1. In this randomized controlled trial, treatment with pegozafermin improved fibrosis in patients with nonalcoholic steatohepatitis (NASH).
2. Treatment with pegozafermin led to increased rates of NASH resolution.
Evidence Rating Level: 1 (Excellent)
Study Rundown: NASH is a disease characterized by hepatic inflammation and excess fat accumulation with or without fibrosis of the liver. Pegozafermin is a long-acting recombinant fibroblast growth factor 21 analog pegylated with the use of site-specific glycosyltransferases. It is currently being developed for the treatment of NASH and severe hypertriglyceridemia. However, there is a gap in knowledge as to understanding whether pegozafermin therapy improves hepatic steatosis, markers of inflammation, hepatic fibrosis, circulating lipid levels, or glycemic control. Overall, this study found that pegozafermin treatment for 24 weeks led to improvements in fibrosis with both weekly and every two-week administration in patients with biopsy-confirmed NASH. This study was limited by its short duration and with lack of racial diversity as most of the study patients were White which can limit generalizability. Nevertheless, these study’s findings are significant, as they demonstrate that pegozafermin may be effective in improving fibrosis in patients with NASH.
In-Depth [randomized controlled trial]: This phase double-blinded, randomized, placebo-controlled trial studied 22 patients with biopsy-confirmed NASH. Patients who were 21 to 75 years of age and had NASH as confirmed on a biopsy no more than six months before screening were eligible for the study. Patients who had liver disease other than NASH, cirrhosis, uncontrolled or newly diagnosed diabetes, or any illness that might affect the results of the trial were excluded from the trial. The primary outcomes measured were an improvement (reduction) in fibrosis of at least one stage, without worsening of NASH (defined as an increase in ballooning, inflammation, or steatosis), and NASH resolution (defined as the total absence of ballooning and absence or mild inflammation) without worsening of fibrosis (an increase of ≥1 stage). Based on the primary analysis, 7% in the pooled placebo group, 22% in the 15mg pegozafermin group (difference versus placebo, 14%; 95% Confidence Interval [CI], −9 to 38), 26% in the 30mg pegozafermin group (difference, 19%; 95% CI, 5 to 32; p=0.009), and 27% in the 44mg pegozafermin group (difference, 20%; 95% CI, 5 to 35) showed significant improvement in fibrosis. For patients who met the criteria for NASH resolution, the following percentages were reported: 2% in the placebo group, 37% in the 15mg pegozafermin group (difference vs. placebo, 35%; 95% CI, 10 to 59), 23% in the 30mg pegozafermin group (difference, 21%; 95% CI, 9 to 33), and 26% in the 44mg pegozafermin group (difference, 24%; 95% CI, 10 to 37). In summary, this study demonstrates that pegozafermin leads to improvements in fibrosis and NASH resolution in patients with biopsy-proven NASH.
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