Journal Article

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial

Andrawis, Nabil S., Feng, Shibao, Wasilewska, Katarzyna, Sterling, Lulu, Mansbach, Hank, Cain, James E., Hartsfield, Cynthia L., Agollah, Germaine D., Parli, Teresa, Tseng, Leo, Bays, Harold E., Miller, Michael, Bhatt, Deepak L., Kastelein, John J. P.

2023

Overview

Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment of severe hypertriglyceridemia (SHTG) and nonalcoholic steatohepatitis. Here we report the results of a phase 2, double-blind, randomized, five-arm trial testing pegozafermin at four different doses ( n  = 67; 52 male) versus placebo ( n  = 18; 12 male) for 8 weeks in patients with SHTG (triglycerides (TGs), ≥500 mg dl −1 and ≤2,000 mg dl −1 ). Treated patients showed a significant reduction in median TGs for the pooled pegozafermin group versus placebo (57.3% versus 11.9%, difference versus placebo −43.7%, 95% confidence interval (CI): −57.1%, −30.3%; P  < 0.001), meeting the primary endpoint of the trial. Reductions in median TGs ranged from 36.4% to 63.4% across all treatment arms and were consistent regardless of background lipid-lowering therapy. Results for secondary endpoints included significant decreases in mean apolipoprotein B and non-high-density lipoprotein cholesterol concentrations (−10.5% and −18.3% for pooled doses compared to 1.1% and −0.6% for placebo (95% CI: −21.5%, −2.0%; P  = 0.019 and 95% CI: −30.7%, −5.1%; P  = 0.007, respectively), as well as a significant decrease in liver fat fraction for pooled treatment ( n  = 17) versus placebo ( n  = 6; −42.2% pooled pegozafermin, −8.3% placebo; 95% CI: −60.9%, −8.7%; P  = 0.012), as assessed in a magnetic resonance imaging sub-study. No serious adverse events were observed to be related to the study drug. If these results are confirmed in a phase 3 trial, pegozafermin could be a promising treatment for SHTG (ClinicalTrials.gov registration: NCT0441186). In a phase 2, randomized clinical trial in patients with severe hypertriglyceridemia, pegozafermin, a long-acting analog of human fibroblast growth factor 21, was safe and met the primary endpoint of the trial for reducing serum triglyceride levels.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308 / 692/308/2779 / Apolipoprotein B / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cholesterol / Clinical trials / Double-Blind Method / Fatty liver / Fibroblast Growth Factors - therapeutic use / Fibroblasts / Growth factors / High density lipoprotein / Humans / Hypertriglyceridemia / Hypertriglyceridemia - complications / Hypertriglyceridemia - drug therapy / Infectious Diseases / Lipids / Magnetic resonance imaging / Male / Males / Metabolic Diseases / Molecular Medicine / Neurosciences / Non-alcoholic Fatty Liver Disease - complications / Non-alcoholic Fatty Liver Disease - drug therapy / Patients / Placebos / Treatment Outcome / Triglycerides