鍏充簬浠ｈ阿鍔熻兘闅滅鐩稿叧鑴傝偑鎬ц倽鐐庯紙<\/strong>MASH<\/strong>锛�<\/strong><\/p> \n

MASH鏄竴绉嶇敱鑲濊剰涓剛鑲爢绉紩璧风殑鎱㈡€ц繘琛屾€ц倽鐥咃紝^{13,27<\/sup>涔熸槸浠ｈ阿鍔熻兘闅滅鐩稿叧鑴傝偑鎬ц倽鐥咃紙MASLD锛変腑涓€绉嶆洿涓轰弗閲嶇殑绫诲瀷銆�28<\/sup>鏍规嵁缇庡浗鐨勭爺绌堕娴嬶紝浠�2015骞磋嚦2030骞达紝MASH鐨勭梾渚嬫暟灏嗘縺澧�63%锛屼粠1650涓囦緥鏀€鍗囪嚦2700涓囦緥銆�16<\/sup> MASH涓庡績琛€绠°€佽偩鑴忓強澶氱浠ｈ阿鐤剧梾涔嬮棿瀛樺湪鐫€瀵嗗垏鍏宠仈銆�29,30<\/sup>鎹粺璁★紝楂樿揪34%鐨勮偉鑳栨偅鑰呭悓鏃舵偅鏈塎ASH銆�25<\/sup><\/p> \n}

MASH 涓ラ噸绋嬪害浣跨敤F0鑷矲4鑼冨洿鍐呯殑绛夌骇杩涜璇勪及锛岃瘎浼扮氦缁村寲锛堢枻鐥曪級鐨勬按骞筹細^{31<\/sup><\/p> \n}

\n
• F0-F1锛氳〃绀烘棤绾ょ淮鍖栨垨杞诲害绾ょ淮鍖�<\/li> \n
• F2-F3锛氳〃绀轰腑搴︽垨鏅氭湡绾ょ淮鍖�<\/li> \n
• F4锛氳〃绀鸿倽纭寲<\/li> \n<\/ul> \n

  鍏充簬鏈涓村簥璇曢獙锛�<\/strong>NCT04771273<\/strong>锛�<\/strong><\/p> \n

  杩欐槸涓€椤笽I鏈熴€侀殢鏈恒€佸弻鐩层€佸畨鎱板墏瀵圭収鐨勫墏閲忔帰绱㈡€ц瘯楠岋紝鍏辩撼鍏ヤ簡295鍚嶅彈璇曡€呫€傝璇曢獙鏃ㄥ湪璇勪及姣忓懆鐨笅娉ㄥ皠survodutide瀵逛即鏈夋垨鏈即鏈�2鍨嬬硸灏跨梾鐨凪ASH鍙婏紙F1锛孎2锛孎3鏈燂級绾ょ淮鍖栨垚浜烘偅鑰呯殑娌荤枟鏁堟灉銆�^{10<\/sup><\/p> \n}

  鏈涓村簥璇曢獙鐨勪富瑕佺粓鐐规槸娌荤枟48鍛ㄥ悗锛岃揪鍒癕ASH缁勭粐瀛︽敼鍠勪笖绾ょ淮鍖栨棤鎭跺寲鐨勫彈璇曡€呯櫨鍒嗘瘮銆�^{10<\/sup> MASH鐨勭粍缁囧鏀瑰杽瀹氫箟涓洪潪閰掔簿鎬ц剛鑲倽鐥呮椿鍔ㄦ€ц瘎鍒嗭紙NAS锛夐檷浣� 鈮� 2鍒嗭紙鎬诲垎涓�0 - 8鍒嗭級锛屽寘鎷琋ASH浜氳瘎鍒嗭紙灏忓彾鐐庣棁鎴栨皵鐞冩牱鍙橈級闄嶄綆 鈮� 1鍒嗭紝鍚屾椂纭繚绾ょ淮鍖栧垎鏈熶笉澧炲姞銆�10<\/sup> NAS璇勫垎浠ｈ〃浜嗚剛鑲彉鎬э紙鑲濊剛鑲Н鑱�32<\/sup>锛夈€佸皬鍙剁値鐥囷紙鐐庣棁缁嗚優33<\/sup>锛夊拰姘旂悆鏍峰彉锛堜竴绉嶈倽缁嗚優鍙樻€�34<\/sup>锛夌殑寰楀垎鎬诲拰銆�<\/p> \n}

