Danese Silvio, Rothenberg Michael E, Lim Jeremy J, Ding Han Ting, McBride Jacqueline M, Chen Yiling, Dash Ajit, Mar Jordan S, Keir Mary, Peyrin-Biroulet Laurent, Panes Julian, Colombel Jean-Frederic, Feagan Brian, Valentine John F, Schreiber Stefan
Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano Italy.
Genentech, Inc, South San Francisco, California.
Clin Gastroenterol Hepatol. 2025 Jul;23(8):1387-1397. doi: 10.1016/j.cgh.2024.11.013. Epub 2024 Dec 16.
BACKGROUND & AIMS: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared with vedolizumab in patients with ulcerative colitis (UC).
This randomized phase II trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n = 43], 60 μg/kg [n = 44], and 90 μg/kg [n = 43]) compared with placebo (n = 22) and with vedolizumab (n = 43) in the treatment of moderate to severe UC. Key clinical outcomes were assessed through the modified Mayo Clinic Score, and endoscopic evaluations by a central reader.
Efmarodocokin alfa was adequately tolerated with an acceptable safety profile. Although efmarodocokin alfa did not show statistically significant improvement in clinical remission, clinical response, endoscopic healing, or endoscopic remission at week 8 compared with placebo, vedolizumab demonstrated some efficacy. Clinical remission was achieved by 12%, 9%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 9% and 26% of patients in the placebo and vedolizumab arms at week 8. Similarly, endoscopic healing at week 8 was achieved by 14%, 14%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 14% and 33% of patients in the placebo and vedolizumab arms. A dose-dependent increase in pharmacodynamic biomarkers was observed (regenerating islet-derived protein 3-alpha and C-reactive protein levels).
Efmarodocokin alfa did not demonstrate efficacy compared with placebo, and this phase II study was ended early for futility; however, there was evidence of target engagement (skin adverse events, regenerating islet-derived protein 3-alpha levels).
gov, Number: NCT03558152.
阿法依泊汀是一种白细胞介素（IL）-22激动剂，具有良好的药代动力学特性和可接受的安全性。本研究进一步探讨了与维多珠单抗相比，阿法依泊汀在溃疡性结肠炎（UC）患者中的治疗潜力。
这项随机II期试验评估了每4周静脉注射3种剂量阿法依泊汀（30μg/kg [n = 43]、60μg/kg [n = 44]和90μg/kg [n = 43]）与安慰剂（n = 22）和维多珠单抗（n = 43）治疗中度至重度UC的疗效、安全性、药代动力学和药效学。通过改良的梅奥诊所评分评估关键临床结局，并由中心阅片者进行内镜评估。
阿法依泊汀耐受性良好，安全性可接受。尽管与安慰剂相比，阿法依泊汀在第8周时临床缓解、临床反应、内镜愈合或内镜缓解方面未显示出统计学上的显著改善，但维多珠单抗显示出一定疗效。在第8周时，30μg/kg、60μg/kg和90μg/kg剂量组分别有12%、9%和12%的患者实现临床缓解，而安慰剂组和维多珠单抗组分别为9%和26%。同样，在第8周时，30μg/kg、60μg/kg和90μg/kg剂量组分别有14%、14%和12%的患者实现内镜愈合，而安慰剂组和维多珠单抗组分别为14%和33%。观察到药效学生物标志物呈剂量依赖性增加（再生胰岛衍生蛋白3-α和C反应蛋白水平）。
与安慰剂相比，阿法依泊汀未显示出疗效，该II期研究因无效而提前结束；然而，有证据表明其作用于靶点（皮肤不良事件、再生胰岛衍生蛋白3-α水平）。
美国国立医学图书馆临床试验注册中心，编号：NCT03558152
