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).

Pegozafermin 是一种人成纤维细胞生长因子 21 的长效糖聚乙二醇化类似物，正在开发用于治疗严重高甘油三酯血症 (SHTG) 和非酒精性脂肪性肝炎。在此，我们报告了一项 2 期、双盲、随机、五臂试验的结果，该试验在患有以下疾病的患者中测试了四种不同剂量的培戈扎芬明（ n = 67；52 名男性）与安慰剂（ n = 18；12 名男性）8 周的结果。 SHTG（甘油三酯（TG），≥500 mg dl ^-1且≤2,000 mg dl ^-1 ）。与安慰剂组相比，接受治疗的患者显示合并的培戈扎铁明组的中位 TG 显着降低（57.3% 与 11.9%，与安慰剂组的差异为 -43.7%，95% 置信区间 (CI)：-57.1%、-30.3%； P < 0.001） ，达到试验的主要终点。所有治疗组的中位 TG 降低范围为 36.4% 至 63.4%，并且无论背景降脂治疗如何，均保持一致。次要终点的结果包括平均载脂蛋白 B 和非高密度脂蛋白胆固醇浓度显着降低（合并剂量为 -10.5% 和 -18.3%，而安慰剂为 1.1% 和 -0.6%（95% CI：-21.5%， −2.0%； P = 0.019 和 95% CI：分别为 −30.7%、-5.1%； P = 0.007），并且与安慰剂组（ n = 6；-42.2% 合并培戈扎芬明，-8.3% 安慰剂；95% CI：-60.9%，-8.7%； P = 0.012），经磁共振成像子研究评估，未观察到相关的严重不良事件。如果这些结果在 3 期试验中得到证实，pegozafermin 可能是一种有前景的 SHTG 治疗方法（ClinicalTrials.gov 注册号：NCT0441186）。