Image. Recently, the therapeutic effect of GLP-1 class drugs for metabolic dysfunction-associated steatotic liver disease (MASH) is proven, and the development of new MASH drugs using GLP-1 is active. /Courtesy of Pixabay

The world's first treatment for metabolic dysfunction-associated steatotic liver disease (MASH) is generating sales that exceed market expectations, and as it prepares to expand into Europe following the United States, competition among corporations to develop a second new drug is intensifying. Various new drug candidates with different mechanisms of action are emerging in the MASH market, which is currently monopolized by a single product, including glucagon-like peptide-1 (GLP-1) class drugs that are fueling the obesity treatment trend.

According to the industry on the 27th, Madrigal Pharmaceuticals in the United States plans to launch 'Resmeta' (ingredient name: Resmetirom), approved as the world's first MASH treatment by the U.S. Food and Drug Administration (FDA) in March of last year, across Europe starting in Germany in the second half of this year. The company has applied to the European Medicines Agency (EMA) for marketing approval for Resmetirom and is awaiting a decision.

MASH was formerly known as nonalcoholic steatohepatitis (NASH) for some time, but to emphasize metabolic factors, the Global Liver Conference officially changed its name to MASH last year. Metabolism refers to the process by which the human body breaks down nutrients to obtain energy and eliminate waste products. MASH is a disease in which fat accumulates due to metabolic issues, accompanied by inflammation and liver damage, which can lead to cirrhosis and liver cancer, regardless of alcohol consumption.

Resmetirom is an oral medication in pill form that binds to the thyroid hormone receptor beta (THR-β), which regulates several metabolic processes in the body, enhancing liver fat metabolism, inflammation, and fibrosis processes. It was launched in the United States in April of last year and generated approximately $180 million (approximately 246.6 billion won) in sales over a span of about nine months. According to the financial information site Investing.com, the expected sales for Resmetirom this year are projected to reach $637 million (approximately 873 billion won).

With the expansion of the market for Resmetirom, competition surrounding the development of a second MASH new drug has intensified. The product that is expected to be released first is 'Wegovy' (semaglutide), an obesity treatment in the GLP-1 class developed by Danish company Novo Nordisk. Recently, Novo reported that 62.9% of patients in the Wegovy treatment group showed improvements in MASH symptoms without worsening liver fibrosis, and 37% showed improvements in liver fibrosis. The company plans to apply for FDA approval in the first half of this year based on these results.

Graphic = Jeong Seo-hee

Eli Lilly in the United States is also developing the obesity drug 'Mounjaro' (tirzepatide) as a treatment for MASH. Mounjaro is a dual-action agent that targets both GLP-1 and gastric inhibitory polypeptide (GIP), which promotes insulin secretion and has anti-inflammatory effects. It has currently completed phase 2 clinical trials, and the company is also developing three additional new drug candidates for MASH.

Domestic corporations are also ramping up efforts to develop MASH treatments using GLP-1. All of these have been designed to simultaneously activate GLP-1 and receptors with anti-inflammatory effects to enhance antifibrotic effects.

Hanmi Pharmaceutical is currently developing two MASH new drug candidates: 'Epinorpegtide,' a dual-action substance combining GLP-1 and glucagon (GCG) that was licensed to Merck (MSD) in the United States in 2020, and 'Eposipegtide,' a triple-action substance combining GLP-1, GCG, and GIP.

The company is conducting a joint phase 2b clinical trial comparing the efficacy of Epinorpegtide and Wegovy with MSD in the United States, and is expected to announce results by the end of this year. In the phase 2a trial analysis presented at the European Association for the Study of the Liver (EASL) in 2023, Wegovy reduced liver fat by 42.3%, whereas Epinorpegtide reduced it by 72.7%. The company is also conducting phase 2b trials for Eposipegtide, which is being developed in-house, in Korea and the United States.

D&D Pharmatech is also conducting phase 2 clinical trials in the United States for 'DD01,' a dual-action agent targeting GCG and GLP-1. It has been designated as a fast track for expedited review and approval by the FDA and is expected to announce main results of the 2nd phase in June.

Development of MASH new drugs in other classes is actively underway both domestically and internationally. The American company Akero Therapeutics is conducting phase 3 trials for the candidate substance 'Efruxifermin,' which targets fibroblast growth factor 21 (FGF21). FGF21 is a hormone secreted by the liver that lowers blood sugar and triglycerides while increasing energy metabolism, fat utilization, and lipid excretion. It is also effective in treating obesity and diabetes by inhibiting the growth of pancreatic beta cells and fat cells.

Yuhan Corporation has developed a new drug candidate 'BI 3006337' that targets both FGF21 and GLP-1 by combining the approaches of Akero and Novo Nordisk. The substance was exported to Boehringer Ingelheim in Germany in 2019, but was returned after development was halted in March. Yuhan Corporation is continuing to develop this substance as a MASH treatment.

Dong-A ST is conducting phase 2 clinical trials for 'DA-1241' through its U.S. subsidiary Metabio. DA-1241 targets GPR119, a receptor in pancreatic beta cells that, when activated, increases insulin secretion. On the 25th, the company announced that it has confirmed the liver fat improvement effects in the phase 2 trials.