Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide.  The disease affects 90% of morbidly obese individuals and often clusters with prediabetes or overt type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD and a leading cause of end-stage liver disease and indication for liver transplantation. The conditions is associated with excess flow of free fatty acids and fat deposition in various organs. Insulin resistance and obesity are considered contributing and risk factors, suggesting effective blood glucose control as a means of preventing and managing NAFLD. ORMD-0801 is an oral insulin formulation designed to enable portal delivery and first-pass metabolism of the active ingredient. By mimicking the physiological path taken by pancreatic insulin, it is expected to have a distinct effect on the hepatic aspect of carbohydrate metabolism and insulin resistance. In a double-blind, randomized, placebo-controlled, multicenter study, patients with NASH and T2DM were treated twice daily for 12 weeks with an 8 mg insulin (n=21) or placebo (n=11) capsule. Liver fat content and liver fibrosis and steatosis levels were measured at baseline and at the end of treatment, by MRI-PDFF by FibroScan®, respectively. Twelve weeks of active treatment led to a -11.2±22.8% and -11.7±21.1% reduction in whole-liver and segment 3 fat content, respectively, while placebo brought to a -6.5±15.3% and +0.1±17.3% in these  parameters. ORMD-0801 induced a median -1.1 kPa and -21.0 dB/m reduction in fibrosis and steatosis levels, respectively, while placebo treatment led to increases of 0.3 kPa and 13.0 dB/m, respectively. In parallel, HbA1c levels declined by -0.27±1.3% in the active arm and increased by 0.23±0.73 in the placebo arm. No severe drug-related adverse events were reported. Future studies will further assess the potential of ORMD-0801 to reduce progression to end-stage liver disease and need for liver transplantation.

Dr. Miriam Kidron serves as Oramed's Chief Scientific Officer and Director since the company's establishment. She has overseen all of Oramed's preclinical and clinical studies performed to date.  As a pharmacologist and biochemist, Kidron earned her PhD in biochemistry from the Hebrew University of Jerusalem. For close to 20 years, Dr. Kidron has been a senior researcher in the Diabetes Unit at Hadassah-Hebrew University Medical Center in Jerusalem, Israel, earning the Bern Schlanger Award for her work on diabetes research. She was formerly a visiting professor at the Medical School at the University of Toronto and is a member of the American and Israeli Diabetes Associations.