Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study

被引：28

作者：

Harrison, Stephen A. ^{[1
,2
]}

Frias, Juan P. ^{[3
]}

Lucas, K. Jean ^{[4
]}

Reiss, Gary ^{[5
]}

Neff, Guy ^{[6
,7
]}

Bollepalli, Sureka ^{[8
]}

Su, Yan ^{[9
]}

Chan, Doreen ^{[10
]}

Tillman, Erik J. ^{[10
]}

Moulton, Ali ^{[10
]}

de Temple, Brittany ^{[10
]}

Zari, Arian ^{[10
]}

Shringarpure, Reshma ^{[10
]}

Rolph, Timothy ^{[10
]}

Cheng, Andrew ^{[10
]}

Yale, Kitty ^{[10
]}

机构：

[1] Univ Oxford, Oxford, England

[2] Pinnacle Clin Res, San Antonio, TX USA

[3] Veloc Clin Res, Los Angeles, CA USA

[4] Lucas Res, Morehead City, NC USA

[5] Tandem Clin Res, Marrero, LA USA

[6] Covenant Metab Specialists LLC, Sarasota, FL USA

[7] Covenant Res & Clin LLC, Ft Myers, FL USA

[8] Tampa Bay Med Res, Clearwater, FL USA

[9] Medpace, Cincinnati, OH USA

[10] Akero Therapeut Inc, 601 Gateway Blvd, South San Francisco, CA 94080 USA

来源：

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY | 2025年 / 23卷 / 01期

关键词：

Fibroblast Growth Factor 21; GLP-1; Analog; Hispanic/Latinx; NAFLD;

D O I：

10.1016/j.cgh.2024.02.022

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: In phase 2 studies, efruxifermin, an Fc-FGF21 analog, significantly reduced steatohepatitis and fi brosis in patients with non-alcoholic steatohepatitis, now called metabolic dysfunction- associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and effi cacy of efruxifermin in patients with MASH, fi brosis, and T2D taking a GLP-1RA. METHODS: Cohort D was a double-blind, placebo-controlled, phase 2b study in adults with T2D and MASH with fi brosis (F1-F3) on stable GLP-1RA therapy randomized (2:1) to receive efruxifermin 50 mg or placebo, once weekly for 12 weeks. The primary endpoint was safety and tolerability of efruxifermin added to a stable dose of GLP-1RA. Secondary endpoints included changes in hepatic fat fraction (HFF), markers of liver injury and fi brosis, and metabolic parameters. RESULTS: Adults (N = 31) with T2D and MASH fi brosis (F1-F3) on a stable GLP-1RA (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received efruxifermin 50 mg (n = 21) or placebo (n = 10) for 12 weeks. The addition of efruxifermin to a GLP-1RA appeared safe and well-tolerated. The most frequent efruxifermin-related adverse events were mild to moderate gastrointestinal events. One patient receiving efruxifermin discontinued due to nausea, and another withdrew consent. There were no treatment-related serious adverse events. After 12 weeks, efruxifermin reduced HFF by 65% (P < .0001 vs placebo) compared with a 10% reduction for placebo (GLP1RA alone). Efruxifermin also improved noninvasive markers of liver injury, fi brosis, glucose, and lipid metabolism while maintaining GLP-1RA-mediated weight loss. CONCLUSIONS: The tolerability profile of efruxifermin added to GLP-1RA appeared comparable to that of either drug alone, while also significantly reducing HFF and noninvasive markers of fi brosis in patients with MASH and T2D. Liver health in patients already on a GLP-1RA may be further improved by addition of efruxifermin.

引用

页码：103 / 113

页数：11

共 30 条

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