Indications

Elamipretide is a first-in-class mitochondrial targeted therapeutic being developed for the treatment of diseases associated with mitochondrial dysfunction (e.g., Barth syndrome, primary mitochondrial myopathy). On April 8, 2024, the FDA announced that it had accepted the new drug application for elamipretide for the treatment of Barth syndrome, making it the only drug in late-stage clinical development for Barth syndrome. Barth syndrome is a rare and potentially fatal X-linked disease characterized by cardiomyopathy, skeletal muscle weakness, growth retardation, and cyclical neutropenia. Patients with Barth syndrome are at high risk of death in infancy and are prone to developing cardiomyopathy and a severely weakened immune system. Elamipretide topical ophthalmic solution is also used to treat Leber hereditary optic neuropathy (LHON).

Mechanism of Action

Elamipretide is a water-soluble, aromatic-cationic, mitochondrial-targeted tetrapeptide that easily permeates and transiently localizes to the inner mitochondrial membrane. Treatment with Elamipretide promotes cellular health by improving energy production and inhibiting the excessive formation of reactive oxygen species, thereby alleviating oxidative stress. It crosses the outer membrane of mitochondria and binds to the constituent phospholipid cardiolipin of the inner membrane, enhancing ATP production and reducing the leakage of reactive oxygen species, thereby improving left ventricular relaxation by improving mitochondrial dysfunction, achieving the treatment of adolescent and adult Barth syndrome patients.

Side Effects

Studies have shown that subcutaneous Elamipretide is generally safe/well tolerated, but most subjects reported injection site reactions (ISRs) such as pain, nodules, swelling, and itching at the injection site. The other most common adverse events were headache and dizziness. For participants who received the highest dose of elamipretide or placebo, the most common adverse event was headache.

References:

[1] SULLIVAN A, BERGHEANU S, KROPP L, et al. Interventions with Potential to Mitigate Injection Site Reactions Following Subcutaneous Elamipretide Administration: A Phase 1, Crossover Study[J]. Authorea (Authorea), 2023, 127 1: 0. DOI:10.22541/au.168075727.77826241/v1.

[2] SABBAH H N. Elamipretide for Barth syndrome cardiomyopathy: gradual rebuilding of a failed power grid.[J]. ACS Applied Energy Materials, 2022: 1911-1923. DOI:10.1007/s10741-021-10177-8.

[3] MD R K, PHD; Alfredo A S M, PHD. Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy[J]. Ophthalmology, 2023, 131 4: Pages 422-433. DOI:10.1016/j.ophtha.2023.10.033.

[4] HANI N SABBAH; Hilary J V; Carolyn Taylor. Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide.[J]. Future cardiology, 2023, 19 4: 211-225. DOI:10.2217/fca-2023-0008.