FDA Grants Accelerated Approval to Elamipretide, First Treatment for Barth Syndrome

The FDA granted accelerated approval to elamipretide (Forzinity; Stealth BioTherapeutics) injections in adult and pediatric patients with Barth syndrome weighing at least 30 kilograms to improve muscle strength. With this action, elamipretide has become the first treatment for this disease.^1,2

Barth syndrome is a life-limiting pediatric mitochondrial cardioskeletal disease that affects approximately 150 individuals in the US, primarily males. It typically starts with severe heart failure in infancy and causes premature death. Patients who survive into adolescence and adulthood often have fatigue, poor stamina, and exercise intolerance. Because of Barth syndrome, the quality of life and daily functioning of patients are significantly affected throughout their lives.^1,2

Elamipretide previously received orphan drug, priority review, and rare pediatric designations from the FDA and orphan drug designation from the European Medicines Agency for the treatment of Barth syndrome. This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical end point.^1,2

“The FDA remains committed to facilitating the development of effective and safe therapies for rare diseases and will continue to work diligently to help ensure patients with rare diseases have access to innovative treatments," George Tidmarsh, MD, PhD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release.¹

The accelerated approval is supported by efficacy and safety data from the TAZPOWER clinical trial (NCT03098797)³, a randomized, double-blind, placebo-controlled phase 2 trial that evaluated the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in patients with Barth syndrome.^1-3 The trial is comprised of 2 parts: a randomized, double-blind, placebo-controlled, crossover to assess safety, tolerability, and efficacy of single daily doses of 40 mg administered for a 12-week period (part 1); and an open-label extension (OLE) trial to assess long-term safety, tolerability, and longitudinal trends in efficacy for up to 192 weeks (part 2).³

Results from the open-label extension phase were published in July 2024 in Genetics in Medicine.⁴ Among the 10 patients who entered the OLE, 8 reached the week 168 visit. The investigators observed that elamipretide was well tolerated, with injection-site reactions being the most common adverse event. Significant improvements from the OLE baseline on the 6-minute walk test occurred at all OLE time points (cumulative 96.1 m of improvement [week 168, P = .003]).

Additionally, the mean BarTH Syndrome Symptom Assessment Total Fatigue scores were below baseline (improved) at all OLE time points. Three-dimensional left ventricular stroke, end-diastolic, and end-systolic volumes also improved, showing significant trends for improvement from baseline to week 168. Both monolysocardiolipin and cardiolipin values showed improvement, correlating to important clinical outcomes.⁴

“The approval of [elamipretide], the first treatment option for Barth syndrome and the first approved mitochondria-targeted therapeutic, is a pivotal victory for the Barth syndrome community and offers hope for expedited regulatory attention to other ultra-rare diseases,” Reenie McCarthy, CEO of Stealth BioTherapeutics, said in a news release. “We plan to continue providing expanded access to children weighing less than 30 kg who are currently receiving treatment or require emergency access, while we work with the FDA to generate data needed to expand the indication to include these children. We are committed to the continued development of therapies to treat all patients with Barth syndrome and other devastating diseases of mitochondrial dysfunction.”²

REFERENCES

1. US Food & Drug Administration. FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. News release. September 19, 2025. Accessed September 22, 2025. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-treatment-barth-syndrome?utm_medium=email&utm_source=govdelivery

2. Stealth BioTherapeutics. Stealth BioTherapeutics Announces FDA Accelerated Approval of FORZINITY™ (elamipretide HCl), the First Therapy for Progressive and Life-limiting Ultra-rare Genetic Disease Barth Syndrome. News release. September 19, 2025. Accessed September 22, 2025. https://stealthbt.com/stealth-biotherapeutics-announces-fda-accelerated-approval-of-forzinity-elamipretide-hcl-the-first-therapy-for-progressive-and-life-limiting-ultra-rare-genetic-disease-barth-syndrome/

3. A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome (TAZPOWER). ClinicalTrials.gov identifier: NCT03098797. Updated April 16, 2024. Accessed September 22, 2025. https://www.clinicaltrials.gov/study/NCT03098797

4. Thompson WR, Manuel R, Abbruscato A, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138. doi:10.1016/j.gim.2024.101138