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New advances in novel pharmacotherapeutic candidates for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) between 2022 and 2024

Acta Pharmacologica Sinica volume 46, pages 1145–1155 (2025)Cite this article

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a broad spectrum of profile from simple fatty liver, evolving to metabolic dysfunction-associated steatohepatitis (MASH), to hepatic fibrosis, further progressing to cirrhosis and hepatocellular carcinoma (HCC). MASLD has become a prevalent disease with 25% in average over the world. MASH is an active stage, and requires pharmacological intervention when there is necroptotic damage with fibrotic progression. Although there is an increased understanding of MASH pathogenesis and newly approved resmetirom, given its complexity and heterogeneous pathophysiology, there is a strong necessity to develop more drug candidates with better therapeutic efficacy and well-tolerated safety profile. With an increased list of pharmaceutical candidates in the pipeline, it is anticipated to witness successful approval of more potential candidates in this fast-evolving field, thereby offering different categories of medications for selective patient populations. In this review, we update the advances in MASH pharmacotherapeutics that have completed phase II or III clinical trials with potential application in clinical practice during the latest 2 years, focusing on effectiveness and safety issues. The overview of fast-evolving status of pharmacotherapeutic candidates for MASH treatment confers deep insights into the key issues, such as molecular targets, endpoint selection and validation, clinical trial design and execution, interaction with drug administration authority, real-world data feedback and further adjustment in clinical application.

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Fig. 1: A schematic illustration of the major modes of the potential pharmaceutical candidates in MASH or MASLD.

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Acknowledgements

The work is supported partially by the National Natural Science Foundation of China (NSFC #82370625, 82170624).

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  1. These authors contributed equally: Shu Wei Wong, Yong-yu Yang

Authors and Affiliations

  1. Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China

    Shu Wei Wong, Yong-yu Yang, Hui Chen, Li Xie & Jian Wu

  2. Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China

    Xi-zhong Shen, Ning-ping Zhang & Jian Wu

  3. Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China

    Xi-zhong Shen, Ning-ping Zhang & Jian Wu

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  1. Shu Wei Wong
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  4. Li Xie
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Wong, S.W., Yang, Yy., Chen, H. et al. New advances in novel pharmacotherapeutic candidates for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) between 2022 and 2024. Acta Pharmacol Sin 46, 1145–1155 (2025). https://doi.org/10.1038/s41401-024-01466-7

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