MASH represents a therapeutic area with an exceptionally large patient population, a clear regulatory pathway for drug approval, yet currently very low drug penetration. The disease exhibits significant heterogeneity, making it difficult for single-target therapies to address the full spectrum of the disease process. The stronger-than-expected sales of Resmetirom have validated the genuine payment capacity of the MASH market, suggesting that multinational corporations are likely to further expand their strategic focus around MASH assets, with opportunities for differentiated assets to expand globally. The key viewpoints from GTHT are as follows:

Market Potential for MASH

MASH is a serious, progressive liver disease closely linked to metabolic conditions such as obesity, type II diabetes, and cardiovascular disease. The global MASH patient population is projected to grow to 533 million by 2034. Without timely intervention, MASH can progress to cirrhosis, defining it as a chronic disease market with a clear disease burden and significant intervention value. Currently, only two drugs are approved in this space: Resmetirom (THR-β) and Semaglutide (GLP-1R). As the first drug approved for MASH, Resmetirom achieved sales of $960 million in its first full sales year in 2025. However, as of Q1 2026, only 42,250 patients were receiving treatment. With anticipated improvements in diagnosis rates from non-invasive testing methods, expansion into the F4 patient population, and the launch of more effective new drugs, there is substantial room for growth in MASH drug market penetration.

Scarcity of Viable MASH Assets

The high degree of disease heterogeneity presents a major challenge, as single-target approaches have historically struggled to simultaneously address metabolic dysfunction, inflammation, and fibrosis. From a clinical development perspective, the barriers are high: preclinical research is difficult, animal models do not perfectly mirror human disease, and clinical trials relying on liver biopsy as a hard endpoint face challenges with slow patient enrollment, long trial durations, and high difficulty in observing and achieving endpoints. Consequently, the number of drug candidates in mid-to-late-stage development remains limited.

Identifying Assets with Differentiated Advantages

Key competitive advantages include efficacy in improving fibrosis endpoints, enhanced dosing convenience, and a strong safety profile. Companies like Madrigal, following the success of Resmetirom, are actively acquiring assets targeting GLP-1, small nucleic acids, and DGAT2, indicating that combination therapy may become the mainstream treatment trend for MASH in the future. Furthermore, as a crucial extension within the cardio-renal-metabolic (CVRM) field, MASH is poised to become a key strategic focus for multinational corporations in the post-GLP-1 era. The core strengths of drugs targeting different pathways are becoming clear: GLP-1-based drugs show outstanding efficacy in MASH resolution, focusing on weight and metabolic improvements; THR-β agonists, while showing relatively weaker efficacy on the two hard endpoints, offer good liver fat reduction benefits and the convenience of oral administration, positioning them as potential foundational therapies; FGF21 analogs directly target anti-fibrotic pathways with strong evidence in populations with severe fibrosis and cirrhosis; and oral pan-PDE small molecules combine the convenience of oral dosing with promising anti-fibrotic potential, highlighting a clear differentiated advantage.

Recommended Focus

Zhong Sheng Yao Ye's ZSP1601 (pan-PDE) is recommended for its strong anti-fibrotic evidence, oral convenience, and leading clinical progress. In May 2026, the company announced positive top-line data from its Phase IIb trial. The results showed that the 48-week paired biopsy composite endpoint was significantly superior to placebo, with fibrosis improvement ≥1 stage without worsening of MASH, and fibrosis improvement ≥2 stages without worsening of MASH. The placebo-adjusted rate differences were 29.50% and 10.60%, respectively. The drug demonstrated excellent oral safety, and its anti-fibrotic capability is comparable to injectable formulations in the FGF21 class. Other companies to watch include Hai Si Ke, Hua Dong Yi Yao, and Rui Bo Sheng Wu.

Investment risks include potential delays in research and development, intensifying competition, and challenges in achieving successful commercialization and widespread adoption in clinical practice.