  娆¤缁撳眬鍖呮嫭锛�^{10<\/sup><\/p> \n}

  \n
  • 娌荤枟48鍛ㄥ悗锛岃倽鑴忚剛鑲惈閲忕浉杈冧簬鍩虹嚎鐩稿鍑忓皯鑷冲皯30%<\/li> \n
  • 娌荤枟48鍛ㄥ悗锛岃倽鑴忚剛鑲惈閲忕浉杈冧簬鍩虹嚎鐨勭粷瀵瑰拰鐩稿鍙樺寲<\/li> \n
  • 娌荤枟48鍛ㄥ悗锛岀氦缁村寲绋嬪害鑷冲皯鍑忓皯涓€涓垎鏈熺殑锛堢氦缁村寲鏀瑰杽鐨勫畾涔夛級<\/li> \n
  • 娌荤枟48鍛ㄥ悗锛孨AS鎬诲垎鐩歌緝浜庡熀绾跨殑缁濆鍙樺寲<\/li> \n<\/ul> \n

    鏈璇曢獙閲囩敤鍓傞噺閫掑鐨勮璁★紝鍖呮嫭2.4 mg銆�4.8 mg鍜�6.0 mg涓変釜娌荤枟缁勶紝鍓傞噺閫掑闃舵鎸佺画24鍛紝闅忓悗杩涘叆涓烘湡24鍛ㄧ殑鍓傞噺缁存寔闃舵銆�^{10<\/sup><\/p> \n}

    鍏充簬<\/strong>Survodutide<\/strong>锛�<\/strong>BI456906<\/strong>锛�<\/strong><\/p> \n

    Survodutide鏄竴绉嶈儼楂樿绯栫礌鍙椾綋\/鑳伴珮琛€绯栫礌鏍疯偨-1鍙椾綋锛圙CGR\/GLP-1R锛夊弻閲嶆縺鍔ㄥ墏锛屽彲鍚屾椂婵€娲昏儼楂樿绯栫礌鍙椾綋鍜孏LP-1鍙椾綋锛岃繖瀵逛簬鎺у埗浠ｈ阿鍔熻兘鑷冲叧閲嶈銆�^{6<\/sup><\/p> \n}

    Zealand Pharma鎺堟潈鍕冩灄鏍兼鏍肩堪鍏ㄦ潈璐熻矗survodutide鐨勫叏鐞冨紑鍙戜笌鍟嗕笟鍖栵紝淇濈暀浜嗗湪鍖楁甯傚満鐨勮仈鍚堟帹骞挎潈鐩娿€係urvodutide鏄媰鏋楁牸娈锋牸缈板湪浠ｈ阿蹇冭偩鐤剧梾棰嗗煙鐮斿彂缁勫悎鐨勭粍鎴愰儴鍒嗐€�<\/p> \n

    2021骞�5鏈堬紝survodutide鐢ㄤ簬MASH鍜岀氦缁村寲娌荤枟鎴愬姛鑾峰緱缇庡浗FDA鐨勫揩閫熼€氶亾璁ゅ畾銆�^{21 <\/sup>23骞�11鏈堬紝EMA灏嗗叾绾冲叆PRIME璁″垝銆�22<\/sup><\/p> \n}

