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關于代謝功能障礙相關脂肪性肝炎（<\/strong>MASH<\/strong>）<\/strong><\/p> \n

MASH是一種由肝臟中脂肪堆積引起的慢性進行性肝病，^{13,27<\/sup>也是代謝功能障礙相關脂肪性肝病（MASLD）中一種更為嚴重的類型。^{28<\/sup>根據美國的研究預測，從2015年至2030年，MASH的病例數將激增63%，從1650萬例攀升至2700萬例。^{16<\/sup> MASH與心血管、腎臟及多種代謝疾病之間存在著密切關聯。^{29,30<\/sup>據統計，高達34%的肥胖患者同時患有MASH。^{25<\/sup><\/p> \n}}}}}

MASH 嚴重程度使用F0至F4范圍內的等級進行評估，評估纖維化（疤痕）的水平：^{31<\/sup><\/p> \n}

\n
F0-F1：表示無纖維化或輕度纖維化<\/li> \n
F2-F3：表示中度或晚期纖維化<\/li> \n
F4：表示肝硬化<\/li> \n<\/ul> \n
關于本次臨床試驗（<\/strong>NCT04771273<\/strong>）<\/strong><\/p> \n
這是一項II期、隨機、雙盲、安慰劑對照的劑量探索性試驗，共納入了295名受試者。該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。^{10<\/sup><\/p> \n}
本次臨床試驗的主要終點是治療48周后，達到MASH組織學改善且纖維化無惡化的受試者百分比。^{10<\/sup> MASH的組織學改善定義為非酒精性脂肪肝病活動性評分（NAS）降低 ≥ 2分（總分為0 - 8分），包括NASH亞評分（小葉炎癥或氣球樣變）降低 ≥ 1分，同時確保纖維化分期不增加。^{10<\/sup> NAS評分代表了脂肪變性（肝脂肪積聚^{32<\/sup>）、小葉炎癥（炎癥細胞^{33<\/sup>）和氣球樣變（一種肝細胞變性^{34<\/sup>）的得分總和。<\/p> \n}}}}}
次要結局包括：^{10<\/sup><\/p> \n}
\n
治療48周后，肝臟脂肪含量相較于基線相對減少至少30%<\/li> \n
治療48周后，肝臟脂肪含量相較于基線的絕對和相對變化<\/li> \n
治療48周后，纖維化程度至少減少一個分期的（纖維化改善的定義）<\/li> \n
治療48周后，NAS總分相較于基線的絕對變化<\/li> \n<\/ul> \n
本次試驗采用劑量遞增的設計，包括2.4 mg、4.8 mg和6.0 mg三個治療組，劑量遞增階段持續24周，隨后進入為期24周的劑量維持階段。^{10<\/sup><\/p> \n}
關于<\/strong>Survodutide<\/strong>（<\/strong>BI456906<\/strong>）<\/strong><\/p> \n
Survodutide是一種胰高血糖素受體\/胰高血糖素樣肽-1受體（GCGR\/GLP-1R）雙重激動劑，可同時激活胰高血糖素受體和GLP-1受體，這對于控制代謝功能至關重要。^{6<\/sup><\/p> \n}
Zealand Pharma授權勃林格殷格翰全權負責survodutide的全球開發與商業化，保留了在北歐市場的聯合推廣權益。Survodutide是勃林格殷格翰在代謝心腎疾病領域研發組合的組成部分。<\/p> \n
2021年5月，survodutide用于MASH和纖維化治療成功獲得美國FDA的快速通道認定。^{21 <\/sup>23年11月，EMA將其納入PRIME計劃。^{22<\/sup><\/p> \n}}
勃林格針還對survodutide在肝硬化（F4）及不同程度肝功能障礙人群中進行了一項分兩部分的I期試驗。^{35<\/sup>第1部分試驗旨在探究肝硬化（F4）以及不同程度肝功能障礙對survodutide在人體內吸收方式的影響。第2部分試驗則旨在探究在肝硬化（F4）及不同程度肝功能障礙的超重和肥胖人群中，survodutide治療28周的耐受性。<\/p> \n}
Survodutide還正在五項針對超重和肥胖癥患者的III期研究中接受評估。^{2<\/sup>^{,23,24<\/sup>其中，SYNCHRONIZE-1和SYNCHRONIZE-2研究分別針對有合并癥但不伴和伴有2型糖尿病的亞組患者。^{2<\/sup> SYNCHRONIZE-CVOT研究則針對伴有心血管疾病、慢性腎病或心血管疾病風險因素的亞組人群。^{2<\/sup>在地域性研究中，日本的SYNCHRONIZE-JP和中國的SYNCHRONIZE-CN研究正致力于探索survodutide在肥胖癥患者亞人群中的治療效果。^{23,24 <\/sup>SYNCHRONIZE-JP研究探索survodutide與安慰劑相比，肝臟脂肪含量從基線到第76周的相對變化，此為關鍵次要終點。^{24<\/sup><\/p> \n}}}}}}
Reference：<\/span><\/strong><\/p> \n
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^{17 <\/sup>Khalil, Amjad, et al. “New Developments and Challenges in Liver Transplantation.” Journal of Clinical Medicine. <\/em>Vol 12, no. 17, Aug. 2023<\/span>, pp 5586.<\/em> doi: 10.3390\/jcm12175586.<\/p> \n}
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^{21 <\/sup> “Boehringer Ingelheim and Zealand Pharma Received FDA Fast Track Designation for Investigational Treatment for NASH.” Boehringer Ingelheim<\/em>.}www.boehringer-ingelheim.com\/us\/press-release\/boehringer-ingelheim-and-zealand-pharma-receive-fda-fast-track-designation<\/a>. Accessed June 2024<\/span><\/p> \n
^{22 <\/sup>“List of medicines currently in PRIME scheme.” European Medicines Agency<\/em>. December 2023<\/span>.}www.ema.europa.eu\/en\/documents\/other\/list-medicines-currently-prime-scheme_en.xlsx<\/a>. Accessed June 2024<\/span><\/p> \n
^{23 <\/sup>“A Study to Test Whether BI 456906 Helps Chinese People Living With Overweight or Obesity to Lose Weight.” Clinicaltrials.gov<\/em>.}clinicaltrials.gov\/study\/NCT06214741<\/a>. Accessed June 2024<\/span><\/p> \n
^{24<\/sup>“A Study to Test Whether BI 456906 Helps Japanese People Living With Obesity Disease (SYNCHRONIZE?JP).” Clinicaltrials.gov.<\/em>}clinicaltrials.gov\/study\/NCT06176365<\/a>. Accessed June 2024<\/span><\/p> \n
^{25<\/sup> Quek, Jingxuan, et al. ”Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis.” The Lancet Gastroenterology & Hepatology. <\/em>Vol. 8, no. 1, Jan. 2023<\/span>, pp. 20-30.}https:\/\/doi.org\/10.1016\/S2468-1253<\/a>(22)00317-X<\/p> \n
^{26<\/sup> “A Study to Test Whether Survodutide Helps People Living With Obesity or Overweight and With a Confirmed or Presumed Liver Disease Called Non-alcoholic Steatohepatitis (NASH) to Reduce Liver Fat and to Lose Weight”. Clinicaltrials.gov<\/em>.}https:\/\/clinicaltrials.gov\/study\/NCT06309992<\/a>. Accessed June 2024<\/span>.<\/p> \n
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^{30<\/sup> Schnell. Oliver, et al. <\/span>“CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.<\/span>” <\/span>Cardiovascular Diabetology<\/em><\/span>. Vol. 23, no. 1, Mar. 2024<\/span>. doi: 10.1186\/s12933-024-02180-8.<\/span><\/p> \n}
^{31<\/sup> Kleiner, David E., et al. “Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.” Hepatology<\/em>. Vol. 41, no. 6, June 2005<\/span>, pp. 1313-21. doi: 10.1002\/hep.20701.<\/p> \n}
^{32 <\/sup> “Non-alcoholic fatty liver disease (NAFLD).” NHS<\/em>.}www.nhs.uk\/conditions\/non-alcoholic-fatty-liver-disease<\/a>. Accessed June 2024<\/span><\/p> \n
^{33<\/sup> Vanderbeck, Scott, et al. “Automatic quantification of lobular inflammation and hepatocyte ballooning in nonalcoholic fatty liver disease liver biopsies.” Human Pathology.<\/em> Vol. 46, no. 5, May 2015<\/span>, pp. 767-75. doi: 10.1016\/j.humpath.2015.01.019.<\/p> \n}
^{34<\/sup> Caldwell, Stephan, et al. “Hepatocellular ballooning in NASH.” Journal of Hepatology<\/em>. Vol. 53, no. 4, Oct. 2010<\/span>, pp 719-23. doi: 10.1016\/j.jhep.2010.04.031.<\/p> \n}
^{35 <\/sup>“A Study to (1) Compare How BI 456906 is Taken up in the Body of Healthy People and People With Liver Problems and (2) Find Out How People With Overweight and Obesity, With and Without Liver Problems, Tolerate Different Doses of BI 456906.” Clinicaltrials.gov<\/em>.}clinicaltrials.gov\/study\/NCT05296733<\/a>. Accessed June 2024<\/span><\/p> \n
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