Pegozafermin shows promise in NASH patients

In the treatment of patients with nonalcoholic steatohepatitis (NASH), the glycoPEGylated FGF21 analogue pegozafermin appears to confer beneficial effects on hepatic and metabolic parameters while being well tolerated, according to the results of a phase 1b/2a clinical trial.

Conducted at 16 centres in the US, the trial enrolled 20 adult patients (mean age 58.4 years, 75 percent women, 100 percent White, mean body mass index 37.0 kg/m²) with NASH (stage 2 or 3 fibrosis, NAS ≥4) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) ≥8 percent. These patients were given subcutaneous pegozafermin 27 mg once weekly for 20 weeks.

Of the patients, 19 completed the study. The primary endpoint of ≥2-point improvement in NAFLD activity score with ≥1-point improvement in ballooning or lobular inflammation and no worsening of fibrosis was documented in 12 patients (63 percent).

Twenty-six percent of patients showed an improvement in fibrosis without worsening of NASH, whereas 32 percent achieved NASH resolution without worsening of fibrosis.

At week 20, MRI-PDFF decreased from baseline by −64.7 percent (95 percent confidence interval [CI], 71.7 to −57.7; p<0.0001). There also were significant improvements observed in serum aminotransferases, noninvasive fibrosis tests, serum lipids, glycaemic control, and body weight.

In terms of safety, 18 patients (90 percent) experienced adverse events (AEs). The most frequently reported AEs were mild-to-moderate nausea and diarrhoea. None of the patients had serious AEs, discontinued treatment due to AEs, or died.