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PHARMACOLOGY ALERT

Elamipretide Injection (Forzinity)

October 30, 2025

By William Elliott, MD, FACP, and James Chan, PharmD, PhD

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to elamipretide, the first treatment for Barth syndrome — a life-threatening disease of the mitochondria. Elamipretide is a mitochondrial cardiolipin binder that improves mitochondrial structure and function.1 The accelerated approval is based on improved strength of the muscle used to straighten the leg at the knee.2 Elamipretide was granted priority review and a rare pediatric disease designation. It is distributed as Forzinity by Stealth Biotherapeutics, Inc.

Indications

Elamipretide is indicated to improve muscle strength in adult and pediatric patients weighing at least 30 kg with Barth syndrome.1 The manufacturer is required to conduct a post-approval randomized, double-blind, placebo-controlled trial to confirm patient benefit.2

Dosage

The recommended dose is 40 mg subcutaneously once daily at the same time each day.1 The dose should be reduced to 20 mg daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min and not on dialysis). Elamipretide is available as 280-mg/3.5-mL single-patient-use vials.

Potential Advantages

There currently are no drugs to treat Barth syndrome. Elamipretide is the first FDA-approved treatment for this rare disease with approval based on improvement in muscle strength.

Potential Disadvantages

Elamipretide has a slow onset of action with measurable benefit observed after more than three years of treatment. It is not approved for use in neonates because the formulation contains benzyl alcohol.1 Hypersensitivity reactions, including serious allergic reactions, have been reported.1 The most common adverse drug reactions are local injection reactions, including erythema, induration, pruritus, and pain.1 Two of 10 study participants discontinued the trial because of injection site reactions during the open-label extension phase.3

Comments

Elamipretide is a mitochondrial cardiolipin binder that improves mitochondrial morphology (sustained cristae network) and function (bioenergetic).1,3 It was evaluated in a randomized double-blind, placebo-controlled, crossover trial and its 192-week, open-label, single-arm extension (TAZPOWER).1,3,4 Twelve subjects, all males with genetically confirmed Barth syndrome, were randomized to elamipretide (n = 6) or placebo (n = 6) for 12 weeks. After a four-week washout period, subjects were crossed over to the opposite treatment. This allowed the subjects to serve as their own controls. After completing this phase, subjects entered an open label-extension (OLE) through week 168. Subjects had an average age of 19.5 years, and 92% were white. For part 1 randomization phase, the primary outcomes measured were distance walked in meters during a six-minute walk test (6MWT) and the total fatigue score on the Barth Syndrome Symptom Assessment (BTHS-SA). For the OLE, the primary outcome was long-term safety and tolerability of elamipretide. Secondary outcomes included 6MWT, BTHS-SA scores, and knee extensor muscle strength measured by handheld dynamometry. After part 1, no statistical difference was observed in 6MWT or BTHS-SA total fatigue score. Improvement in knee extensor muscle strength also was not observed. Eight subjects continued into the OLE (10 entered, two dropped out). Improvement in muscle strength was first observed at week 36 but was not sustained. Significant improvements were observed in all subjects at week 168, with a median change of 63 Newtons.1 Improvements in 6MWT, total fatigue score, and measure of left ventricular stroke volume index also were observed.4

However, the FDA’s accelerated approval was based only on the improved strength of the muscle used to straighten the leg at the knee. Elamipretide appears to be well-tolerated. A retrospective, natural history study compared eight subjects from the TAZPOWER study with a propensity-matched 19 untreated patients. The study suggested that elamipretide may meaningfully improve the natural history of Barth Syndrome in skeletal muscle and cardiovascular parameters.5

Clinical Implications

Barth Syndrome is a rare, X-linked, recessive genetic disorder involving mitochondrial cardiolipin metabolism caused by defects in the gene TAFAZZIN. Cardiolipin is involved with the electron transport chain proteins and the membrane structure of the mitochondria. Barth syndrome has a prevalence of about one in 1 million male births. The disease is characterized by prenatal onset of left ventricular non-compaction, cardiomyopathy, intermittent neutropenia, and skeletal myopathy. Premature death results from severe heart failure in infancy.2 Adolescents and adults who survive have low quality of life and high morbidity and mortality. There currently is no approved drug treatment. Because of elamipretide’s pharmacodynamics, long-term treatment is needed to show improved muscle strength and possibly other measures. The cost for elamipretide was not available at the time of this review.

William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.

James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

References

  1. Stealth Biotherapeutics, Inc. Forzinity prescribing information. U.S. Food and Drug Administration. Revised September 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf
  2. U.S. Food and Drug Administration. FDA grants accelerated approval to first treatment for Barth syndrome. Sept. 19, 2025. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-treatment-barth-syndrome
  3. Thompson WR, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med. 2021;23(3):471-478.
  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.
  5. Hornby B, Thompson WR, Almuqbil M, et al. Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome. Orphanet J Rare Dis. 2022;17(1):336.