What Happened
The ESSENCE Study Group published interim results from a Phase 3, randomized, placebo-controlled trial testing once-weekly subcutaneous semaglutide (2.4 mg) in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced liver fibrosis (stage F2 or F3). The trial enrolled 1,197 participants in a 2:1 randomization to semaglutide or placebo, with a planned duration of 240 weeks. This interim analysis, published in the New England Journal of Medicine on June 5, 2025, reports results from the first 800 participants at week 72.
Why It Matters
This is the first large Phase 3 trial to report semaglutide's effect on liver biopsy outcomes in MASH specifically, rather than on weight or glycemic measures. It moves semaglutide's evidence base for a liver-specific indication from smaller Phase 2 data into a large, randomized, biopsy-confirmed Phase 3 setting -- a materially stronger form of evidence than the Phase 2 trials this compound was previously evaluated on for this indication.
What the Evidence Showed
At week 72 of this interim analysis, resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of participants on semaglutide versus 34.3% on placebo. A reduction in liver fibrosis stage without worsening of steatohepatitis occurred in 36.8% of the semaglutide group versus 22.4% on placebo. Both differences were reported as statistically significant by the trial authors.
What This Does Not Establish
This is a planned interim analysis on the first 800 of 1,197 enrolled participants at week 72 -- not the trial's final, full-cohort, 240-week readout, which has not yet been reported. The endpoints measured (steatohepatitis resolution and fibrosis stage on liver biopsy) are histologic surrogate outcomes, not hard clinical outcomes such as progression to cirrhosis, liver-related mortality, or transplant-free survival, which require much longer follow-up to assess. This trial evaluated MASH specifically; it does not establish or expand semaglutide's FDA-approved indications, which remain distinct from a MASH-specific approval. Results from one trial population do not by themselves establish durability of effect beyond the reported 72-week window.
Evidence Context
MitoCore's existing semaglutide evidence library is built primarily around its glycemic, weight-management, and cardiovascular-outcome trial data. This ESSENCE interim result extends that evidence into a new indication area (MASH/liver fibrosis) with a large, biopsy-confirmed Phase 3 design, but as an interim readout it does not by itself change any existing evidence grade for semaglutide's already-established indications. Given the scale and design quality of this trial, a future evidence-grade review specific to a liver/MASH-related claim may be warranted once final results are available.
Sources
1 source
- Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis
Clinical trial result