Gilead, Novo Nordisk insights from mid-stage trial of triple combo in NASH

• Gilead Sciences (NASDAQ:GILD) and Novo Nordisk (NYSE:NVO) presents results from a Phase 2 proof-of-concept trial. The five-arm trial evaluated combinations of Novo Nordisk’s semaglutide, a GLP-1 receptor agonist, with Gilead’s investigational FXR agonist cilofexor and/or ACC inhibitor firsocostat over 24 weeks in 108 people with non-alcoholic steatohepatitis (NASH), at The Liver Meeting Digital Experience (TLMdX), November 13–16, 2020.
• The trial met its primary endpoint by demonstrating that in people with NASH and mild to moderate fibrosis all regimens were well tolerated.
• The most common adverse events (AEs) were gastrointestinal. Minimal pruritus (itching) was observed in people treated with cilofexor. 5–14% of people discontinued any trial treatment.
• Exploratory efficacy endpoints assessing biomarkers of liver health at 24 weeks showed statistically significant improvements in hepatic steatosis and liver injury in the combination arms versus semaglutide alone.
• Although liver stiffness declined in all groups, statistically significant differences were not observed.
• The companies are also presenting preclinical data supporting the development of combination approaches in NASH.
• In the preclinical trial, semaglutide alone and in combination with cilofexor and/or GS-834356 (an analog of firsocostat) were administered daily for 12 weeks in a murine model of diet-induced NASH (n=15-16/group).
• The results demonstrated that while semaglutide significantly improved NASH and fibrosis-related endpoints, the addition of either cilofexor or the firsocostat analog further improved liver fat reduction. The combination of all three agents had the greatest impact on changes in the NAFLD Activity Score.
• The safety and efficacy of firsocostat, GS-834356 and cilofexor have not been established.
• https://seekingalpha.com/news/3636417-gilead-novo-nordisk-provide-insights-from-mid-stage-trial-describing-triple-combo-regimen-in