复宏汉霖自主研发的汉达远（阿达木单抗注射液）新适应症补充申请获NMPA受理

转自：复星医药

近日，复宏汉霖（2696.HK）宣布公司自主开发的汉达远®（阿达木单抗注射液）补充申请获国家药品监督管理局（NMPA）受理，用于多关节型幼年特发性关节炎、儿童斑块状银屑病等自身免疫疾病的治疗，有望为儿童患者及其家庭带来新希望。截至目前，该产品已获批治疗类风湿关节炎、强直性脊柱炎、银屑病、葡萄膜炎4项适应症。

自身免疫疾病是一类由于机体免疫系统攻击自身器官或组织而造成的疾病[1]，据估计，全球约有7.6%-9.4%的人群患有各种类型的自身免疫性疾病[2]，目前自身免疫性疾病难以治愈，一旦患病，大多数患者需要长期甚至终身服药，且部分疾病病情凶险，严重影响患者生活质量，威胁生命安全，给患者造成巨大的负担。肿瘤坏死因子-α(TNF-α)是诱发炎症和其他免疫反应的主要细胞因子之一，在多种自身免疫疾病的发病过程中具有关键性的作用[3]，现已证明，类风湿性关节炎、银屑病、强直性脊柱炎等多种自身免疫性疾病与TNF-α密切相关。阿达木单抗作为全人源化抗TNF-α单抗，可特异性地与TNF-α结合，阻断其与TNF受体p55和p75的相互作用，从而有效阻断TNF-α介导的一系列致炎作用，对多种自身免疫疾病起到有效持久的控制。凭借在自免疾病领域良好的疗效和安全性，阿达木单抗迅速取代糖皮质激素、非甾体抗炎药成为临床优选，并获得美国风湿病学会(ACR)编撰的《类风湿关节炎诊疗指南》、美国皮肤病学会(AAD)联合国家银屑病基金会(NPF)共同发布的《AAD-NPF银屑病生物治疗指南》等多个全球权威自免类诊疗指南的推荐。

汉达远®是复宏汉霖按照《生物类似药研发与评价技术指导原则（试行）》自主开发的单抗生物类似药，也是公司首款治疗自身免疫疾病的产品，并获得“十二五”、“十三五”国家科技重大专项（重大新药创制）立项支持。汉达远®以原研阿达木单抗为参照药，与原研药进行了多项头对头比对研究，包括药学比对研究、非临床比对研究和临床比对研究，研究结果证明汉达远®在质量、安全性和有效性等方面与原研药高度相似。2020年12月，汉达远®获国家药监局批准上市，用于治疗类风湿关节炎、强直性脊柱炎和银屑病适应症。此外，复宏汉霖还向国家药监局申请产品适应症外推增加葡萄膜炎，并于2021年3月获批，为眼科治疗带来更多用药选择。

目前，汉达远®在国内的商业销售由复星医药旗下万邦医药负责，该公司建有相当规模的风湿免疫事业部和面向广阔市场的混线销售团队，在自免疾病治疗领域具有丰富的商业化经验。截至目前，汉达远®已正式纳入国家医保目录，并完成了29个省份的招标挂网和所有省份医保准入。随着汉达远®逐步新增更多适应症，复宏汉霖将与万邦医药深化合作，在自身免疫疾病领域持续深耕，向着“让每一位自免患者应治尽治”的宏愿迈进。

未来，复宏汉霖也将继续秉持“以患者为中心”的理念，以创新研发为核心驱动力，持续探索，为患者提供更多优质、可负担的生物药，推动中国自身免疫性疾病患者获益最大化。

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在国际上市2款产品，19项适应症获批，7个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，上海徐汇基地和松江基地（一）均已获得中国和欧盟GMP认证。

复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。

HenliusAdalimumabBiosimilarReceivedsNDAAcceptanceNotification fromtheNMPA

Shanghai,China,29th February2024–ShanghaiHenliusBiotech,Inc.(2696.HK)announcedthatthesupplementalnewdrugapplications(sNDAs)ofitsadalimumabbiosimilarHANDAYUAN forthetreatmentof polyarticularjuvenileidiopathicarthritis，pediatricplaquepsoriasisandotherindicationshavebeenacceptedbytheNationalMedicalProductsAdministration(NMPA)，bringingnewhopetopediatricpatientsandtheirfamilies.Asofnow,HANDAYUANhasbeenapprovedforthetreatmentofrheumatoidarthritis,ankylosingspondylitis,plaquepsoriasis  anduveitis.

Autoimmunediseasesareagroupofdiseasescausedbythebody’simmunesystemattackingitsownorgansortissues[1].Itisestimatedthatapproximately7.6%-9.4%oftheglobalpopulationsuffersfromvarioustypesofautoimmunediseases[2].Currently,autoimmunediseasesaredifficulttocure,andonceitoccurs,mostpatientsneedlong-termtolifelongmedication.Someautoimmunediseasesareparticularlydangerousandseverelyaffectthequalityoflifeofpatients,posingathreattotheirlivesandcausingsignificantburden.Tumornecrosisfactor-α(TNF-α)isoneofthemajorcytokinesthatinduceinflammationandotherimmuneresponses.Itplaysakeyroleinthepathogenesisofavarietyofautoimmunediseases[3].Ithasbeenproventhatmanyautoimmunediseasessuchasrheumatoidarthritis,psoriasisandankylosingspondylitisarecloselyrelatedtoTNF-α.Adalimumab,ahumanizedanti-TNF-αmonoclonalantibody,canspecificallybindtoTNF-αandblockitsinteractionwithTNFreceptorsp55andp75,therebyeffectivelyinhibitingtheactivityofTNF-αandprovidingeffectiveandlong-lastingcontrolofavarietyofautoimmunediseases.Withitsgoodefficacyandsafetyinthetreatmentofautoimmunediseases,adalimumabhasquicklyreplacedglucocorticoidsandnonsteroidalanti-inflammatorydrugsasoneofprimechoicesinclinicalpractice.Ithasreceivedrecommendationsfrommanyglobalauthoritativeclinicaltreatmentguidelinesforautoimmunediseases,includingtheAmericanCollegeofRheumatologyGuidelinefortheTreatmentofRheumatoidArthritisandtheAAD-NPFGuidelinesfortheTreatmentofPsoriasiswithBiologics.

