Data from a phase 2 randomized, placebo-controlled trial of the investigational, selective, non-steroidal farnesoid X receptor ( FXR ) agonist GS-9674 were presented at The Liver Meeting 2018 in San Francisco.
In this study, 140 NASH ( nonalcoholic steatohepatitis ) patients were treated with GS-9674 100 mg, GS-9674 30 mg or placebo orally once daily for 24 weeks.
A decline of at least 30% in hepatic fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF ) was observed in 38.9% of patients treated with GS-9674 100 mg ( p=0.011 vs placebo ), 14% treated with GS-9674 30 mg ( p=0.87 ), and 12.5% with placebo.
Improvements in liver biochemistry tests ( serum GGT ) and markers of reduced bile acid synthesis ( serum C4 and bile acids ) were observed in the 30 mg and 100 mg arms of GS-9674-treated patients.
GS-9674 was generally well tolerated; moderate to severe pruritus, or itching, occurred in 14% of patients in the GS-9674 100 mg arm compared to 4% in the GS-9674 30 mg and placebo arms. Changes in lipid profile and glycemic parameters did not differ between GS-9674 and placebo-treated patients.
The most common adverse events in patients treated with GS-9674 were pruritus, upper respiratory tract infection, headache and fatigue.
Treatment was discontinued due to adverse events in one patient treated with GS-9674 100 mg ( 2% ), five patients treated with GS-9674 30 mg ( 9% ), and two patients with placebo ( 7% ). ( Xagena )
Source: Gilead, 2018