Antibodies to watch in 2019
Antibodies to watch in 2019
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DOI：
10.1080/19420862.2018.1556465
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发表时间：
2019-02-17
期刊：
影响因子：
5.3
通讯作者：
Reichert, Janice M.
中科院分区：
文献类型：
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作者：
Kaplon, Helene;Reichert, Janice M.
在过去的10年中，每年的“抗体观察”文章提供了抗体治疗后期开发中的关键事件的更新，例如首次监管审查或批准，这些事件发生在出版前一年或预计将在出版当年发生。为了纪念该系列文章发表10周年，并庆祝2018年诺贝尔化学奖和生理学或医学奖，这些奖项是为与抗体治疗研究和开发高度相关的工作而颁发的，我们扩大了所提供数据的范围，以包括抗体治疗的所有商业临床开发概述和这类分子的批准成功率。我们的数据表明：1）抗体治疗剂正在进入临床研究，并以创纪录的数量获得批准; 2）商业管道是稳健的，在各个临床阶段有超过570种抗体治疗剂，包括62种处于后期临床研究中; 3）1期至批准成功率是有利的，范围从17- 25%，取决于治疗领域（癌症与非癌症）。2018年，抗体数量创纪录（12）（erenumab（Aimovig）、fremanezumab（Ajovy）、galcanezumab（Emgality），burosumab（Crysvita），lanadelumab（Takhzyro）、caplacizumab（Cablivi）、mogamulizumab（Poteligeo），moxetumomab pasudodox（Lumoxiti）、cemiplimab（Libtayo）、ibalizumab（Trogarzo），tildrakizumab（Ilumetri，Ilumya），emapalumab（Gamifant））在欧盟（EU）或美国（US）首次获得批准。截至2018年11月，4种抗体治疗药物（sacituzumab govitecan、ravulizumab、risankizumab、romosozumab）正在考虑在欧盟或美国获得首次上市批准，另外3种由中国公司开发的抗体治疗药物（tislelizumab、sintilimab、camrelizumab）正在中国进行监管审查。此外，我们的数据显示，到2018年底，3种候选产品（leronlimab、brolucizumab、polatuzumab vedotin）可能进入监管审查，2019年至少有12种（eptinezumab、teprotumumab、crizanlizumab、satralizumab、tanezumab、isatuximab、spartalizumab、MOR 208、oportuzumab monatox、TSR-042、enfortumab vedotin、ublituximab）可能进入监管审查。最后，我们发现大约一半（33个中的18个）的晚期癌症抗体治疗药物是免疫检查点调节剂或抗体-药物缀合物。其中，7种（曲美木单抗、spartalizumab、BCD-100、omburtamab、mirvetuximab soravtansine、曲妥珠单抗duocarmazine和depatuxizumab mafodotin）正在临床研究中进行评估，主要完成日期为2018年底和2019年，因此是“观察抗体”。我们期待着在本系列文章的下一期中记录这些和其他“值得关注的抗体”所取得的进展。
For the past 10 years, the annual 'Antibodies to watch' articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, we expanded the scope of the data presented to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. Our data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17-25%, depending on the therapeutic area (cancer vs. non-cancer). In 2018, a record number (12) of antibodies (erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), burosumab (Crysvita), lanadelumab (Takhzyro), caplacizumab (Cablivi), mogamulizumab (Poteligeo), moxetumomab pasudodox (Lumoxiti), cemiplimab (Libtayo), ibalizumab (Trogarzo), tildrakizumab (Ilumetri, Ilumya), emapalumab (Gamifant)) that treat a wide variety of diseases were granted a first approval in either the European Union (EU) or United States (US). As of November 2018, 4 antibody therapeutics (sacituzumab govitecan, ravulizumab, risankizumab, romosozumab) were being considered for their first marketing approval in the EU or US, and an additional 3 antibody therapeutics developed by Chinese companies (tislelizumab, sintilimab, camrelizumab) were in regulatory review in China. In addition, our data show that 3 product candidates (leronlimab, brolucizumab, polatuzumab vedotin) may enter regulatory review by the end of 2018, and at least 12 (eptinezumab, teprotumumab, crizanlizumab, satralizumab, tanezumab, isatuximab, spartalizumab, MOR208, oportuzumab monatox, TSR-042, enfortumab vedotin, ublituximab) may enter regulatory review in 2019. Finally, we found that approximately half (18 of 33) of the late-stage pipeline of antibody therapeutics for cancer are immune checkpoint modulators or antibody-drug conjugates. Of these, 7 (tremelimumab, spartalizumab, BCD-100, omburtamab, mirvetuximab soravtansine, trastuzumab duocarmazine, and depatuxizumab mafodotin) are being evaluated in clinical studies with primary completion dates in late 2018 and in 2019, and are thus 'antibodies to watch'. We look forward to documenting progress made with these and other 'antibodies to watch' in the next installment of this article series.