Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER

• Published in: Genetics in medicine Vol. 26; no. 7; p. 101138
• Main Authors: Thompson, William R., Manuel, Ryan, Abbruscato, Anthony, Carr, Jim, Campbell, John, Hornby, Brittany, Vaz, Frédéric M., Vernon, Hilary J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Barth syndrome; Cardiolipin; Cardiomyopathy; Elamipretide; Mitochondrial disease; Barth syndrome; Cardiolipin; Elamipretide; Cardiomyopathy; Mitochondrial disease
• ISSN: 1098-3600; 1530-0366; 1530-0366
• DOI: 10.1016/j.gim.2024.101138

Evaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS). TAZPOWER was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40 mg subcutaneous daily. OLE primary endpoints were safety and tolerability; secondary endpoints included change from baseline in the 6-minute walk test (6MWT) and BarTH Syndrome Symptom Assessment (BTHS-SA) Total Fatigue score. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed. Ten patients entered the OLE; 8 reached the week 168 visit. Elamipretide was well tolerated, with injection-site reactions being the most common adverse events. Significant improvements from OLE baseline on 6MWT occurred at all OLE time points (cumulative 96.1 m of improvement [week 168, P = .003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE time points. Three-dimensional (3D) left ventricular stroke, end-diastolic, and end-systolic volumes improved, showing significant trends for improvement from baseline to week 168. MLCL/CL values showed improvement, correlating to important clinical outcomes. Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.