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）雙重激動劑survodutide(BI 456906)獲得中國國家藥品監督管理局（NMPA）藥品審評中心（CDE）突破性療法認定，擬用于代謝功能障礙相關脂肪性肝炎 (MASH) 的治療。
肝臟在心血管、腎臟和代謝系統中發揮著重要作用，主導著人體的新陳代謝。[3]MASH是一種進行性疾病，影響全球超過1.15億人，[4]其歸因于肝臟炎癥并導致肝纖維化。[5]肝臟嚴重的組織疤痕（肝硬化）極大地增加終末期肝病和肝癌的風險，[6],[7]肝移植可能是目前唯一的治療選擇。[8]預計到2030年，MASH將成為肝移植的主要原因，[9]將給醫療系統帶來巨大的支付壓力。[10],[11]MASH還會影響一個人的生活質量、人際關系和工作能力。[12]患者仍存在巨大的臨床未滿足需求。
Survodutide是一種具有獨特作用機制的胰高血糖素受體/胰高血糖素樣肽-1受體（GCGR/GLP-1R）雙重激動劑。[13],[14] Survodutide中的胰高血糖素受體激動劑組分能夠增加能量消耗，[15],[16]并且直接對肝臟產生影響，有助于改善肝纖維化。[13]而其GLP-1受體激動劑組分則能有效降低食欲，同時增加飽腹感。[14],[17]
此次突破性療法認定是基于其II期臨床試驗，試驗旨在評估每周皮下注射survodutide對伴有或未伴有2型糖尿病的MASH及（F1，F2，F3期）纖維化成人患者的治療效果。[18]試驗達到其主要、關鍵次要終點和所有其他終點。研究結果顯示與安慰劑(18.2%)相比，高達83%接受survodutide (BI 456906) 治療的MASH成人患者實現了具有統計學意義的改善[組間差異：64.8%，(CI 51.1% - 78.6%), p<0.0001]，[13]在使用survodutide 48周后活檢組織學顯著改善且 F1、F2 和 F3 期纖維化（輕度至中度或晚期疤痕）無惡化。[1]關鍵次要終點結果顯示，高達52.3%的F1、F2和F3期成人MASH患者的纖維化顯著改善。亞組分析結果顯示，高達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無惡化。該臨床試驗的完整數據結果已在2024年歐洲肝臟研究協會大會（EASL）上公布，并在《新英格蘭醫學雜志》上同步發表。[19],[20]
Survodutide是首個在為期48周治療的MASH II期臨床試驗中取得如此顯著肝纖維化獲益的該類藥物。此前，survodutide于2021年被美國食品藥品管理局 (FDA) 授予快速審評資格，[21]并于去年11月，被歐洲藥品管理局 (EMA)授予優先藥物(PRIME)資格。[22]
勃林格殷格翰大中華區研發和醫學負責人兼勃林格殷格翰中國炎癥免疫治療領域負責人張維博士表示："此次獲得CDE突破性療法認定是survodutide開發過程中又一個重要里程碑，這也是中國國家藥品監督管理局（NMPA）藥品審評中心（CDE）對這款治療代謝功能障礙相關脂肪性肝炎（MASH）創新藥物突破性臨床價值的認可。上周發布的survodutide II期臨床試驗的完整數據結果已經驗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變革性的治療。我們正在與相關部門保持緊密合作，推動該創新藥的加速研發及早日獲批，并加速落地中國，讓中國廣大MASH及纖維化患者盡早從創新藥物治療中獲益。"
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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. |
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