Semaglutide analysis finds improved liver markers in leaner MASH subgroup

The subgroup analysis drew on the first 800 participants in ESSENCE’s 72-week interim analysis. Of those, 106 had a BMI below 27 kg/m². Novo Nordisk said results included improvements in the liver enzymes ALT and AST, the FAST score for disease activity, and the fibrosis markers ELF and PRO-C3. The vibration-controlled transient elastography liver stiffness measure (VCTE-LSM) also favored semaglutide, but its 95% confidence interval included 1.0.

Estimated treatment ratios were 0.61 for ALT (95% CI: 0.48–0.79), 0.67 for AST (0.56–0.80) and 0.82 for PRO-C3 (0.71–0.95). Estimated treatment differences were -0.13 for FAST (95% CI: -0.26 to -0.01) and -0.45 for ELF (-0.73 to -0.17). The VCTE-LSM ratio was 0.88 (0.73–1.06). The company said ratios below 1 and differences below 0 favor semaglutide.

Novo said the exploratory post hoc findings are hypothesis-generating and require further work to assess their clinical validity. They add to ESSENCE subgroup histology results for two endpoints: resolution of steatohepatitis without worsening fibrosis, and improvement in fibrosis without worsening steatohepatitis.

ESSENCE is an ongoing phase 3 trial of semaglutide 2.4 mg in adults with MASH and moderate-to-advanced fibrosis, stage F2 or F3. A total of 1,197 participants were randomized 2:1 to semaglutide or placebo, alongside standard care, for 240 weeks. The ongoing second part is assessing whether treatment lowers the risk of liver-related clinical events at 240 weeks. The analysis was presented by oral presentation at The Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases.