Positive Gemcabene Results in Proof-of-Concept Preclinical NASH Study Presented at The Liver Meeting® 2017
Data Support Clinical Evaluation of Gemcabene as a Potential Treatment For NAFLD/NASH
Clinical Trial in NAFLD/NASH Planned to Begin 4Q-2017
In this study, gemcabene was evaluated in the STAM™ mouse model of NASH, in which diabetic mice fed a high fat diet rapidly develop fatty liver disease. Animals were treated with either gemcabene (at doses of 30, 100 and 300 mg/kg daily), a reference drug telmisartan (Micardis®, Boeringer Ingelheim) or vehicle. Key findings were as follows:
- At the highest dose level gemcabene-treated mice demonstrated a significant histological reduction in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS). Gemcabene also showed significant decreases in the fibrosis area at all doses compared to the vehicle group.
- Gene expression analysis showed that, in animals treated with 100 and 300 mg/kg gemcabene, there was a statistically significant decrease in mRNA expression levels of inflammation markers in the liver (TNF-α, MCP-1, MIP-1β, CCR5, CCR2, NF- κB), suggesting gemcabene hits multiple inflammatory targets and has a hepatoprotective effect on liver pathology.
- Genes related to stellate cell activation and collagen and fibrosis markers were down-regulated in this murine model of NASH.
“The effects of gemcabene on the liver histology and gene expression levels associated with inflammation revealed by this study are complementary to the results observed in dyslipidemia patients, and support our plans to move forward with the clinical evaluation of gemcabene in NAFLD/NASH,” said Dr.
About NAFLD/NASH
Nonalcoholic steatohepatitis (NASH) is a severe disease of the liver caused by hepatocyte inflammation and a buildup of fat in the organ. In the United States, NASH affects approximately 2-5% of the population. An additional 10-30% of Americans have fat in their liver, but no inflammation or liver damage, a condition called NAFLD or “fatty liver.” The underlying cause of NASH is unclear, but it most often occurs in persons who are middle-aged and overweight or obese. Many patients with NASH have elevated serum lipids, diabetes or pre-diabetes. Progression of NAFLD/NASH can lead to liver cirrhosis, fibrosis, hepatocellular carcinoma, liver failure and liver-related death. Liver transplantation is currently the only treatment for advanced cirrhosis with liver failure. At this time, there are no
Gemcabene’s mechanism of action and safety profile are highly differentiated from other clinical candidates
Gemphire’s product candidate gemcabene is a first-in-class, once-daily, oral therapy that may be suitable for patients who are unable to achieve normal levels of LDL-C or triglycerides with currently approved therapies, primarily statins. Gemcabene's mechanism of action (MOA) is designed to enhance the clearance of very low-density lipoproteins (VLDLs) in the plasma and inhibition of the production of cholesterol and triglycerides in the liver. The combined effect of these mechanisms has been clinically observed to result in a reduction of plasma non-HDL-C, VLDL-C, LDL-C, apolipoprotein B and triglycerides. In addition, gemcabene has been shown to markedly lower C-reactive protein in humans and improve insulin sensitization. Gemcabene’s MOA is liver-directed involving downregulation of hepatic apolipoprotein C-III (apoC-III) mRNA expression and decrease of plasma apoC-III levels. Gemcabene also reduces acetyl-CoA carboxylase (ACC1) and CCR2/CCR5 receptor mRNA levels, markers involved in the progression of non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD). Gemcabene has demonstrated proof of concept efficacy for NASH in the rodent STAM™ model developed at
About Gemphire
Gemphire is a clinical-stage biopharmaceutical company that is committed to helping patients with cardiometabolic disorders, including dyslipidemia and NASH. The Company is focused on providing new treatment options for cardiometabolic diseases through its complementary, convenient, cost-effective product candidate gemcabene as add-on to the standard of care, especially statins, that will benefit patients, physicians, and payors. Gemphire has initiated 3 clinical trials for homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH)/atherosclerotic cardiovascular disease (ASCVD), and severe hypertriglyceridemia (SHTG) under NCT02722408, NCT02634151, and NCT02944383, respectively, with a fourth planned trial in NASH to initiate in the fourth quarter of 2017. Please visit www.gemphire.com for more information.
Forward Looking Statements
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