美国Akero Therapeutics公司Kitty Yale研究团队报道了Efruxifermin 治疗非酒精性脂肪肝炎(NASH)的 2a 期试验结果。相关论文于2021年7月8日发表于国际学术期刊《自然-医学》杂志。

研究人员评估了efruxifermin（一种长效Fc-成纤维细胞生长因子21 (FGF21)融合蛋白）治疗NASH的安全性和有效性。BALANCED是一项在美国27个中心NASH患者中进行的随机、安慰剂对照研究。80名患者，根据肝脂肪分数 (HFF) 和纤维化阶段分类，按照1:1:1:1 的比例随机分配接受安慰剂 (n = 21)或efruxifermin 28 mg (n = 19)、efruxifermin 50 mg (n = 20)或efruxifermin 70 mg (n = 20)治疗，每周皮下注射，共持续16周。第12周时通过磁共振成像测量的HFF相对于基线的绝对变化以及质子密度脂肪分数是该临床试验的主要终点。

对于完整的分析集，HFF的基线最小二乘平均绝对变化（单侧 97.5%置信区间）在28-、50-和70-mg组中分别为-12.3% (-infinity (-inf), -10.3), -13.4% (-inf, -11.4 )和-14.1% (-inf, -12.1) ，而安慰剂组的数据为 0.3% (-inf, 1.6)，在统计学上efruxifermin组与安慰剂之间存在显著差异（每个P < 0.0001）。

总体而言，接受研究药物的79名患者中有70名 (89%) 至少出现一次治疗引起的不良事件 (TEAE)，其中大多数为1-2级 (64 (81%))、5名(6%)为3级和一名为4级。最常报告的与药物相关的TEAE是1-2级胃肠道反应（36 (46%)）。efruxifermin 治疗显著降低了F1-F3期NASH患者的HFF，具有可接受的安全性。 

据悉，临床前和临床数据表明，FGF21具有抗纤维化作用，可改善代谢状态并具有治疗非酒精性脂肪性肝炎的潜力。

附：英文原文

Title: Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial

Author: Stephen A. Harrison, Peter J. Ruane, Bradley L. Freilich, Guy Neff, Rashmee Patil, Cynthia A. Behling, Chen Hu, Erica Fong, Brittany de Temple, Erik J. Tillman, Timothy P. Rolph, Andrew Cheng, Kitty Yale

Issue&Volume: 2021-07-08

Abstract: Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1:1:1:1 to receive placebo (n=21) or efruxifermin 28mg (n=19), efruxifermin 50mg (n=20) or efruxifermin 70mg (n=20) via weekly subcutaneous injection for 16 weeks. The primary endpoint—absolute change from baseline in HFF measured as magnetic resonance imaging–proton density fat fraction at week 12—was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were 12.3% (infinity (inf), 10.3), 13.4% (inf, 11.4) and 14.1% (inf, 12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P<0.0001 each). Overall, 70 of 79 patients who received the study drug (89%) experienced at least one treatment-emergent adverse event (TEAE), with the majority grade 1–2 (64 (81%)), five (6%) grade 3 and one grade 4. The most commonly reported drug-related TEAEs were grade 1–2 gastrointestinal (36 (46%)). Treatment with efruxifermin significantly reduced HFF in patients with F1–F3 stage NASH, with an acceptable safety profile.

DOI: 10.1038/s41591-021-01425-3

Source: https://www.nature.com/articles/s41591-021-01425-3