SAN DIEGO and KALAMAZOO, Mich., April 12, 2019 /PRNewswire/ -- Cirius Therapeutics announced today that positive results from an interim analysis of exploratory endpoints from the EMMINENCE trial, its ongoing Phase 2b clinical trial evaluating MSDC-0602K in 402 patients diagnosed with non-alcoholic steatohepatitis (NASH) with fibrosis, were presented at The International Liver Congress™ 2019, occurring in Vienna, Austria, from April 10 to 14, 2019.
The interim analysis, which was conducted in the first 328 patients to reach their six-month follow-up visit, demonstrated that patients treated with MSDC-0602K had significant improvements from baseline in measures of liver function and insulin resistance at six months. Key findings from the interim analysis include improvements in liver enzymes, with placebo-corrected reductions at 6 months of 14.3 U/L (p<0.001) and 7.9 U/L (p=0.012) in ALT and AST, respectively, in the 125mg cohort, and 10.6 U/L (p=0.004) and 4.0 (NS) in ALT and AST, respectively, in the 250mg cohort.
In addition, in patients with Type 2 diabetes, all doses of MSDC-0602K were associated with significant improvements in HbA1c, a marker of glycemic control. In this interim analysis, the overall rate of treatment emergent adverse events was similar across placebo and all MSDC-0602K cohorts. A modest, dose-dependent increase in body weight was seen in MSDC-0602K treated subjects, a finding seen with insulin and with other therapies that seek to improve insulin resistance. The rate of peripheral edema observed at six months was similar to that observed at baseline and was comparable across placebo and all MSDC-0602K cohorts.
"We believe these interim results from the EMMINENCE trial, the largest Phase 2b clinical trial to include paired biopsies ever conducted in NASH, support MSDC-0602K's potential to be used in the treatment of NASH with fibrosis, including for those patients with Type 2 diabetes," said Bob Baltera, president and CEO of Cirius Therapeutics. "The improvements in hepatic enzymes observed to date are impressive, especially when combined with the meaningful improvements observed in glycemic control, and we are eagerly anticipating the full data readout, which we expect will occur in the second half of this year."
MSDC-0602K, a second-generation insulin sensitizer, is designed to selectively modulate the mitochondrial pyruvate carrier (MPC), which at the cellular level mediates the effects of overnutrition, a major cause of NASH and other metabolic disorders.
Study Details The EMMINENCE trial is a 12-month, randomized, double-blind, placebo-controlled clinical trial evaluating three oral dose levels of MSDC-0602K. Endpoints of the clinical trial include hepatic histological changes measured by biopsy after 12 months of treatment, changes in liver and metabolic function measured by liver enzymes ALT and AST, markers of liver fibrosis, glycemic control and safety and tolerability. Not all of these endpoints were examined in this interim analysis; rather, in addition to the safety variables of incidence of treatment-emergent adverse events and peripheral edema grades, changes from baseline relative to placebo for a number of exploratory endpoints were examined, including liver functions tests such as ALT and AST, among others, biomarkers and indirect measures of apoptosis and fibrosis, circulating inflammatory markers and markers of bone metabolism, serum triglycerides and fasting cholesterol, markers of insulin sensitivity, and blood pressure.
Dr. Stephen Harrison, the principal investigator in the EMMINENCE trial, presented the interim results at The International Liver Congress during the NAFLD-Clinical Therapy Session held on April 12, 2019 at 5:30 p.m. CET (Abstract PS-111).
About Cirius Therapeutics Cirius is a clinical-stage pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and metabolic diseases. Our lead product candidate, MSDC-0602K, is a novel small molecule being developed as a once-daily oral therapy to treat NASH with fibrosis. MSDC-0602K is designed to selectively modulate the mitochondrial pyruvate carrier (MPC), which mediates at the cellular level the effects of overnutrition, a major cause of NASH and other metabolic disorders. We are conducting a Phase 2b clinical trial of MSDC-0602K, which we have fully enrolled with 402 patients diagnosed with NASH with fibrosis. For more information about Cirius Therapeutics, visit www.ciriustx.com.