NAFLD(Non-Alcoholic fatty liver disease) & NASH (Non-alcoholic steatohepatitis)

Nonalcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. Recently, Dual agonist of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) are under clinical investigation for the treatment of obesity, type 2 diabetes, NAFLD. Severe NAFLD is accompanied by an inflammatory reaction and progresses to the NASH. The fat was accumulated in liver cause inflammation and damaged cells in the liver. NASH can get worse and cause scarring of the liver, which leads to cirrhosis. As to the cause of the onset, experts say that some people with fat deposits in the liver get NASH, while others do not know why. It is that something in the environment can cause inflammation in their people. Or maybe it's your family. There are no effective remedies developed so far, and medicines for improving liver function or drugs with efficacy for obesity are being prescribed.

[Market size]

There are currently no treatments for NASH and only clinical pipelines are being developed. According to Deutsche Bank, the NASH therapeutic market is expected to begin in 2019 and reach $ 32.1 billion by 2025.

The demand for NASH therapeutic products is increasing worldwide. In 2025, the NASH therapeutic market is expected to exceed $ 35 billion. NASH is currently in the desperate need to develop safe and effective therapeutic drugs because there are no world-market approved treatments. It is also necessary to develop a diagnostic method to replace the current liver biopsy for NASH diagnosis.

[Clinical trials & competitor]

As of February 28, 2018, 238 NASH clinical trials were found on clinicaltrials.gov/. In the case of chemical drug, Obeticholic acid(OCA, FXR agonist) is recruiting the patients for trials phase III. The GLP1 family of drugs, Liraglutide (Novo Nordisk), NASH clinical trials phase. In addition, many large pharmaceutical companies are conducting NASH studies for GLP1 and glucagon dual agonists, and have proven their effectiveness with various studies.

[Mode of Action]

Dual agonists of GLP1R and GCGR in the liver inhibit lipogenesis and promote lipolysis, inhibiting liver fat accumulation. In addition, GLP1 inhibits the expression of oxidative stress-related genes that induce NASH. Inhibition of hepatic lipid accumulation and oxidative stress through dual effects of GLP1 and GCGR is expected to have an improvement effect in NASH including NAFLD. According to journal of the report of hepatology research in 2016, the GLP1 family, Liraglutide, has been reported to reduce oxidative stress by enhancing weight loss, hepatic MDA reduction and mitochondrial architecture in severe NAFLD animal models.

[Reference]

1. "Liraglutide Ameliorates Non-Alcoholic Fatty Liver Disease By Enhancing Mitochondrial Architecture And Promoting Autophagy Through The SIRT1/SIRT3-Foxo3a Pathway".

2016. Hepatology Research 46 (9): 933-943. doi:10.1111/hepr.12634.

2. "Nonalcoholic Steatohepatitis (NASH) - Hepatic And Biliary Disorders - MSD Manual Professional Edition". 2018. MSD Manual Professional Edition.

http://www.msdmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/nonalcoholic-steatohepatitis-nash.

3. Patel, Vishal J, Amit Arvind Joharapurkar, Samadhan Kshirsagar, Maulik S Patel, Brijesh K Sutariya, Hiren M Patel, and Dheerendra Pandey et al. 2018.

"Co-agonist Of GLP-1 And Glucagon Receptors Ameliorates Non-Alcoholic Fatty Liver Disease" Canadian Journal Of Physiology And Pharmacology. doi:10.1139/cjpp-2017-0683.