Denifanstat MASH Trial Halves Cirrhosis Risk; Sagimet Eyes Phase 2 Combo, $122M Milestones
Sagimet’s Phase 2b MASH trial of denifanstat met both FDA-aligned endpoints, improving fibrosis without worsening disease and halving cirrhosis progression rates. Sagimet plans a Phase 2 cirrhotic qF4 trial combining denifanstat with resmetirom and is eligible for up to $122M milestones from its China acne NDA.
1. Phase 2b MASH trial results
Sagimet’s Phase 2b study of denifanstat achieved both primary endpoints aligned with FDA expectations: fibrosis improvement without worsening MASH and MASH resolution without worsening fibrosis. Digital pathology analyses corroborated human reads and showed patients on denifanstat were about half as likely to progress to cirrhosis compared with placebo.
2. Denifanstat-resmetirom combination strategy
The company plans a Phase 2 trial in cirrhotic qF4 patients testing multiple doses of denifanstat plus resmetirom against each component and placebo, with assessments at 52 and 96 weeks. Preclinical synergy data support complementary mechanisms—denifanstat blocks toxic fat synthesis while resmetirom oxidizes fat—and a Phase 1 PK/DDI study in ~40 volunteers confirmed tolerability.
3. China acne program and milestone potential
Partner Ascletis completed a Phase 3 trial of 50 mg denifanstat in moderate-to-severe acne, met all endpoints, and ran a 52-week extension showing sustained efficacy and safety. China’s NMPA accepted the NDA in December 2025, making Sagimet eligible for up to $122 million in development and commercial milestones plus tiered royalties.