The following is a summary of the “Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH ,” published in the March 2023 issue of Gastroenterology by Ratziu et al.
Vonafexor is a second-generation, non-bile acid farnesoid X receptor agonist, and the LIVIFY trial looked into its safety, tolerability, and efficacy in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH). There were 2 parts to this phase IIa double-blind trial. First, patients were randomized (1:1:1:1) to receive a placebo, vonafexor 100 mg twice daily (VONA-100BID), vonafexor 200 mg once daily (VONA-200QD), or 400 mg vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B. Primary effectiveness outcome was a change from baseline to Week 12 in liver fat content (LFC) as measured by MRI proton density fat fraction. Secondary endpoints included changes from baseline to Week 12 in corrected T1 values and liver enzymes.
About 120 patients (24 in Part A and 96 in Part B) were randomly assigned. Between Weeks 0 and 12 of the Part B study, the least-squares mean (SE) absolute change in LFC was significantly lower for both VONA-100QD (-6.3% [0.9]) and VONA-200QD (-5.4% [0.9]) than for placebo (-2.3% [0.9], P = 0.002 and 0.012, respectively). Compared to the placebo group, 50% of patients on VONA-100QD and 39.3% of patients on VONA-200QD were able to reduce their relative LFC by >30%. As a bonus, vonafexor decreased both body weight and liver enzymes and corrected T1.
The glomerular filtration rate, as measured by creatinine, increased in the treatment arms but not in the placebo group. About 6.3%, 9.7%, and 18.2% of patients in the placebo, VONA-100QD, and VONA-200QD arms had mild to moderate generalized pruritus. Vonafexor was well tolerated and led to significant reductions in liver fat and liver enzymes as well as weight loss and a potential benefit for the kidneys in patients with probable fibrotic NASH.
Source: sciencedirect.com/science/article/pii/S0168827822031609