made a comment just prior to Thursday’s vote about regulatory flexibility and how the agency is evolving its work in ultra-rare indications. McCarthy said it was the first time anyone in the FDA’s leadership had indicated that there might be some flexibility afforded to elamipretide.

Advisory Committee Voted 10 to 6 in Favor, Concluding that Elamipretide is Effective for the Treatment of Barth Syndrome Elamipretide NDA Received Priority Review with a PDUFA Action Date of January 29, 2025 If Approved, Elamipretide Would Be the First Therapy for Barth Syndrome, a Life-Threatening Ultra-Rare Mitochondrial Disease NEEDHAM, Mass., Oct. 11, 2024 /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") Cardiovascular and Renal Drugs Advisory Committee ("CRDAC") voted 10 to 6 in favor of Stealth's New Drug Application ("NDA"), concluding that elamipretide is effective for the treatment of patients with Barth syndrome. The CRDAC discussed the benefits and risks of elamipretide for the treatment of Barth syndrome, including results from the TAZPOWER Part 2 baseline-controlled extension study, the SPIBA-001 Phase 3 natural history control study, and additional supportive biomarker and preclinical data. The CRDAC's vote, while not binding, will be considered by the FDA when making its decision regarding the potential approval of elamipretide for Barth syndrome. If approved, elamipretide would be the first therapy for this ultra-rare, progressive, life-shortening, cardioskeletal disease that affects approximately 150 individuals in the United States. The NDA for elamipretide was granted priority review and has been assigned a Prescription Drug User Fee Act ("PDUFA") action date of January 29, 2025. "We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package – including the positive results from the rigorously constructed natural history control trial, the durable open-label extension data, and expanded access cases – and recognized that these data support the potential of elamipretide to improve the lives of patients with this devastating disease," said Reenie McCarthy, Chief Executive Officer. "We are grateful to the many patients, caregivers, advocates, and healthcare providers who shared their perspectives and experiences with the advisory committee. We look forward to collaborative conversations with the FDA as the agency completes its review of elamipretide, the first potential therapy for Barth syndrome." If approved, this would be the first marketing authorization for elamipretide, a first-in-class mitochondria-targeted therapeutic. In addition to Barth syndrome, elamipretide is in Phase 3 trials for primary mitochondrial myopathy, with pivotal data expected by the end of 2024, and for dry age-related macular degeneration. 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 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