Gilead Sciences and Novo Nordisk have expanded their clinical collaboration in non-alcoholic steatohepatitis (NASH).
The companies will conduct a phase 2b double-blind, placebo-controlled study to investigate the safety and efficacy of Novo Nordisk’s semaglutide, a GLP-1 receptor agonist, and a fixed-dose combination of Gilead’s investigational FXR agonist cilofexor and investigational ACC inhibitor firsocostat, alone and in combination in people with compensated cirrhosis (F4) due to NASH. The four-arm study in approximately 440 patients will evaluate the treatments’ impact on liver fibrosis improvement and NASH resolution and will begin recruitment in the second half of 2021.
“NASH is a disease with a high unmet medical need, as no drugs are currently approved to treat this potentially life-threatening condition. Building on the positive results from our proof-of-concept trial, we hope together with Gilead to demonstrate the potential for semaglutide with cilofexor and firsocostat to help people living with NASH,” says Martin Holst Lange, executive vice president and head of Development at Novo Nordisk.
Built on positive results from a phase 2a proof-of-concept study
This new phase 2b study builds on positive results from a phase 2a proof-of-concept study presented at the Liver Meeting Digital Experience in November 2020 investigating semaglutide alone and in combination with cilofexor and/or firsocostat in 108 people with NASH, and mild to moderate fibrosis. The study met its primary endpoint, demonstrating that all regimens were well tolerated over 24 weeks. The most common adverse events were gastrointestinal. Across all groups, 5–14% of people discontinued any trial treatment due to adverse events.
In addition, post-hoc analyses of exploratory efficacy endpoints assessing biomarkers of liver health at 24 weeks showed statistically significant improvements in hepatic steatosis (measured by magnetic resonance imaging proton density fat fraction; MRI-PDFF) and liver injury (measured by serum alanine aminotransferase; ALT) in the combination treatment arms versus semaglutide alone. Liver stiffness and the Enhanced Liver Fibrosis (ELF) score declined in all groups; however, statistically significant differences between groups were not observed.
Cilofexor and firsocostat are investigational compounds and are not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory authority. Their safety and efficacy have not been established. Semaglutide has not been approved by the FDA or any other regulatory authority for the treatment of patients living with NASH but has been approved for the treatment of type 2 diabetes.
Photo of Martin Holst Lange, Executive vice president, head of Development: Novo Nordisk