After Rezdiffra (resmetirom) opened the door to the treatment of metabolic dysfunction-associated steatohepatitis (MASH), attention is focused on latecomer MASH drugs being developed by Korean companies.

As the market for MASH treatment gets in full swing, some experts expect that latecomer MASH drugs will not only deal with the existing indication of improving liver fibrosis but also promote combination therapy to control weight and blood sugar.

At the Bioplus-Interphex (BIX) Korea 2024 on Thursday, participants discussed the latest research trends, status, and prospects of MASH therapies under the theme, “Innovation and Investment Opportunities in MASH: A Multifaceted Approach.”

MASH is a disease characterized by the accumulation of triglycerides in liver cells regardless of alcohol consumption. It leads to inflammation and fibrosis in the liver, which can lead to serious liver diseases, including cirrhosis, liver cancer, and liver failure. The global prevalence of MASH is 2-4 percent and the prevalence in the United States is 3-5 percent.

It has been a disease with a large unmet need due to the lack of a cure. However, the market began to take shape in March this year when Madrigal Pharmaceuticals received the world's first approval from the U.S. Food and Drug Administration (FDA) for using Rezdiffra.

Hur Hye-min, an analyst at Kiwoom Securities, said that Rezdiffra's performance will have to be watched for the time being due to its high price and the relative lack of effectiveness as well as the fact that it takes about a year to build an industrial base but it remains highly valued.

"Madrigal's market capitalization is currently around 8.3 trillion won ($6.02 billion)," Hur said. "Rezdiffra has benefited from the prediction that it could become a blockbuster with annual sales of more than 1 trillion won by 2027, three years after its launch."

Hur predicted that the market for MASH therapies would gain more traction if the latecomers show momentum exceeding Rezdiffra.

"Gradually, more sophisticated data than the Madrigal products are coming out, so I expect that the latecomers will easily jump over the hurdle," Hur said. "There will be a lot of interesting data next year, and changes will occur this year by Hanmi Pharmaceutical and Dong-A ST so that MASH treatments will receive more attention next year.”

In Korea, Hanmi Pharmaceutical, Dong-A ST, D&D Pharmatech, Yuhan Corp., and Olix Pharmaceuticals are developing MASH treatments. The results of Hanmi Pharmaceutical's phase 2 trial of triple-agonist efocipegtrutide are expected in May next year, and Dong-A ST’s phase 2 trial of DA-1241 will likely be completed by the end of the year.

Hur also claimed that various combination therapies will emerge in the MASH treatment market.

"Combinations will be the mainstream in the future," she said. "Especially, data show that the combination of GLP-1 (glucagon-like peptide-1) and glucagon (GCG) has a greater effect on fatty liver than either product alone."

D&D Pharmatech CEO Lee Seul-ki said, "Most patients with MASH are accompanied by diabetes, and many obese patients usually have fatty liver." The company is developing DDo1, a GLP-1 and GCG dual agonist. "Now, there is a need for a drug with a complex mechanism that can not only improve liver fibrosis but also control blood sugar and control weight."

DD01 has been shown to inhibit fatty liver, improve blood sugar, and reduce weight in preclinical and phase 1 clinical trials. Last month, the company received the U.S. FDA’s approval for a global phase 2 clinical trial plan.

"The most important thing in MASH is glucagon, which is activated in the liver by itself but has no blood sugar or weight loss effect," Lee said. "For this reason, the activity of GLP-1, which plays a comprehensive role, is important, and we have been thinking about a dual agonist that maximizes the activity of GLP-1 while maintaining the activity of glucagon, and the result is the DD01 pipeline. "In the future, dual and triple combination therapies with GCG or GIP components will become the norm."