SYNCHRONIZE-CVOT试验达到主要终点，索弗度肽（survodutide）成为全球首个证实心血管安全性的胰高血糖素/GLP-1双受体激动剂

关于肥胖和超重

目前，全球已有超过10亿人患有肥胖，相当于每8人中就有1人。到2030年，全球肥胖人数可能将达到2010年的两倍以上。²⁰超重和肥胖是复杂的慢性疾病，其特征为异常或过度的脂肪蓄积，并可能对整体健康构成风险。²¹

关于索弗度肽（BI 456906）

索弗度肽（survodutide）是一种胰高血糖素/GLP-1双重受体激动剂，可同时激活胰高血糖素受体和GLP-1受体，这两种受体均参与代谢功能的调节。^12,22,23

索弗度肽（survodutide）目前仍处于研究阶段，尚未获批使用，其疗效和安全性尚未确立。目前，索弗度肽正在一项全面的III期临床开发项目中接受评估，其中包括针对超重或肥胖人群开展的SYNCHRONIZE系列研究，以及针对MASH伴肝纤维化患者开展的LIVERAGE系列研究。^{17,18,19,24,25,26,27,28,29}

索弗度肽（survodutide）在治疗非肝硬化MASH伴中度或进展期肝纤维化（2期或3期）的成人患者方面具有潜力，并已获得美国食品药品监督管理局（FDA）的认可，包括：

· 2021年5月获授快速通道资格（Fast Track designation）；³⁰

· 2024年9月获授突破性疗法认定（Breakthrough Therapy designation）。³¹

索弗度肽（survodutide）在治疗MASH伴肝纤维化成人患者方面的潜力也获得了其他监管机构的认可，包括：

· 欧洲药品管理局（EMA）于2023年11月将其纳入优先药物（PRIME）计划；³²

· 中国国家药品监督管理局（NMPA）药品审评中心（CDE）于2024年6月授予其突破性治疗品种认定；

· 中国台湾地区食品药物管理部门于2024年9月授予其突破性疗法认定。

索弗度肽（survodutide）由Zealand Pharma授权给勃林格殷格翰，勃林格殷格翰独家负责其全球开发和商业化。索弗度肽（survodutide）是勃林格殷格翰心血管、肾脏和代谢疾病领域研发管线的重要组成部分。  

关于SYNCHRONIZE-CVOT 试验（NCT06077864）

SYNCHRONIZE-CVOT是一项III期、双盲、安慰剂对照、事件驱动的心血管安全性研究，共纳入5,530名超重或肥胖成人受试者，这些受试者已确诊心血管疾病（CVD）或慢性肾脏病，和/或至少伴有两项体重相关并发症或心血管疾病风险因素。²⁷受试者每周接受一次索弗度肽（survodutide）注射，剂量为3.6mg或6.0mg，或接受安慰剂。试验的主要终点为首次发生经独立判定的复合终点中任一事件的时间，包括心血管死亡、非致死性卒中、非致死性心肌梗死、缺血相关冠状动脉血运重建或心力衰竭事件（HFE），以评估非劣效性。²⁷

该研究共设有27项次要终点和关键次要终点，包括：²⁷

· 首次发生经独立判定的3P-MACE任一组成事件的时间（包括心血管死亡、非致死性卒中或非致死性心肌梗死）

· 收缩压（SBP）的绝对变化

· 腰围的绝对变化

· 体重的百分比变化

关于SYNCHRONIZE系列研究

索弗度肽（survodutide）已在另外三项针对超重或肥胖人群的全球III期临床研究中接受评估：

· 纳入未患2型糖尿病的成人受试者；²⁴

· 纳入存在代谢相关脂肪性肝病（MASLD）风险，且已确诊或疑似患有MASH的成人受试者；²⁶

· 纳入患有2型糖尿病的成人受试者。²⁵

索弗度肽（survodutide）还正在两项III期区域性临床试验中接受评估：

· 目前在日本和中国开展的研究正在评估索弗度肽（survodutide）用于肥胖特定亚组人群的疗效和安全性。其中，SYNCHRONIZE-JP将索弗度肽（survodutide）与安慰剂相比，从基线至第76周肝脏脂肪含量及身体成分参数的相对变化作为次要终点进行评估。^28,29

作为更广泛临床证据开发项目的一部分，多项IIIb期研究正在推进，旨在进一步探索肥胖人群及真实世界诊疗中尚未满足的重要需求，包括：

· SYNCHRONIZE-HERA将评估索弗度肽（survodutide）在女性健康领域的应用。¹⁵

· ELEVATE-LIVER将评估索弗度肽（survodutide）对代谢相关脂肪性肝病（MASLD）或早期代谢相关脂肪性肝炎（MASH）患者心脏功能和结构维持的影响。¹⁶

· SYNCHRONIZE-START将探索真实世界中的剂量递增策略，包括治疗起始以及从GLP-1受体激动剂（GLP-1 RAs）转换治疗，并重点关注治疗耐受性。¹⁴

此外，该研究还将评估索弗度肽（survodutide）对改善2型糖尿病（T2D）成人患者血糖控制的作用。这些患者目前仅通过饮食和运动进行管理，或在此基础上联合使用包括胰岛素在内的糖尿病治疗药物。¹⁷

关于LIVERAGE 和 LIVERAGE-Cirrhosis 

LIVERAGE和LIVERAGE-Cirrhosis是两项全球III期临床试验，分别评估索弗度肽（survodutide）在伴有2期或3期肝纤维化的MASH成人患者，以及伴有代偿期MASH肝硬化（4期肝纤维化）的成人患者中的疗效和安全性。^18,19

LIVERAGE计划入组约1,800名成人受试者，LIVERAGE-Cirrhosis计划入组约1,590名成人受试者。在两项试验中，受试者均被随机分组，每周接受一次索弗度肽（survodutide）或安慰剂注射，其中索弗度肽（survodutide）逐步递增至最高剂量。^18,19

参考文献

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