Mavodelpar in Patients with Primary Mitochondrial Myopathy: a phase 1 trial

Primary mitochondrial myopathies (PMM) are a group of rare, genetically-defined disorders leading todefects of oxidative phosphorylation affecting predominantly, but not exclusively, skeletal muscle.Development of effective treatments is urgently needed. Mavodelpar, a selective peroxisomeproliferator-activated receptor delta (PPARgamma) agonist, was identified as a candidate therapy for PMM.In this Phase 1b, open-label trial to evaluate the safety and tolerability of mavodelpar (primaryobjective), 23 male and female PMM patients (aged 16 years and over) received mavodelpar 100 mg once dailyfor 12 weeks (Part A), with the option of an additional 36 weeks of dosing extension (Part B). Thisreport focuses on the results of Part A of the study but also includes safety experience from Part B.Secondary safety objectives included changes in laboratory and clinical parameters. Additionalobjectives were pharmacokinetics and pharmacodynamics, as well as exploratory efficacy outcomesincluding performance testing, patient-reported outcomes, and muscle biopsy analysis. Muscle biopsy analysis included DNA, protein and mRNA transcriptomic analyses.ClinicalTrials.gov identifier: NCT03862846