    鍕冩灄鏍奸拡杩樺survodutide鍦ㄨ倽纭寲锛團4锛夊強涓嶅悓绋嬪害鑲濆姛鑳介殰纰嶄汉缇や腑杩涜浜嗕竴椤瑰垎涓ら儴鍒嗙殑I鏈熻瘯楠屻€�^{35<\/sup>绗�1閮ㄥ垎璇曢獙鏃ㄥ湪鎺㈢┒鑲濈‖鍖栵紙F4锛変互鍙婁笉鍚岀▼搴﹁倽鍔熻兘闅滅瀵箂urvodutide鍦ㄤ汉浣撳唴鍚告敹鏂瑰紡鐨勫奖鍝嶃€傜2閮ㄥ垎璇曢獙鍒欐棬鍦ㄦ帰绌跺湪鑲濈‖鍖栵紙F4锛夊強涓嶅悓绋嬪害鑲濆姛鑳介殰纰嶇殑瓒呴噸鍜岃偉鑳栦汉缇や腑锛宻urvodutide娌荤枟28鍛ㄧ殑鑰愬彈鎬с€�<\/p> \n}

    Survodutide杩樻鍦ㄤ簲椤归拡瀵硅秴閲嶅拰鑲ヨ儢鐥囨偅鑰呯殑III鏈熺爺绌朵腑鎺ュ彈璇勪及銆�^{2<\/sup>,23,24<\/sup>鍏朵腑锛孲YNCHRONIZE-1鍜孲YNCHRONIZE-2鐮旂┒鍒嗗埆閽堝鏈夊悎骞剁棁浣嗕笉浼村拰浼存湁2鍨嬬硸灏跨梾鐨勪簹缁勬偅鑰呫€�2<\/sup> SYNCHRONIZE-CVOT鐮旂┒鍒欓拡瀵逛即鏈夊績琛€绠＄柧鐥呫€佹參鎬ц偩鐥呮垨蹇冭绠＄柧鐥呴闄╁洜绱犵殑浜氱粍浜虹兢銆�2<\/sup>鍦ㄥ湴鍩熸€х爺绌朵腑锛屾棩鏈殑SYNCHRONIZE-JP鍜屼腑鍥界殑SYNCHRONIZE-CN鐮旂┒姝ｈ嚧鍔涗簬鎺㈢储survodutide鍦ㄨ偉鑳栫棁鎮ｈ€呬簹浜虹兢涓殑娌荤枟鏁堟灉銆�23,24 <\/sup>SYNCHRONIZE-JP鐮旂┒鎺㈢储survodutide涓庡畨鎱板墏鐩告瘮锛岃倽鑴忚剛鑲惈閲忎粠鍩虹嚎鍒扮76鍛ㄧ殑鐩稿鍙樺寲锛屾涓哄叧閿瑕佺粓鐐广€�24<\/sup><\/p> \n}

    Reference锛�<\/span><\/strong><\/p> \n

    1<\/span> Sanyal, Arun J. "<\/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鈥�. Oral presentation at European Association for the Study of the Liver Congress, Milan, Italy<\/span>. 7June 2024. Abstract #LB117, presentation #GS-006.<\/span><\/p> \n

    2<\/span> 鈥淧hase III studies to investigate survodutide for people living with obesity and overweight, with and without diabetes, cardiovascular disease and<\/span> chronic kidney disease.鈥� <\/span>Boehringer Ingelheim<\/span><\/em>. <\/span>www.boehringer-ingelheim.com\/phase-3-studies-survodutide-obesity-and-overweight<\/span><\/a>. <\/span>Accessed June 2024<\/span><\/span><\/p> \n

    3<\/span> Sanyal, Arun J., et al. 鈥淧rospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.鈥� The New England Journal of Medicine. Vol. 385, no. 17, 2021, pp. 1559-1569. doi: 10.1056\/NEJMoa2029349<\/span><\/p> \n

    4<\/span> Sanyal, Arun J., et al. 鈥淎 Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.鈥� The New England Journal of Medicine. <\/em>June 2024. doi: 10.1056\/NEJMoa2401755<\/span><\/p> \n

    5<\/span> Top-line Results From A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3).鈥� Boehringer Ingelheim<\/em>. Data on file<\/p> \n

