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. 2019 Feb/Mar;11(2):219-238.
doi: 10.1080/19420862.2018.1556465. Epub 2018 Dec 22.

Antibodies to watch in 2019

Affiliations

Antibodies to watch in 2019

Hélène Kaplon et al. MAbs. 2019 Feb/Mar.

Abstract

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.

Keywords: European Medicines Agency; Food and Drug Administration; antibody therapeutics; cancer; immune-mediated disorders; success rates.

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Figures

Figure 1.
Figure 1.
Number of antibody therapeutics entering first-in-human studies per year, 2005–2017. Green bars, all antibody therapeutics. Blue bars, antibody therapeutics for non-cancer indications only. Red bars, antibody therapeutics for cancer only. Dotted lines, 2-year moving averages. Totals include only antibody therapeutics sponsored by commercial firms; those sponsored solely by government, academic or non-profit organizations were excluded. Biosimilar antibodies and Fc fusion proteins were also excluded.
Figure 2.
Figure 2.
Clinical phase transition and approval success rates for antibody therapeutics that entered clinical study during 2000–2009. Green bars, all antibody therapeutics. Blue bars, antibody therapeutics for non-cancer indications only. