(function(){
			var content_array=["<p><strong>关于代谢功能障碍相关脂肪性肝炎（<\/strong><strong>MASH<\/strong><strong>）<\/strong><\/p> \n<p>MASH是一种由肝脏中脂肪堆积引起的慢性进行性肝病，<sup>13,27<\/sup>也是代谢功能障碍相关脂肪性肝病（MASLD）中一种更为严重的类型。<sup>28<\/sup>根据美国的研究预测，从2015年至2030年，MASH的病例数将激增63%，从1650万例攀升至2700万例。<sup>16<\/sup> MASH与心血管、肾脏及多种代谢疾病之间存在着密切关联。<sup>29,30<\/sup>据统计，高达34%的肥胖患者同时患有MASH。<sup>25<\/sup><\/p> \n<p>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：<sup>31<\/sup><\/p> \n<ul type=\"disc\"> \n <li>F0-F1：表示无纤维化或轻度纤维化<\/li> \n <li>F2-F3：表示中度或晚期纤维化<\/li> \n <li>F4：表示肝硬化<\/li> \n<\/ul> \n<p><strong>关于本次临床试验（<\/strong><strong>NCT04771273<\/strong><strong>）<\/strong><\/p> \n<p>这是一项II期、随机、双盲、安慰剂对照的剂量探索性试验，共纳入了295名受试者。该试验旨在评估每周皮下注射survodutide对伴有或未伴有2型糖尿病的MASH及（F1，F2，F3期）纤维化成人患者的治疗效果。<sup>10<\/sup><\/p> \n<p>本次临床试验的主要终点是治疗48周后，达到MASH组织学改善且纤维化无恶化的受试者百分比。<sup>10<\/sup> MASH的组织学改善定义为非酒精性脂肪肝病活动性评分（NAS）降低 ≥ 2分（总分为0 - 8分），包括NASH亚评分（小叶炎症或气球样变）降低 ≥ 1分，同时确保纤维化分期不增加。<sup>10<\/sup> NAS评分代表了脂肪变性（肝脂肪积聚<sup>32<\/sup>）、小叶炎症（炎症细胞<sup>33<\/sup>）和气球样变（一种肝细胞变性<sup>34<\/sup>）的得分总和。<\/p> \n<p>次要结局包括：<sup>10<\/sup><\/p> \n<ul type=\"disc\"> \n <li>治疗48周后，肝脏脂肪含量相较于基线相对减少至少30%<\/li> \n <li>治疗48周后，肝脏脂肪含量相较于基线的绝对和相对变化<\/li> \n <li>治疗48周后，纤维化程度至少减少一个分期的（纤维化改善的定义）<\/li> \n <li>治疗48周后，NAS总分相较于基线的绝对变化<\/li> \n<\/ul> \n<p>本次试验采用剂量递增的设计，包括2.4 mg、4.8 mg和6.0 mg三个治疗组，剂量递增阶段持续24周，随后进入为期24周的剂量维持阶段。<sup>10<\/sup><\/p> \n<p><strong>关于<\/strong><strong>Survodutide<\/strong><strong>（<\/strong><strong>BI456906<\/strong><strong>）<\/strong><\/p> \n<p>Survodutide是一种胰高血糖素受体\/胰高血糖素样肽-1受体（GCGR\/GLP-1R）双重激动剂，可同时激活胰高血糖素受体和GLP-1受体，这对于控制代谢功能至关重要。<sup>6<\/sup><\/p> \n<p>Zealand Pharma授权勃林格殷格翰全权负责survodutide的全球开发与商业化，保留了在北欧市场的联合推广权益。Survodutide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。<\/p> \n<p>2021年5月，survodutide用于MASH和纤维化治疗成功获得美国FDA的快速通道认定。<sup>21 <\/sup>23年11月，EMA将其纳入PRIME计划。<sup>22<\/sup><\/p> \n<p>勃林格针还对survodutide在肝硬化（F4）及不同程度肝功能障碍人群中进行了一项分两部分的I期试验。<sup>35<\/sup>第1部分试验旨在探究肝硬化（F4）以及不同程度肝功能障碍对survodutide在人体内吸收方式的影响。第2部分试验则旨在探究在肝硬化（F4）及不同程度肝功能障碍的超重和肥胖人群中，survodutide治疗28周的耐受性。<\/p> \n<p>Survodutide还正在五项针对超重和肥胖症患者的III期研究中接受评估。<sup>2<\/sup><sup>,23,24<\/sup>其中，SYNCHRONIZE-1和SYNCHRONIZE-2研究分别针对有合并症但不伴和伴有2型糖尿病的亚组患者。<sup>2<\/sup>&nbsp;SYNCHRONIZE-CVOT研究则针对伴有心血管疾病、慢性肾病或心血管疾病风险因素的亚组人群。<sup>2<\/sup>在地域性研究中，日本的SYNCHRONIZE-JP和中国的SYNCHRONIZE-CN研究正致力于探索survodutide在肥胖症患者亚人群中的治疗效果。<sup>23,24 <\/sup>SYNCHRONIZE-JP研究探索survodutide与安慰剂相比，肝脏脂肪含量从基线到第76周的相对变化，此为关键次要终点。<sup>24<\/sup><\/p> \n<p><strong><span>Reference：<\/span><\/strong><\/p> \n<p><span>1<\/span> <span>Sanyal, Arun J. &quot;<\/span>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”. <span>Oral presentation at European Association for the Study of the Liver Congress, <span class=\"xn-location\">Milan, Italy<\/span>. 7June 2024. Abstract #LB117, presentation #GS-006.<\/span><\/p> \n<p><span>2<\/span><span> “Phase III studies to investigate survodutide for people living with obesity and overweight, with and without diabetes, cardiovascular disease and<\/span> <span>chronic kidney disease.” <\/span><em><span>Boehringer Ingelheim<\/span><\/em><span>. <\/span><a href=\"https:\/\/t.prnasia.com\/t\/yTHgbriJ\" rel=\"nofollow\" target=\"_blank\"><span>www.boehringer-ingelheim.com\/phase-3-studies-survodutide-obesity-and-overweight<\/span><\/a><span>. <\/span><span>Accessed <span class=\"xn-chron\">June 2024<\/span><\/span><\/p> \n<p><span>3<\/span> <span>Sanyal, Arun J., et al. “Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.” The New England Journal of Medicine. Vol. 385, no. 17, 2021, pp. 1559-1569. doi: 10.1056\/NEJMoa2029349<\/span><\/p> \n<p><span>4<\/span> <span>Sanyal, Arun J., et al. “A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.” <em>The New England Journal of Medicine. <\/em>June 2024.&nbsp;doi: 10.1056\/NEJMoa2401755<\/span><\/p> \n<p><span>5<\/span> Top-line Results From A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3).” <em>Boehringer Ingelheim<\/em>. Data on file<\/p> \n<p><span>6<\/span> Zimmerman, Tina, et al. “BI 456906: Discovery and preclinical pharmacology of a novel GCGR\/GLP-1R dual agonist with robust anti-obesity efficacy.” <em>Molecular Metabolism<\/em>. Vol. 66, <span class=\"xn-chron\">Dec. 2022<\/span>, p. 101633. doi: 10.1016\/j.molmet.2022.101633.<\/p> \n<p><span>7<\/span> Tan, Tricia M., et al. “Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia.” <em>Diabetes. <\/em>Vol. 62, no. 4, <span class=\"xn-chron\">Mar. 2013<\/span>, pp. 1131-36. doi: 10.2337\/db12-0797<\/p> \n<p><span>8<\/span> Salem, V., et al. “Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.” <em>Diabetes, Obesity and Metabolism<\/em>. Vol. 18, no. 1, <span class=\"xn-chron\">Nov. 2015<\/span>, pp. 72-81. doi: 10.1111\/dom.12585.<\/p> \n<p><span>9<\/span> Shah, Meera, and <span class=\"xn-person\">Adrian Vella<\/span>. “Effects of GLP-1 on appetite and weight.” <em>Reviews in Endocrine and Metabolic Disorders<\/em>. Vol. 15, no. 3, <span class=\"xn-chron\">May 2014<\/span>, pp. 181 – 87. doi: 10.1007\/s11154-014-9289-5.<\/p> \n<p><span>10<\/span> “A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3).” <em>ClinicalTrials.gov<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/rBsNtE3k\" rel=\"nofollow\" target=\"_blank\">classic.clinicaltrials.gov\/ct2\/show\/NCT04771273<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><span>11<\/span> St&aring;l. Per. “Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.” <em>World Journal of Gastroenterology<\/em>. Vol. 21, no. 39, <span class=\"xn-chron\">Jan. 2015<\/span>, p. 11077. doi: 10.3748\/wjg.v21.i39.11077<\/p> \n<p><span>12<\/span> “International NASH Day <span class=\"xn-chron\">June 10<\/span>, 2021.” <em>Global Liver Institute<\/em>. <span class=\"xn-chron\">June 2021<\/span>. <a href=\"https:\/\/t.prnasia.com\/t\/jDOmSIZf\" rel=\"nofollow\" target=\"_blank\">https:\/\/ecpc.org\/wp-content\/uploads\/2021\/09\/IND-report-2021-web.pdf<\/a> Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><span>13<\/span> Ramai, Daryl, et al. “Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease.” <em>Cells<\/em>. Vol. 10, no. 12, <span class=\"xn-chron\">Dec. 2021<\/span>, p. 3401.<span>&nbsp;<\/span>doi: 10.3390\/cells10123401.<\/p> \n<p><sup>14<\/sup> Dyson, Jessica, et al. “Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team.” <em>Journal of Hepatology<\/em>. Vol. 60, no. 1, <span class=\"xn-chron\">Jan. 2014<\/span>, pp. 110–17. doi: 10.1016\/j.jhep.2013.08.011.<\/p> \n<p><sup>15 <\/sup>Adams, Leon A., et al. “Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.” Gut. Vol. 66, no. 6, <span class=\"xn-chron\">Mar. 2017<\/span>, pp.1138-53. doi: 10.1136\/gutjnl-2017-313884<\/p> \n<p><sup>16<\/sup> Estes. Chris, et al. “Modelling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.” <em>Hepatology. <\/em>Vol 67, no. 1, <span class=\"xn-chron\">Dec. 2017<\/span>, pp. 123-33. doi: 10.1002\/hep.29466.<\/p> \n<p><sup>17 <\/sup>Khalil, Amjad, et al. “New Developments and Challenges in Liver Transplantation.” <em>Journal of Clinical Medicine. <\/em>Vol 12, no. 17, <span class=\"xn-chron\">Aug. 2023<\/span>, pp 5586<em>.<\/em> doi: 10.3390\/jcm12175586.<\/p> \n<p><sup>18 <\/sup>Kumar, Rahul, et al. “A practical clinical approach to liver fibrosis.” <em>Singapore Medical Journal. <\/em>Vol. 59, no. 12, <span class=\"xn-chron\">Dec. 2018<\/span>, pp 628-633. doi: 10.11622\/smedj.2018145. PMID: 30631885; PMCID: PMC6301869.<\/p> \n<p><sup>19 <\/sup>Pinzani, Massimo, et al. “Fibrosis in chronic liver diseases: diagnosis and management.” Journal of Hepatology. Vol. 42, no. 1, <span class=\"xn-chron\">April 2005<\/span>, S22-36. doi: 10.1016\/j.jhep.2004.12.008<\/p> \n<p><sup>20 <\/sup>Zhang, Chun-Ye, et al. “Treatment of liver fibrosis: Past, current, and future.” <em>World Journal of Hepatology<\/em>. Vol. 15, no. 6, <span class=\"xn-chron\">June 2023<\/span>, pp. 755-74. doi: 10.4254\/wjh.v15.i6.755.<\/p> \n<p><sup>21 <\/sup>&nbsp;“Boehringer Ingelheim and Zealand Pharma Received FDA Fast Track Designation for Investigational Treatment for NASH.” <em>Boehringer Ingelheim<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/c8q2ghJ1\" rel=\"nofollow\" target=\"_blank\">www.boehringer-ingelheim.com\/us\/press-release\/boehringer-ingelheim-and-zealand-pharma-receive-fda-fast-track-designation<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>22 <\/sup>“List of medicines currently in PRIME scheme.” <em>European Medicines Agency<\/em>. <span class=\"xn-chron\">December 2023<\/span>. <a href=\"https:\/\/t.prnasia.com\/t\/fVNouvYv\" rel=\"nofollow\" target=\"_blank\">www.ema.europa.eu\/en\/documents\/other\/list-medicines-currently-prime-scheme_en.xlsx<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>23 <\/sup>“A Study to Test Whether BI 456906 Helps Chinese People Living With Overweight or Obesity to Lose Weight.” <em>Clinicaltrials.gov<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/XJVxqUIU\" rel=\"nofollow\" target=\"_blank\">clinicaltrials.gov\/study\/NCT06214741<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>24<\/sup>“A Study to Test Whether BI 456906 Helps Japanese People Living With Obesity Disease (SYNCHRONIZE™JP).” <em>Clinicaltrials.gov.