SAN DIEGO and KALAMAZOO, Mich., June 15, 2020 /PRNewswire/ -- Cirius Therapeutics, a clinical-stage pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and metabolic diseases, today announced the presentation of clinical data at the virtual American Diabetes Association's (ADA) 80th Scientific Sessions showing that patients treated with MSDC-0602K, its therapeutic candidate currently under development for NASH, demonstrated improvements in insulin sensitization and insulin clearance compared to those treated with placebo.
Poor insulin handling is a root cause of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH) and Type 2 diabetes (T2D). High levels of fasting plasma insulin (FPI) have been shown to be a predictor of poor cardiovascular outcomes in patients with T2D.
In the study presented at ADA, entitled 'MSDC-0602K, A New Oral Insulin Sensitizer In Insulin Resistant Nash Patients With And Without Type 2 Diabetes (T2D),' researchers analyzed the changes in markers associated with poor glycemic control in participants from Cirius' Phase 2b EMMINENCE clinical trial, all of whom were biopsy-confirmed to have NASH. The results presented showed that participants enrolled in the trial had elevated baseline FPI levels that averaged 22-29 mU/ml across the four treatment groups, more than twice normal fasting insulin levels. During the course of the trial, FPI levels continued to increase in participants receiving placebo, while those treated with MSDC-0602K showed statistically significant improvements in FPI. After twelve months of treatment, two MSDC-0602K treatment groups (125 mg and 250 mg) demonstrated an average reduction in FPI of 30%. In contrast, the placebo group showed a 9% increase in FPI.
In addition, patients showed statistically significant improvements in insulin clearance, estimated by the ratio of C peptide to FPI, compared to placebo. These results, which accompanied improved glycemic control in MSDC-0602K-treated patients, suggest both a reduction in insulin secretion and an increase in liver clearance of insulin.
"People who have comorbid NAFLD/NASH and diabetes may suffer from reduced insulin clearance in addition to insulin resistance, and this may contribute to persistently high levels of the circulating hormone," said Stephen Harrison, M.D., a principal investigator on the EMMINENCE trial and member of Cirius' scientific advisory board. "Given that cardiovascular disease is the major source of morbidity and mortality in people with NAFLD/NASH and that elevated levels of fasting insulin are associated with negative cardiovascular health, the improvements in insulin handling measured in the EMMINENCE trial show that MSDC-0602K may offer strong potential benefit to the NASH and Type 2 diabetes communities."
In another presentation entitled 'The New Insulin Sensitizer MSDC-0602K Synergizes with the GLP-1 Receptor Agonist Liraglutide,' Dr. Kyle McCommis from the St. Louis University School of Medicine presented data from a mouse model of diabetes which showed that MSDC-0602K improved glycemic control, lowered plasma insulin and increased the insulin content of pancreatic islets. When added together with the GLP-1 agonist liraglutide, the combination treatment further improved glucose tolerance without elevation of fasting insulin and with a further increase in pancreatic insulin content.
According to Jerry Colca, Ph.D., chief scientific officer of Cirius Therapeutics, "These studies show the potential of MSDC-0602K to improve insulin handling and to preserve pancreatic islet function, important aspects of metabolic pathology that are not fully addressed by current treatments."
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. Its lead product candidate, MSDC-0602K, is a novel small molecule being developed as a once-daily oral therapy to treat NASH. 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.