The MPC facilitates entry of pyruvate into the Krebs cycle and in the setting of over nutrition, is critical to adverse manifestations including T2D and NASH. MSDC-0602K is a novel insulin sensitizer engineered to modulate pyruvate utilization with minimal ppar-γ activity. The EMMINENCE study is examining its effects on NASH and glycemia. U.S. sites (57) enrolled 402 patients with liver biopsy evidence of NASH and fibrosis; >50% of subjects with T2D (not taking insulin/pioglitazone) with entry HbA1c ≤ 9.5%. Randomization was 1:1:1:1 to daily oral doses of MSDC-0602K (62.5, 125, and 250mg) or placebo. Safety and glycemia were examined when 328 subjects reached 6 mo visit: 59% female, median age 57, 52% diabetic. (See Table) No meaningful changes in lipids, heart rate or BP were noted. The % of subjects reporting 1 or more adverse events was equal across all 4 cohorts. Importantly, the frequency of peripheral edema was 11% at baseline and unchanged across cohorts at 6 months. MSDC-0602K shows potent effects on glycemic control parameters and insulin sensitization with modest expected weight gain and no evidence of peripheral edema at 6 months, a key ppar-γ related side effect of first generation TZDs. This drug shows promise for glycemic control in NASH patients with T2D/insulin resistance.
K. Cusi: Consultant; Self; Allergan, AstraZeneca, Genentech, Inc., Novo Nordisk Inc., Poxel SA, ProSciento. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Research & Development, Novartis AG, Novo Nordisk Inc. O.G. Kolterman: Advisory Panel; Spouse/Partner; Intarcia Therapeutics, Inc. Advisory Panel; Self; Zafgen, Inc. Board Member; Self; American Diabetes Association, GlySens Incorporated, Viacyte, Inc. Consultant; Self; ADOCIA, Cirius Therapeutics Inc, DiaVacs Inc, JDRF, Nanoprecisionmedical, NuSirt Biopharma, Inc., Renova Therapeutics, Sensulin, LLC. Employee; Self; Whole Biome Inc. Stock/Shareholder; Self; Corcept Therapeutics, GI Therapeutics, Xeris Pharmaceuticals, Inc. Other Relationship; Spouse/Partner; American Diabetes Association. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc. H.C. Dittrich: Employee; Self; Cirius Therapeutics.