Therapeutic improves liver function, insulin resistance in NASH phase 2b trial

Interim analysis results from a phase 2b trial of MSDC-062K for patients with nonalcoholic steatohepatitis and fibrosis showed significant improvements in liver function and insulin resistance at 6 months compared with baseline, according to a press release from Cirius Therapeutics.

MSDC-0602K is a second-generation insulin sensitizer designed to selectively modulate the mitochondrial pyruvate carrier (MPC).

“The interim results from the Emminence trial, the largest phase 2b clinical trial to include paired biopsies ever conducted in NASH, are compelling,” Stephen Harrison, MD, medical director of Pinnacle Clinical Research, San Antonio, and principal investigator of the trial, said in the release. “The improvements in hepatic enzymes observed to date are impressive, especially when combined with the meaningful improvements in glycemic control.”

The interim analysis included 382 of the 402 patients enrolled in the study who reached their 6-month follow-up visit. The average nonalcoholic fatty liver disease activity score at baseline was 5.3, 60% of the patients had baseline fibrosis scores of 2 or 3, and approximately 50% had type 2 diabetes at baseline.

Compared with patients who received placebo, patients treated with 125 mg of MSDC-0602K had significant reductions in alanine aminotransferase (14.3 U/L; P < .001) and aspartate aminotransferase (7.9 U/L; P = .012). Those treated with 250 mg of MSDC-0602K also showed a significant reduction in ALT (10.6 U/L; P = .004).

Additionally, the researchers observed significant improvement in fasting glucose, HbA1c, insulin levels, homeostatic model assessment of insulin resistance, and normalization of hepatic enzymes at both 125 mg and 250 mg dose levels.

The overall rate of treatment-related adverse events was similar between placebo and treatment groups.

“We believe these interim results around improved measures of liver function and glycemic control, together with the preliminary adverse event profile, support MSDC-0602K’s potential to be used in the treatment of NASH with fibrosis,” Howard Dittrich, MD, chief medical officer of Cirius Therapeutics, said in the release. “These results support the view that therapies directed toward the MPC have the potential to achieve insulin sensitizing pharmacology with an improved profile over first generation insulin sensitizers. We look forward to presenting full data to the scientific community.”

Reference: www.ciriustx.com

Disclosure: Harrison reports he consults for and has received grant or research support from Cirius. Dittrich is the chief medical officer of Cirius Therapeutics.