Semaglutide plus cilofexor, firsocostat well tolerated in NASH-related fibrosis

Treatment with semaglutide with firsocostat and/or cilofexor is well tolerated in patients with mild-to-moderate fibrosis due to nonalcoholic steatohepatitis (NASH), a study has shown.

Moreover, exploratory efficacy analyses revealed that the above treatment provided additional improvements in liver steatosis and biochemistry compared with semaglutide alone.

A team of investigators conducted a phase II, open-label, proof-of-concept trial in patients with NASH (F2‒F3 on biopsy, or magnetic resonance imaging-proton density fat fraction [MRI-PDFF] ≥10 percent and liver stiffness by transient elastography ≥7 kPa).

Participants were randomly assigned to receive 24 weeks’ treatment with semaglutide 2.4 mg once weekly as monotherapy or combined with once-daily cilofexor (30 or 200 mg) and/or once-daily firsocostat 20 mg. Safety was the primary endpoint. All efficacy endpoints were exploratory.

Of the 108 randomized patients, 21 received semaglutide alone, 22 semaglutide plus cilofexor 30 mg, 22 semaglutide plus cilofexor 100 mg, 22 semaglutide plus firsocostat, and 21 segmalutide plus cilofexor 30 mg and firsocostat.

All treatment regimens were well tolerated, with similar incidence of adverse events across groups (73‒90 percent). Majority of these events were gastrointestinal in nature.

Weight loss was also comparable across groups (7‒10 percent), but combination treatments led to greater improvements in liver steatosis measured by MRI-PDFF (least-squares mean of absolute changes, ‒9.8 to ‒11.0 vs ‒8.0 percent), liver biochemistry, and noninvasive tests of fibrosis compared with semaglutide monotherapy.

“Given this was a small-scale open-label trial, double-blind placebo-controlled trials with adequate patient numbers are warranted to assess the efficacy and safety of these combinations in NASH,” the investigators said.