<\/em> <a href=\"https:\/\/t.prnasia.com\/t\/H1LVKsEr\" rel=\"nofollow\" target=\"_blank\">clinicaltrials.gov\/study\/NCT06176365<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>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<em>.” The Lancet Gastroenterology &amp; Hepatology. <\/em>Vol. 8, no. 1, <span class=\"xn-chron\">Jan. 2023<\/span>, pp. 20-30. <a href=\"https:\/\/t.prnasia.com\/t\/yeRlBdl2\" rel=\"nofollow\">https:\/\/doi.org\/10.1016\/S2468-1253<\/a>(22)00317-X<\/p> \n<p><sup>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”. <em>Clinicaltrials.gov<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/oH2nZ0wC\" rel=\"nofollow\" target=\"_blank\">https:\/\/clinicaltrials.gov\/study\/NCT06309992<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span>.<\/p> \n<p><sup>27<\/sup> &nbsp;“Nonalcoholic Fatty Liver Disease (NALFD) and NASH.” <em>National Institute of Diabetes and Digestive and Kidney Diseases<\/em>.&nbsp; <a href=\"https:\/\/t.prnasia.com\/t\/6djOs6n5\" rel=\"nofollow\" target=\"_blank\">www.niddk.nih.gov\/health-information\/liver-disease\/nafld-nash<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>28 <\/sup>“Nonalcoholic steatohepatitis (NASH): Symptoms &amp; complications (2023).” <em>American Liver Foundation<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/JvSuq5GY\" rel=\"nofollow\" target=\"_blank\">liverfoundation.org\/liver-diseases\/fatty-liver-disease\/nonalcoholic-steatohepatitis-nash\/<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>29<\/sup> Musso, Giovanni, et al. “Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.” PLoS Medicine. Vol. 11, no. 7, <span class=\"xn-chron\">July 2014<\/span>, p. E1001680. doi: 10.1371\/journal.pmed.1001680.<\/p> \n<p><sup>30<\/sup> <span>Schnell. Oliver, et al. <\/span>“<span>CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.<\/span>” <span>&nbsp;<\/span><span><em>Cardiovascular Diabetology<\/em><\/span><span>. Vol. 23, no. 1, <span class=\"xn-chron\">Mar. 2024<\/span>. doi: 10.1186\/s12933-024-02180-8.<\/span><\/p> \n<p><sup>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.” <em>Hepatology<\/em>. Vol. 41, no. 6, <span class=\"xn-chron\">June 2005<\/span>, pp. 1313-21. doi: 10.1002\/hep.20701.<\/p> \n<p><sup>32 <\/sup>&nbsp;“Non-alcoholic fatty liver disease (NAFLD).” <em>NHS<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/uRF74vZW\" rel=\"nofollow\" target=\"_blank\">www.nhs.uk\/conditions\/non-alcoholic-fatty-liver-disease<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p><sup>33<\/sup> Vanderbeck, Scott, et al. “Automatic quantification of lobular inflammation and hepatocyte ballooning in nonalcoholic fatty liver disease liver biopsies.” <em>Human Pathology.<\/em> Vol. 46, no. 5, <span class=\"xn-chron\">May 2015<\/span>, pp. 767-75. doi: 10.1016\/j.humpath.2015.01.019.<\/p> \n<p><sup>34<\/sup> Caldwell, Stephan, et al. “Hepatocellular ballooning in NASH.” <em>Journal of Hepatology<\/em>. Vol. 53, no. 4, <span class=\"xn-chron\">Oct. 2010<\/span>, pp 719-23. doi: 10.1016\/j.jhep.2010.04.031.<\/p> \n<p><sup>35 <\/sup>“A Study to (1) Compare How&nbsp;BI&nbsp;456906&nbsp;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&nbsp;BI&nbsp;456906.” <em>Clinicaltrials.gov<\/em>. <a href=\"https:\/\/t.prnasia.com\/t\/AzuT1VP4\" rel=\"nofollow\" target=\"_blank\">clinicaltrials.gov\/study\/NCT05296733<\/a>. Accessed <span class=\"xn-chron\">June 2024<\/span><\/p> \n<p>&nbsp;<\/p> \n<p>&nbsp;<\/p>"];
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