Trial results for a Phase 2 study (NCT04971785) investigating semaglutide in combination with cilofexor/firsocostat for adults with cirrhosis due to Nonalcoholic Steatohepatitis (NASH) were posted on ClinicalTrials.gov on 2025-11-26. The study found that 57.3% of participants receiving the semaglutide + cilofexor/firsocostat fixed-dose combination (FDC) achieved NASH resolution without worsening fibrosis, a statistically significant improvement compared to control groups.
Background
The clinical study aimed to evaluate whether the combination of semaglutide (SEMA) and the fixed-dose combination of cilofexor/firsocostat (CILO/FIR FDC) could lead to fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants diagnosed with cirrhosis due to NASH.
Trial design
The study (NCT04971785) was a Phase 2 trial that enrolled 457 participants. It investigated semaglutide, cilofexor/firsocostat, alone and in combination, in adults with Nonalcoholic Steatohepatitis. Interventions included semaglutide (sema), cilofexor (cilo)/firsocostat (fir), ptm sema, and ptm cilo/fir.
Key results
The trial reported key measurements and analyses for fibrosis improvement and NASH resolution at Week 72.
For the outcome of "Percentage of Participants Who Achieved ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 72":
- Participants in the SEMA + CILO/FIR FDC group achieved 13.7%.
- Participants in the PTM SEMA + PTM CILO/FIR group achieved 8.3%.
A stratified Mantel-Haenszel test comparing these groups showed a difference of 5.7% (95% Confidence Interval: -3.6 to 14.9) with a p-value of 0.2289.
- When comparing SEMA + CILO/FIR FDC (13.7%) to SEMA + PTM CILO/FIR (15.6%), the difference was -1.8% (95% Confidence Interval: -11.1 to 7.4) with a p-value of 0.6959.
For the outcome of "Percentage of Participants With NASH Resolution Without Worsening in Fibrosis at Week 72":
- Participants in the SEMA + CILO/FIR FDC group achieved 57.3%.
- Participants in the PTM SEMA + PTM CILO/FIR group achieved 22.4%.
A stratified Mantel-Haenszel test comparing these groups showed a statistically significant difference of 35.7% (95% Confidence Interval: 18.8 to 52.6) with a p-value of 0.0001.
- When comparing SEMA + CILO/FIR FDC (57.3%) to PTM SEMA + CILO/FIR FDC (31.8%), the difference was 26.1% (95% Confidence Interval: 11.3 to 40.9) with a p-value of 0.0006.
What this means
The results indicate that the combination of semaglutide with cilofexor/firsocostat significantly improved NASH resolution without worsening fibrosis in patients with cirrhosis due to NASH. While fibrosis improvement did not reach statistical significance in the primary comparison, the strong effect on NASH resolution suggests a potential therapeutic benefit for this challenging condition.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04971785, titled "Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NAS," were posted on 2025-11-26 on clinicaltrials.gov.