From June 5 to 8, 2024, the European Association for the Study of the Liver (EASL) Annual Meeting was held in Milan, Italy. This major event brought together over 7,000 professionals, including clinicians, researchers, healthcare workers, patient representatives, and industry experts. During the conference, Professor Jian Gao Fan from the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine presented a poster titled “ASC41, a selective THR-β agonist significantly reduces liver fat and ALT in biopsy-confirmed MASH patients after 12-week treatment: an interim analysis of a 52-week serial liver biopsy study,” which attracted considerable attention. Professor Fan shared with us the main findings and clinical significance of this research.Background and Objectives
Metabolic associated fatty liver disease (MAFLD), formerly known as NAFLD, is a chronic liver disease characterized by excessive fat accumulation in hepatocytes, excluding damage caused by alcohol and other known liver damage factors. Currently, 25% of the global adult population has MAFLD. In China, it is estimated that 173 million to 310 million people have MAFLD. MAFLD has surpassed viral hepatitis and alcoholic liver disease to become the most common liver disease. In March 2024, Resmetirom received accelerated approval from the U.S. FDA for use in combination with diet and exercise to treat metabolic dysfunction-associated steatohepatitis (MASH), marking the first FDA-approved innovative drug for MASH, bringing significant attention to the THR target in the industry.
ASC41, developed using proprietary formulation technology by a domestic pharmaceutical company, is a highly selective THR-β agonist with liver targeting properties, currently leading in clinical trial progress among similar drugs.
Research Methods
We are conducting a phase II clinical trial of ASC41, expected to enroll approximately 180 biopsy-confirmed MASH patients. Participants are randomly assigned in a 1:1:1 ratio to two ASC41 treatment groups (2 mg or 4 mg, QD) and a placebo control group, treated for 52 weeks with a 4-week follow-up. This report presents the interim analysis results of 42 patients who have completed 12 weeks of treatment with ASC41 or placebo.
Results
The analysis found that after 12 weeks of ASC41 treatment, the relative reduction in liver fat content from baseline was as high as 68.2%, with 93.3% of patients showing a relative reduction in liver fat content of ≥30% from baseline. Additionally, ALT and AST levels showed relative reductions from baseline of 32.6% and 24.2%, respectively, with 73.3% of patients experiencing a decrease in ALT of >17 U/L, which is associated with histological response in MASH patients. LDL-C, total cholesterol (TC), and triglycerides (TG) levels showed relative reductions from baseline of 23.4%, 20.0%, and 42.6%, respectively.
Moreover, ASC41 demonstrated good safety and tolerability. Most adverse events in all cohorts (including the placebo cohort) were grade 1.
When comparing baseline characteristics with those of Resmetirom and VK-2809 phase II clinical trials, ASC41 subjects had similar characteristics. In this interim analysis, ASC41 significantly reduced liver function markers ALT and AST, while Resmetirom and VK-2809 did not show statistically significant differences in ALT and AST compared to placebo at week 12. These data suggest that ASC41 is distinct from other THR-β agonists.
Conclusion
We are very pleased to have obtained positive interim results in this phase II clinical trial of ASC41 in biopsy-confirmed MASH patients. We look forward to the positive results of the entire study, hoping to bring innovative drugs to many Chinese MASH patients as soon as possible.
Expert Profile
Professor Jian Gao Fan
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
- Chairman of the Digestive Disease Branch of the Shanghai Medical Association
- Member of the Standing Committee of the Liver Disease Branch of the Chinese Medical Association
- Deputy Chairman of the Liver Disease Branch of the Shanghai Medical Association
Main Research Interests:
- Mechanisms and treatment of liver fibrosis
- Metabolic liver diseases
- Viral hepatitis
Publications:
- Published over 100 papers in peer-reviewed journals, including Hepatology and Journal of Hepatology
- Principal investigator of several national and international clinical trials
