上海2024年6月12日 /美通社/ -- 勃林格殷格翰近日宣布，胰高血糖素受體/胰高血糖素樣肽-1受體（GCGR/GLP-1R）雙重激動(dòng)劑survodutide(BI 456906)獲得中國(guó)國(guó)家藥品監(jiān)督管理局（NMPA）藥品審評(píng)中心（CDE）突破性療法認(rèn)定，擬用于代謝功能障礙相關(guān)脂肪性肝炎 (MASH) 的治療。
肝臟在心血管、腎臟和代謝系統(tǒng)中發(fā)揮著重要作用，主導(dǎo)著人體的新陳代謝。[3]MASH是一種進(jìn)行性疾病，影響全球超過(guò)1.15億人，[4]其歸因于肝臟炎癥并導(dǎo)致肝纖維化。[5]肝臟嚴(yán)重的組織疤痕（肝硬化）極大地增加終末期肝病和肝癌的風(fēng)險(xiǎn)，[6],[7]肝移植可能是目前唯一的治療選擇。[8]預(yù)計(jì)到2030年，MASH將成為肝移植的主要原因，[9]將給醫(yī)療系統(tǒng)帶來(lái)巨大的支付壓力。[10],[11]MASH還會(huì)影響一個(gè)人的生活質(zhì)量、人際關(guān)系和工作能力。[12]患者仍存在巨大的臨床未滿足需求。
Survodutide是一種具有獨(dú)特作用機(jī)制的胰高血糖素受體/胰高血糖素樣肽-1受體（GCGR/GLP-1R）雙重激動(dòng)劑。[13],[14] Survodutide中的胰高血糖素受體激動(dòng)劑組分能夠增加能量消耗，[15],[16]并且直接對(duì)肝臟產(chǎn)生影響，有助于改善肝纖維化。[13]而其GLP-1受體激動(dòng)劑組分則能有效降低食欲，同時(shí)增加飽腹感。[14],[17]
此次突破性療法認(rèn)定是基于其II期臨床試驗(yàn)，試驗(yàn)旨在評(píng)估每周皮下注射survodutide對(duì)伴有或未伴有2型糖尿病的MASH及（F1，F(xiàn)2，F(xiàn)3期）纖維化成人患者的治療效果。[18]試驗(yàn)達(dá)到其主要、關(guān)鍵次要終點(diǎn)和所有其他終點(diǎn)。研究結(jié)果顯示與安慰劑(18.2%)相比，高達(dá)83%接受survodutide (BI 456906) 治療的MASH成人患者實(shí)現(xiàn)了具有統(tǒng)計(jì)學(xué)意義的改善[組間差異：64.8%，(CI 51.1% - 78.6%), p<0.0001]，[13]在使用survodutide 48周后活檢組織學(xué)顯著改善且 F1、F2 和 F3 期纖維化（輕度至中度或晚期疤痕）無(wú)惡化。[1]關(guān)鍵次要終點(diǎn)結(jié)果顯示，高達(dá)52.3%的F1、F2和F3期成人MASH患者的纖維化顯著改善。亞組分析結(jié)果顯示，高達(dá)64.5%的F2和F3期纖維化（中度至晚期疤痕）成人患者的纖維化改善，且MASH無(wú)惡化。該臨床試驗(yàn)的完整數(shù)據(jù)結(jié)果已在2024年歐洲肝臟研究協(xié)會(huì)大會(huì)（EASL）上公布，并在《新英格蘭醫(yī)學(xué)雜志》上同步發(fā)表。[19],[20]
Survodutide是首個(gè)在為期48周治療的MASH II期臨床試驗(yàn)中取得如此顯著肝纖維化獲益的該類藥物。此前，survodutide于2021年被美國(guó)食品藥品管理局 (FDA) 授予快速審評(píng)資格，[21]并于去年11月，被歐洲藥品管理局 (EMA)授予優(yōu)先藥物(PRIME)資格。[22]
勃林格殷格翰大中華區(qū)研發(fā)和醫(yī)學(xué)負(fù)責(zé)人兼勃林格殷格翰中國(guó)炎癥免疫治療領(lǐng)域負(fù)責(zé)人張維博士表示："此次獲得CDE突破性療法認(rèn)定是survodutide開發(fā)過(guò)程中又一個(gè)重要里程碑，這也是中國(guó)國(guó)家藥品監(jiān)督管理局（NMPA）藥品審評(píng)中心（CDE）對(duì)這款治療代謝功能障礙相關(guān)脂肪性肝炎（MASH）創(chuàng)新藥物突破性臨床價(jià)值的認(rèn)可。上周發(fā)布的survodutide II期臨床試驗(yàn)的完整數(shù)據(jù)結(jié)果已經(jīng)驗(yàn)證了其作為同類最佳藥物的潛力，有望為MASH及臨床顯著纖維化的患者人群帶來(lái)變革性的治療。我們正在與相關(guān)部門保持緊密合作，推動(dòng)該創(chuàng)新藥的加速研發(fā)及早日獲批，并加速落地中國(guó)，讓中國(guó)廣大MASH及纖維化患者盡早從創(chuàng)新藥物治療中獲益。"
[1] Boehringer Ingelheim. Top-line Results From A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3). Data on file. |
[2] "Phase III studies to investigate survodutide for people living with obesity and overweight, with and without diabetes, cardiovascular disease and chronic kidney disease." Boehringer Ingelheim. www.boehringer-ingelheim.com/phase-3-studies-survodutide-obesity-and-overweight. Accessed May 2024 |
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[13] Top-line Results From A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)." Boehringer Ingelheim. Data on file |
[14] Zimmerman, Tina, et al. "BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy." Molecular Metabolism. Vol. 66, Dec. 2022, p. 101633. doi: 10.1016/j.molmet.2022.101633. |
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[18] "A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)." ClinicalTrials.gov. classic.clinicaltrials.gov/ct2/show/NCT04771273. Accessed May 2024 |
[19] Sanyal, Arun J. "Glucagon and GLP-1 receptor dual agonist survodutide improved liver histology in people with MASH and fibrosis: Results from a randomized, double-blind, placebo-controlled phase 2 trial". Oral presentation at European Association for the Study of the Liver Congress, Milan, Italy. 7June 2024. Abstract #LB117, presentation #GS-006. |
[20] Sanyal, Arun J., et al. "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis." The New England Journal of Medicine. June 2024. doi: 10.1056/NEJMoa2401755 |
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