Long-term Efficacy and Safety of Elamipretide in Patients with Barth Syndrome: 168-Week Open-label Extension Results of TAZPOWER.

PURPOSE: Evaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS) .

METHODS: TAZPOWER was a 28-week randomized, double-blind, placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40mg 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. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed.

RESULTS: 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 timepoints (cumulative 96.1 meters of improvement [Week 168, p=0.003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE timepoints. 3-D 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.

CONCLUSION: Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.