    6<\/span> Zimmerman, Tina, et al. 鈥淏I 456906: Discovery and preclinical pharmacology of a novel GCGR\/GLP-1R dual agonist with robust anti-obesity efficacy.鈥� Molecular Metabolism<\/em>. Vol. 66, Dec. 2022<\/span>, p. 101633. doi: 10.1016\/j.molmet.2022.101633.<\/p> \n

    7<\/span> Tan, Tricia M., et al. 鈥淐oadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia.鈥� Diabetes. <\/em>Vol. 62, no. 4, Mar. 2013<\/span>, pp. 1131-36. doi: 10.2337\/db12-0797<\/p> \n

    8<\/span> Salem, V., et al. 鈥淕lucagon increases energy expenditure independently of brown adipose tissue activation in humans.鈥� Diabetes, Obesity and Metabolism<\/em>. Vol. 18, no. 1, Nov. 2015<\/span>, pp. 72-81. doi: 10.1111\/dom.12585.<\/p> \n

    9<\/span> Shah, Meera, and Adrian Vella<\/span>. 鈥淓ffects of GLP-1 on appetite and weight.鈥� Reviews in Endocrine and Metabolic Disorders<\/em>. Vol. 15, no. 3, May 2014<\/span>, pp. 181 鈥� 87. doi: 10.1007\/s11154-014-9289-5.<\/p> \n

    10<\/span> 鈥淎 Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3).鈥� ClinicalTrials.gov<\/em>. classic.clinicaltrials.gov\/ct2\/show\/NCT04771273<\/a>. Accessed June 2024<\/span><\/p> \n

    11<\/span> Stål. Per. 鈥淟iver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.鈥� World Journal of Gastroenterology<\/em>. Vol. 21, no. 39, Jan. 2015<\/span>, p. 11077. doi: 10.3748\/wjg.v21.i39.11077<\/p> \n

    12<\/span> 鈥淚nternational NASH Day June 10<\/span>, 2021.鈥� Global Liver Institute<\/em>. June 2021<\/span>. https:\/\/ecpc.org\/wp-content\/uploads\/2021\/09\/IND-report-2021-web.pdf<\/a> Accessed June 2024<\/span><\/p> \n

    13<\/span> Ramai, Daryl, et al. 鈥淧rogressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease.鈥� Cells<\/em>. Vol. 10, no. 12, Dec. 2021<\/span>, p. 3401. <\/span>doi: 10.3390\/cells10123401.<\/p> \n

    ^{14<\/sup> Dyson, Jessica, et al. 鈥淗epatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team.鈥� Journal of Hepatology<\/em>. Vol. 60, no. 1, Jan. 2014<\/span>, pp. 110鈥�17. doi: 10.1016\/j.jhep.2013.08.011.<\/p> \n}

    ^{15 <\/sup>Adams, Leon A., et al. 鈥淣on-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.鈥� Gut. Vol. 66, no. 6, Mar. 2017<\/span>, pp.1138-53. doi: 10.1136\/gutjnl-2017-313884<\/p> \n}

    ^{16<\/sup> Estes. Chris, et al. 鈥淢odelling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.鈥� Hepatology. <\/em>Vol 67, no. 1, Dec. 2017<\/span>, pp. 123-33. doi: 10.1002\/hep.29466.<\/p> \n}

    ^{17 <\/sup>Khalil, Amjad, et al. 鈥淣ew Developments and Challenges in Liver Transplantation.鈥� Journal of Clinical Medicine. <\/em>Vol 12, no. 17, Aug. 2023<\/span>, pp 5586.<\/em> doi: 10.3390\/jcm12175586.<\/p> \n}

    ^{18 <\/sup>Kumar, Rahul, et al. 鈥淎 practical clinical approach to liver fibrosis.鈥� Singapore Medical Journal. <\/em>Vol. 59, no. 12, Dec. 2018<\/span>, pp 628-633. doi: 10.11622\/smedj.2018145. PMID: 30631885; PMCID: PMC6301869.<\/p> \n}