HANDAYUANisamonoclonalantibodybiosimilardevelopedbyHenliusinaccordancewiththeTechnicalGuidelinesforR&DandEvaluationofBiosimilars(Trial) and isalsoHenlius‘firstproductapprovedforthetreatmentofautoimmunediseases. ItreceivedsupportfromtheNationalScienceandTechnologyMajorProject(China-MajorNewDrugResearch&DevelopmentProject)during the12th&13thFive-YearPlans. Ontheotherhand,HANDAYUANhastakenmultiplehead-to-headcomparisonstudiestotheoriginatoradalimumab.Resultsfromthepharmaceuticalcomparisonstudies,non-clinicalstudiesandclinicalstudiesshowedthatHANDAYUANishighlysimilartotheoriginatoradalimumabintermsofquality,safety,andefficacy. InDecember2020,HANDAYUANwasapprovedbytheNMPAforthetreatmentofrheumatoidarthritis,ankylosingspondylitis,andplaque psoriasis.Inaddition,HenliusalsosubmittedthesNDAforthetreatmentofuveitisandwasapprovedinMarch2021,providinganewtreatmentoptionforophthalmology.

Currently,thecommercializationofHANDAYUANinChinaishandledbyWanbangPharmawhichhasasizeabledepartmentofrheumatologyandimmunizationandamixed-linesalesteamservingthebroadmarket,withsuccessfulcommercializationexperienceinautoimmunediseases.Uptodate,HANDAYUANhasbeenincludedinthenationalmedicalinsurancecatalogue.Ithascompletedtenderingprocessontheprocurementplatformin29provincesandisincludedintothemedicalinsuranceprocurementplatforminallprovincesinChinesemainland.AsmoreindicationssubmittedandapprovedofHANDAYUAN,HenliuswilldeepenthecooperationwithWanbangPharmatofurtherpromoteitscommercializationtofulfilleverypatient’sneeds.

Lookingforward,Henliuswilladheretotheprincipleofpatientcentricityandtakeinnovationasthedrivingforcetoexploreandprovidepatientswithmorehigh-qualityandaffordablebiologicalmedicinesandmaximizethebenefitsforChinesepatientswithautoimmunediseases.

参考文献

[1]GoodnowCC.Multisteppathogenesisofautoimmunedisease[J].Cell,2007,130(1):25-35.  

[2]CooperGS,BynumMLK,SomersEC.Recentinsightsintheepidemiologyofautoimmunediseases:improvedprevalenceestimatesandunderstandingofclusteringofdiseases[J].Journalofautoimmunity,2009,33(3-4):197-207.

[3]SilvaLCR,OrtigosaLCM,BenardG.Anti-TNF-αagentsinthetreatmentofimmune-mediatedinflammatorydiseases:mechanismsofactionandpitfalls[J].Immunotherapy,2010,2(6):817-833.

AboutHenlius

Henlius(2696.HK)isaglobalbiopharmaceuticalcompanywiththevisiontoofferhigh-quality,affordable,andinnovativebiologicmedicinesforpatientsworldwidewithafocusononcology,autoimmunediseases,andophthalmicdiseases.Uptodate,5productshavebeenlaunchedinChina,2havebeenapprovedformarketinginoverseasmarkets,19indicationsareapprovedworldwide,and7 marketingapplicationshavebeenacceptedforreviewinChina,theU.S.,andtheEU,respectively.Sinceitsinceptionin2010,Henliushasbuiltanintegratedbiopharmaceuticalplatformwithcorecapabilitiesofhigh-efficiencyandinnovationembeddedthroughoutthewholeproductlifecycleincludingR&D,manufacturingandcommercialization.IthasestablishedglobalinnovationcentersandShanghai-basedmanufacturingfacilitiesinlinewithglobalGoodManufacturingPractice(GMP),includingXuhuiFacilityandSongjiangFirstPlant,bothcertificatedbyChinaandtheEUGMP.

Henliushaspro-activelybuiltadiversifiedandhigh-qualityproductpipelinecoveringover20innovativemonoclonalantibodies(mAbs)andhascontinuedtoexploreimmuno-oncologycombinationtherapieswithproprietaryHANSIZHUANG(anti-PD-1mAb)asbackbone.ApartfromthelaunchedproductsHANLIKANG(rituximab),thefirstChina-developedbiosimilar,HANQUYOU(trastuzumabforinjection,tradenameinEurope:Zercepac®;tradenamesinAustralia:Tuzucip® andTrastucip®),thefirstChina-developedmAbbiosimilarapprovedbothinChinaandEurope,HANDAYUAN(adalimumab)andHANBEITAI(bevacizumab),theinnovativeproductHANSIZHUANGhasbeenapprovedbytheNMPAforthetreatmentofMSI-Hsolidtumors,squamousnon-smallcelllungcancer(sqNSCLC)andextensive-stagesmallcelllungcancer(ES-SCLC),andesophagealsquamouscellcarcinoma(ESCC),makingittheworld'sfirstanti-PD-1mAbforthefirst-linetreatmentofSCLC.What'smore,Henliushasconductedover30clinicalstudiesfor16products,expandingitspresenceinmajormarketsaswellasemergingmarkets.