Metabolic Dysfunction-Associated Steatohepatitis (MASH)-Cirrhosis Clinical Trials: Lessons Learned and Future Directions - PubMed
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- #MASH-cirrhosis
- MASH-cirrhosis is a growing global health concern due to risks of hepatic decompensation, HCC, and liver-related mortality.
- Phase 3 trials for compensated MASH-cirrhosis use composite endpoints like MALO (hepatic decompensation, liver transplantation, all-cause mortality).
- Future trials should focus on high-risk patients (CSPH, Child Turcotte Pugh A cirrhosis, MRE > 6.5 kPa) with 3-5 years follow-up.
- Accelerated approval may be possible based on histologic reversal of cirrhosis, as seen in the SYMMETRY Phase 2b trial with efruxifermin.
- Key levers to increase cirrhosis regression include liver stiffness limits, platelet thresholds, and prespecified fibrosis markers.
- Ongoing studies include survodutide (glucagon/GLP-1 agonist), efruxifermin (FGF21 analog), and resmetirom (thyroid hormone receptor β agonist).
- Authors disclose extensive industry funding, consulting, and advisory roles in pharmaceutical companies.