Survodutide有望成为治疗代谢功能障碍相关脂肪性肝炎 (MASH)*的同类最佳药物，在II期试验中与安慰剂相比，经过 48 周的治疗后达到了主要和关键的次要终点
Survodutide是一种新型胰高血糖素受体/胰高血糖素样肽-1受体（GCGR/GLP-1R）双重激动剂，已证明其对肥胖人群有效1，并且在MASH人群中具有统计学意义的结果表明2，有望为心血管、肾脏和代谢疾病带来具有临床意义的积极作用
二期试验的完整数据将在未来几个月内公布
勃林格殷格翰今日宣布，在一项II期试验中，与安慰剂(18.2%)相比，高达83%接受survodutide (BI 456906) 治疗的MASH成人患者取得了具有统计学意义的改善[反应差异：64.8%，(CI 51.1% - 78.6%), p<0.0001]2。该试验达到了主要终点，在使用survodutide48周后MASH活检结果改善且 F1、F2 和 F3 期纤维化（轻度至中度或晚期疤痕）无恶化2。Survodutide还达到了所有次要终点，包括肝纤维化的统计学显著改善。完整数据将在未来几个月内公布。
Survodutide有望成为MASH的同类最佳治疗药物，MASH是一种与心血管、肾脏和代谢疾病相关的肝脏疾病3,4,5,6。
Survodutide是一种GCGR/GLP-1R双重激动剂，具有新型作用机制，也是首个在MASH II期试验中显示出这种获益水平的此类药物2,7。Survodutide中的胰高血糖素激动剂成分具有增加能量消耗的潜力7，且可直接作用于肝脏，有望改善肝纤维化2。GLP-1 激动剂成分可降低食欲，同时增加饱腹感7,8。
弗吉尼亚州联邦大学医学院医学、生理学和分子病理学教授、该实验的主要研究者Arun Sanyal博士表示：“我很高兴地看到survodutide在MASH和肝纤维化方面的II期试验取得的这些具有统计学意义的结果。这些数据使survodutide有望成为一种潜在的领先疗法，为存在巨大未被满足医疗需求的MASH和肝纤维化患者带来希望。我期待在今年上半年的学术大会上分享关于关键次要终点的更多细节，包括有纤维化改善的患者的比例。”
勃林格殷格翰全球人用药品负责人Carinne Brouillon表示：“MASH研究结果表明survodutide有望成为同类最佳的治疗药物，我们相信其真正的差异化因素是直接作用于肝脏的胰高血糖素受体激动作用。为了将这种潜在的疗法带给超过10亿的受心血管-肾脏-代谢疾病相关联影响的患者，我们将尽快推进MASH领域的研究进程。我们也在同步推进survodutide在其他相关疾病方面的进展，目前已经启动其在肥胖的III期临床试验项目。”
肝脏主导着人体的新陈代谢，因此在心血管、肾脏和代谢系统中发挥着重要作用9。 MASH 是一种进行性疾病，影响全球超过 1.15 亿人10，其归因于肝脏炎症并导致肝纤维化11。肝脏严重的组织疤痕（肝硬化）极大地增加终末期肝病和肝癌的风险5，肝移植可能是唯一的治疗选择12。 预计到 2030 年，MASH将成为肝移植的主要原因13，将给医疗系统带来巨大的支付压力14,15。MASH还会影响一个人的生活质量、人际关系和工作能力16。尽管存在这些负担，然而目前缺乏靶向治疗，尚无获批上市的药物。
这项双盲、安慰剂对照的II期试验探索了survodutide的三种剂量（2.4 mg、4.8 mg 和 6.0 mg）17。最重要的结果表明，该试验覆盖的所有剂量均对MASH有所改善2。Survodutide治疗并未出现意外的安全性或耐受性问题，包括在6.0mg的较高剂量下2。
此前，survodutide于2021年被美国食品药品管理局 (FDA) 授予快速审评资格18，并于去年11月，被欧洲药品管理局 (EMA)授予进入治疗纤维化MASH的优先审评药物(PRIME) 资格19。这些审评流程旨在帮助加快治疗严重疾病药物的审批，满足治疗领域未被满足的需求，尽早为患者带来重磅的新药物。
Survodutide还有五项在研的针对超重或肥胖关键亚型人群的III期研究20。SYNCHRONIZE-1和SYNCHRONIZE-2亚型分别包括患有合并症不伴有或伴有2型糖尿病的患者20。SYNCHRONIZE-CVOT试验亚型人群包括患有心血管疾病、慢性肾脏疾病或具有心血管疾病风险因素的人20。除此之外，勃林格殷格翰正在日本(SYNCHRONIZE-JP)和中国(SYNCHRONIZE-CN)开展survodutide在特定肥胖人群的 III 期临床试验21,22。
关于代谢功能障碍相关脂肪性肝炎 (MASH)
MASH是一种由肝脏中脂肪堆积引起的慢性进行性肝病11,24,25，也是一种更严重的代谢功能障碍相关脂肪性肝病 (MASLD)26。大约20-30%的MASLD患者会继续发展为 MASH27，预计2015年至2030年，MASH病例数将增加 63%，从1650万例增至2700万例12。MASH是一种与心血管、肾脏和代谢疾病密切相关的疾病6,28。据估计，34%的肥胖患者同时患有MASH29。MASH也是西方国家肝移植增长最快的原因14。
MASH严重程度使用 F0 至 F4 范围内的等级进行评估，评估纤维化（疤痕）的水平30：
• F0-F1：表示无纤维化或轻度纤维化
• F2-F3：表示中度或晚期/重度纤维化
• F4：表示肝硬化
关于Survodutide
Survodutide 是一种GCGR/GLP-1R双重激动剂，可同时激活胰高血糖素样肽-1（ GLP-1 ）受体和胰高血糖素（GCG）受体，这对于控制代谢功能至关重要7。在另一项II期研究中评估了survodutide对NASH和肝纤维化（F1/F2/F3期）成人患者（无论是否患有2型糖尿病）的治疗效果，该研究获得了美国FDA的快速通道认定。Survodutide由勃林格殷格翰和Zealand Pharma联合开发，是勃林格殷格翰在代谢心肾疾病领域研发组合的组成部分。
关于勃林格殷格翰
勃林格殷格翰致力于研究突破性疗法，旨在变革生命，守护世世代代的健康。作为一家研发驱动的全球领先生物制药企业，公司在医疗需求高度未得到满足的领域通过创新展现价值。勃林格殷格翰自1885年成立以来一直是一家独立的家族企业，始终着眼长远与可持续发展。在人用药品、动物保健两大业务领域，全球有超过5.3万名员工服务逾130个地区。更多详情，请访问：www.boehringer-ingelheim.com
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