協(xié)和麒麟宣布，惠爾金®（莫格利珠單抗）已獲國家藥品監(jiān)督管理局（NMPA）的正式批準(zhǔn)，用于治療既往接受過系統(tǒng)性治療的復(fù)發(fā)或難治性塞扎里綜合征（SS）或晚期（III/IV）蕈樣肉芽腫（MF）成人患者[2]。惠爾金®是中國首 個(gè)也是唯一獲批用于治療SS和MF的靶向CCR4的生物制劑[1]。莫格利珠單抗是一款同類首 創(chuàng)的人源化單克隆抗體（mAb），靶向C-C趨化因子受體4（CCR4）[3]，后者是在SS和MF癌癥細(xì)胞上存在持續(xù)表達(dá)的一種蛋白質(zhì)[4],[5],[6]。一旦惠爾金®與CCR4相結(jié)合，會(huì)在人體免疫系統(tǒng)中激活更多的免疫細(xì)胞，進(jìn)而破壞癌細(xì)胞[7]。

       皮膚T細(xì)胞淋巴瘤（CTCL）屬于罕見型非霍奇金淋巴瘤，SS和MF是CTCL的最常見的兩種亞型[8]，可累及患者皮膚、血液、淋巴結(jié)和內(nèi)臟器官[9]。CTCL較罕見，每10萬人中約有24名患者[10]。歐洲MF的年發(fā)病率約為1/11萬~1/35萬[11]，而SS的年發(fā)病率為1/1000萬[12]。這兩種亞型加起來約占所有CTCL病例的65%[9]?；颊咂毡樯钯|(zhì)量差、誤診率高且晚期缺乏靶向治療藥物，通常會(huì)出現(xiàn)皮損、發(fā)癢、疼痛以及不可預(yù)知的皮膚癥狀，并可能會(huì)導(dǎo)致進(jìn)一步的并發(fā)癥，從而影響他們的預(yù)期壽命[3]，[13]。由于CTCL與濕疹及牛皮癬等常見皮膚病相似[14]，患者平均需要2-7年才能得到確診[15]。晚期患者的預(yù)后明顯更差，約半數(shù)患者（52%）的生存期僅為5年[16]。

       協(xié)和麒麟中國總經(jīng)理李韻表示："惠爾金®于2021年7月獲得藥品審評(píng)中心授予的優(yōu)先審評(píng)資格，現(xiàn)已獲國家藥品監(jiān)督管理局的正式批準(zhǔn)。我們感謝監(jiān)管機(jī)構(gòu)對莫格利珠單抗的加速批準(zhǔn)，這展示了政府為具有高度未被滿足醫(yī)療需求的中國患者帶來創(chuàng)新藥物的決心。這也為中國的塞扎里綜合征和蕈樣肉芽腫患者帶來了希望，他們將能獲得我們這款同類首 創(chuàng)藥物。協(xié)和麒麟通過追求生命科學(xué)和技術(shù)的進(jìn)步來創(chuàng)造新的價(jià)值，我們致力于將更多創(chuàng)新性藥物帶入中國，從而造福廣大中國患者。"

       中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院石遠(yuǎn)凱教授表示："塞扎里綜合征和蕈樣肉芽腫給患者的生活質(zhì)量帶來了沉重的負(fù)擔(dān)。莫格利珠單抗的獲批上市，將為中國這類患者帶來一種全新作用機(jī)制的治療選擇。莫格利珠單抗改善了患者癥狀和生活質(zhì)量，患者的皮膚病變和血液學(xué)指標(biāo)對莫格利珠單抗治療呈現(xiàn)出顯著和持久的效果，中位無進(jìn)展生存期顯著延長。"

       此次獲批是基于MAVORIC研究的結(jié)果。該研究是目前針對SS和MF患者最大規(guī)模的臨床試驗(yàn)[3]。研究結(jié)果表明，惠爾金®組患者的疾病控制時(shí)間是對照藥物伏立諾他組患者的兩倍多（中位無進(jìn)展生存期：7.7個(gè)月 vs 3.1個(gè)月)[3]。在處于各疾病階段的MF/SS患者中，惠爾金®的應(yīng)答率均高于伏立諾他*[3]。惠爾金®和伏立諾他組患者的確認(rèn)總緩解率分別為28%和5%（p<0.001）[3]?；轄柦?reg;的總體耐受性良好，安全性可控[2]，[17]。

