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Direct comparison study with GLP-1 agonist

Today, we would like to introduce a demonstration example of a drug efficacy evaluation test targeting GLP-1 using STAM^TM mouse.

Liraglutide, the first GLP-1 agonist in Japan, was launched on the market in 2010, and since then Exenatide, Lixisenatide, etc. have appeared. As of January 2024, Table 1 summarizes the clinical trials and non-clinical trials registered in Clinical Trials gov.

Table 1. Drug development status for NASH related to GLP-1

*1; Kojima M et al (Int J Mol Sci, 2020), *2; Mollerhoj MB et al (Clin Transl Sci, 2022), *3; Boland ML et al (Nat Metab, 2020), *4; Viking Therapeutics VK2735 – Viking Therapeutics, *5; Klein T et al (Med Mol Morphol, 2013), *6; Kawakubo M et al (Sci Rep, 2020), *7; Lee M et al (Sci Rep, 2020), *8; Lee SH et al (Biomed Pharmacother, 2023),*9, Bahirat UA et al (Eur J Pharmacol, 2017)

Drug development targeting GLP-1 continues to be active even today, and many news items related to GLP-1, such as those listed below, have been featured.

Pfizer suspends development of oral GLP-1 drug
Pfizer Announces Topline Phase 2b Results of Oral GLP-1R Agonist, Danuglipron, in Adults with Obesity | Pfizer

Semaglutide does not meet endpoint in NASH clinical trial
Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial – The Lancet Gastroenterology & Hepatology

Roche acquires Carmot, developer of GLP-1/GIP agonist
Carmot Therapeutics Enters into Definitive Merger Agreement with Roche | Carmot Therapeutics | Drug Discovery and Development

As listed in Table 1, STAM^TM mouse are a model that has a track record of evaluating drugs targeting GLP-1, such as Liraglutide, Linagliptin, DA-1241, and APD668. For example, a research group at Saga University School of Medicine has reported for the first time in the world that administering Linaglutide to STAM^TM mice suppresses NAFLD activity score, the progression of liver fibrosis, and hepatocarcinogenesis.
IJMS | Free Full-Text | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis (mdpi.com)

By using STAM^TM mouse, which have a track record of evaluating various drugs targeting GLP-1, it is possible to compare head-to-head with commercially available products such as Liraglutide, Linagliptin, and Sitagliptin, giving the developed product an advantage. It is possible to use this product to evaluate its potential as a therapeutic drug for MASH by comparing it with Semaglutide.

Although Semaglutide improved obesity in clinical studies, it did not show improvement in NASH or fibrosis, so the endpoint was not met. Therefore, it is thought that drug discovery targeting GLP-1 will continue to be actively conducted in the future. Are you interested in evaluating the efficacy of a test substance targeting GLP-1 using the STAM^TM mouse, a MASH/NASH model developed by our company for the first time in the world?