Effects of Elamipretide in Adults with Primary Mitochondrial Myopathy: a Phase 2 Double-Blind, Randomized, Placebo-Controlled Crossover Trial (MMPOWER-2) (S5.003)

Objective: In MMPOWER, a study of patients with genetically confirmed Primary Mitochondrial Myopathy (PMM), intravenous elamipretide (ELAM) for five days increased the distance walked versus placebo during the 6-Minute Walk Test (6MWT) in a dose dependent fashion. The current study (MMPOWER-2) evaluated the effect of 4-weeks of subcutaneous ELAM on several functional and patient-reported assessments. Background: Common symptoms of fatigue, exercise intolerance, and muscle weakness in adults with PMM adversely affect physical functioning and quality of life. ELAM is an aromatic-cationic tetrapeptide that readily penetrates cell membranes and transiently localizes to the inner mitochondrial membrane where it associates with cardiolipin, improving ATP production and exercise capacity. Design/Methods MMPOWER subjects (N=30) were randomized (1:1) to either 4 weeks of daily ELAM 40 mg (treatment-period 1), then 4 weeks of matching placebo in treatment-period 2 (4-week washout in-between), or vice versa to evaluate the distance walked during the 6MWT (primary endpoint), and other functional assessments, patient-reported questionnaires, and safety assessments (secondary endpoints). Results: The distance walked in the 6MWT improved by 19.8 meters compared to placebo with daily ELAM 40 mg at the end of the treatment period (P=0.0833). At end of treatment, ELAM-treated subjects who walked Conclusions: Subjects who received daily ELAM for 4 weeks had an improvement in their 6MWT and patient reported outcomes; therefore, a phase 3 trial will be initiated. Study Supported by: Stealth BioTherapeutics Disclosure: Dr. Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Stealth Biotheraputics. Dr. Karra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Stealth BioTherapeutics. Dr. Karra has received research support from Stealth BioTherapeutics. Dr. Haas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Stealth BioTherapeutics. Dr. Haas has received research support from Stealth BioTherapeutics. Dr. Goldstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Stealth BioTherapeutics. Dr. Goldstein has received research support from Stealth BioTherapeutics. Dr. Vockley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Stealth BioTherapeutics. Dr. Vockley has received research support from Stealth BioTherapeiutics.