       MAVORIC研究還評(píng)估了患者報(bào)告的癥狀體驗(yàn)和生活質(zhì)量（QoL）。結(jié)果表明，與接受伏立諾他治療的患者相比，接受惠爾金®的患者在癥狀、情緒、功能和整體生活質(zhì)量方面均得到改善，體現(xiàn)在大部分功能和癥狀領(lǐng)域?？傮w而言，這些研究結(jié)果表明，與伏立諾他組相比，惠爾金®組患者的疾病及癌癥特異性狀況相關(guān)生活質(zhì)量和總生活質(zhì)量均得到改善，同時(shí)生活質(zhì)量快速惡化的風(fēng)險(xiǎn)呈具有統(tǒng)計(jì)學(xué)意義的顯著降低[18]。

       關(guān)于惠爾金®（莫格利珠單抗）

       惠爾金®是一款同類首 創(chuàng)人源化單克隆抗體（mAb），旨在與C-C趨化因子受體4（CCR4）相結(jié)合。惠爾金®與CCR4結(jié)合后，會(huì)在人體免疫系統(tǒng)中激活更多的免疫細(xì)胞，進(jìn)而破壞癌細(xì)胞[7]?；轄柦?reg;使用協(xié)和麒麟專有的POTELLIGENT®技術(shù)，可增強(qiáng)人體對治療的自然免疫反應(yīng)，從而提高對癌細(xì)胞的殺傷力。FDA已授予惠爾金®突破性療法和孤兒藥認(rèn)定[19],[20]。此外，惠爾金®還于2016年被歐盟委員會(huì)（EC）授予孤兒藥認(rèn)定[21]?；轄柦?reg;是首 個(gè)也是唯一在中國和世界其他地區(qū)獲批的靶向CCR4的生物制劑[22]。

       *伏立諾他是美國FDA批準(zhǔn)用于治療蕈樣肉芽腫和塞扎里綜合征的藥物，目前尚未在中國獲批

       參考文獻(xiàn)

       [1] Until July 2022, the data source: Ding Xiang Yuan database.

       [2] Placeholder (To be updated with NMPA approval news release)

       [3] Kim YH, Bagot M, Pinter-Brown L, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192-1204.

       [4] Ferenczi K, Fuhlbrigge RC, Pinkus J, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405-10.

       [5] Yoshie O, et al. Frequent Expression of CCR4 in Adult T-Cell Leukemia and Human T-cell Leukemia Virus Type 1-transformed T cells. Blood. 2002;99(5):1505-11.

       [6] Ishida T, et al. Clinical Significance of CCR4 Expression in Adult T-cell Leukemia/Lymphoma: Its Close Association With Skin Involvement and Unfavorable Outcome. Clin Cancer Res. 2003;9:3625-34.

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       [8] Willemze R, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-1714.

       [9] Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713-22.

       [10] Orphanet: Prevalence and incidence of rare diseases: Bibliographic data. Available from: https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf. Last accessed: June 2020.

       [11] Orphanet: Mycosis Fungoides. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2584. Last Accessed: June 2020.

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       [13] Haun P, et al. Fast Facts : Diagnosing Cutaneous T-Cell Lymphoma. Karger Publishing. 2016.

       [14] Cutaneous Lymphoma Foundation, Lymphoma Action and Lymphoma Coalition Europe. Cutaneous lymphoma – a patient's guide. 2019. Available from: https://lymphoma-action.org.uk/sites/default/files/media/documents/2019-06/Cutaneous%20lymphoma%20-%20patient%26%23039%3Bs%20guide%20-%20English%20language%20source%20document%20-%20final%20version%20for%20publication%20-%20April%202019.pdf. Last accessed: June 2020.

       [15] CL Foundation: A Patient's Guide. Available from: https://www.clfoundation.org/sites/default/files/2018-04/a_patients_guide.pdf. Last Accessed: 18 November 2019.

       [16] Scarisbrick JJ, Prince M, Vermeer MH, et al. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol. 2015;33(32):3766-3773.

       [17] Kim YH, Bagot M, Zinzani PL et al. Safety of Mogamulizumab in Mycosis Fungoides and Sézary Syndrome: Final Results from the Phase 3 Mavoric Study. Blood. 2019;134 (1):5300.

       [18] Clin Lymphoma Myeloma Leuk. 2021 Feb; 21(2):97-105

       [19] Search Orphan Drug Designations and Approvals (fda.gov). Available from https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=322010. Last accessed: July 2022.

       [20] FDA approves treatment for two rare types of non-Hodgkin lymphoma. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-two-rare-types-non-hodgkin-lymphoma. Last accessed: July 2022.

       [21] EU/3/16/1756: Orphan designation for the treatment of cutaneous T-cell lymphoma. Available from: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3161756. Last accessed: July 2022.