Simtuzumab may not yield improvements in fibrosis in nonalcoholic steatohepatitis
Treatment with simtuzumab does not appear to induce significant reductions in nonalcoholic steatohepatitis (NASH)-related fibrosis or cirrhosis, according to the results of a phase 2b trial.
A total of 219 patients with bridging fibrosis caused by NASH were randomly assigned to groups given weekly subcutaneous injections of simtuzumab at either 75 or 125 mg, or placebo (n=75 per group) for a planned duration of 240 weeks. A separate cohort of 258 patients with compensated cirrhosis were also randomized to receive intravenous simtuzumab at either 200 or 700 mg, or placebo (n=86 per group) every other week. Biopsies were collected and analysed at baseline and at weeks 48 and 96.
The study was terminated after 96 weeks due to lack of efficacy. The primary endpoint of hepatic collagen content (assessed by morphometry of liver specimens) in the fibrosis cohort significantly dropped from baseline, although the changes did not differ among the three treatment groups (75 mg simtuzumab vs placebo: difference, −0.2 percent; p=0.77; 125 mg vs placebo; difference, −0.4 percent; p=0.52).
In the cirrhosis cohort, no significant improvements were seen in the main outcome of hepatic venous pressure gradient at week 96 (200 and 700 mg simtuzumab vs placebo: difference, 0.1 mg for both comparisons; p=0.84 and p=0.88, respectively).
Finally, simtuzumab did not reduce fibrosis stage, slow progression to cirrhosis in patients with bridging fibrosis, or prevent liver-related clinical events in patients with cirrhosis. Adverse events occurred at similar rates among treatment groups.