    ^{19 <\/sup>Pinzani, Massimo, et al. 鈥淔ibrosis in chronic liver diseases: diagnosis and management.鈥� Journal of Hepatology. Vol. 42, no. 1, April 2005<\/span>, S22-36. doi: 10.1016\/j.jhep.2004.12.008<\/p> \n}

    ^{20 <\/sup>Zhang, Chun-Ye, et al. 鈥淭reatment of liver fibrosis: Past, current, and future.鈥� World Journal of Hepatology<\/em>. Vol. 15, no. 6, June 2023<\/span>, pp. 755-74. doi: 10.4254\/wjh.v15.i6.755.<\/p> \n}

    ^{21 <\/sup> 鈥淏oehringer Ingelheim and Zealand Pharma Received FDA Fast Track Designation for Investigational Treatment for NASH.鈥� 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>鈥淟ist of medicines currently in PRIME scheme.鈥� 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>鈥淎 Study to Test Whether BI 456906 Helps Chinese People Living With Overweight or Obesity to Lose Weight.鈥� Clinicaltrials.gov<\/em>.} clinicaltrials.gov\/study\/NCT06214741<\/a>. Accessed June 2024<\/span><\/p> \n

    ^{24<\/sup>鈥淎 Study to Test Whether BI 456906 Helps Japanese People Living With Obesity Disease (SYNCHRONIZE鈩P).鈥� Clinicaltrials.gov.<\/em>} clinicaltrials.gov\/study\/NCT06176365<\/a>. Accessed June 2024<\/span><\/p> \n

    ^{25<\/sup> Quek, Jingxuan, et al. 鈥滸lobal prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis.鈥� 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> 鈥淎 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鈥�. Clinicaltrials.gov<\/em>.} https:\/\/clinicaltrials.gov\/study\/NCT06309992<\/a>. Accessed June 2024<\/span>.<\/p> \n

    ^{27<\/sup>  鈥淣onalcoholic Fatty Liver Disease (NALFD) and NASH.鈥� National Institute of Diabetes and Digestive and Kidney Diseases<\/em>.}  www.niddk.nih.gov\/health-information\/liver-disease\/nafld-nash<\/a>. Accessed June 2024<\/span><\/p> \n

    ^{28 <\/sup>鈥淣onalcoholic steatohepatitis (NASH): Symptoms & complications (2023).鈥� American Liver Foundation<\/em>.} liverfoundation.org\/liver-diseases\/fatty-liver-disease\/nonalcoholic-steatohepatitis-nash\/<\/a>. Accessed June 2024<\/span><\/p> \n

    ^{29<\/sup> Musso, Giovanni, et al. 鈥淎ssociation of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.鈥� PLoS Medicine. Vol. 11, no. 7, July 2014<\/span>, p. E1001680. doi: 10.1371\/journal.pmed.1001680.<\/p> \n}

    ^{30<\/sup> Schnell. Oliver, et al. <\/span>鈥�CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.<\/span>鈥�  <\/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. 鈥淣onalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.鈥� Hepatology<\/em>. Vol. 41, no. 6, June 2005<\/span>, pp. 1313-21. doi: 10.1002\/hep.20701.<\/p> \n}

    ^{32 <\/sup> 鈥淣on-alcoholic fatty liver disease (NAFLD).鈥� NHS<\/em>.} www.nhs.uk\/conditions\/non-alcoholic-fatty-liver-disease<\/a>. Accessed June 2024<\/span><\/p> \n

    ^{33<\/sup> Vanderbeck, Scott, et al. 鈥淎utomatic quantification of lobular inflammation and hepatocyte ballooning in nonalcoholic fatty liver disease liver biopsies.鈥� 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. 鈥淗epatocellular ballooning in NASH.鈥� 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>鈥淎 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.鈥� Clinicaltrials.gov<\/em>.} clinicaltrials.gov\/study\/NCT05296733<\/a>. Accessed June 2024<\/span><\/p> \n

     <\/p> \n

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