Use of Elamipretide in Patients Assigned Treatment in the Compassionate Use Program: Case Series in Four Rare Orphan Diseases

Abstract Background:Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling. There are no US Food and Drug Administration (FDA)–approved therapies for these conditions. Elamipretide is a cell-permeable peptide that has been shown to target the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. Elamipretide has been evaluated in adult and adolescent patients with mitochondrial disorders such as primary mitochondrial myopathy and Barth syndrome, producing clinical and functional improvements. There is little experience with elamipretide in younger patients and those with other mitochondrial diseases. Results:We describe the use of elamipretide in a series of patients with various mitochondrial disorders providing insight regarding dosing of the drug for these patients, especially dosing in young patients. Conclusions:Based on our experience, a dose of approximately 0.5 mg/kg/day is well tolerated in pediatric patients aged < 12 years.