TY - JOUR
T1 - The FGF21 analog pegozafermin in severe hypertriglyceridemia
T2 - a randomized phase 2 trial
AU - Bhatt, Deepak L.
AU - Bays, Harold E.
AU - Miller, Michael
AU - Cain, James E.
AU - Wasilewska, Katarzyna
AU - Andrawis, Nabil S.
AU - Parli, Teresa
AU - Feng, Shibao
AU - Sterling, Lulu
AU - Tseng, Leo
AU - Hartsfield, Cynthia L.
AU - Agollah, Germaine D.
AU - Mansbach, Hank
AU - ENTRIGUE Principal Investigators
AU - Kastelein, John J. P.
N1 - Funding Information: The authors would like to thank the volunteers who participated in the phase 2 trial described herein. The studies in this report were supported by 89bio, Inc. We thank Antaros Medical for providing MRI-PDFF images, J. Eastman, Dennig Marketing Group, for data table and figure creation, and D. Norris Ph.D., Ecosse Medical Communications, LLC, for writing assistance (the first draft of the manuscript was written by D.L.B.). Publisher Copyright: © 2023, The Author(s).
PY - 2023/7
Y1 - 2023/7
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85162979661&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41591-023-02427-z
DO - https://doi.org/10.1038/s41591-023-02427-z
M3 - Article
C2 - 37355760
SN - 1078-8956
VL - 29
SP - 1782
EP - 1792
JO - Nature medicine
JF - Nature medicine
IS - 7
ER -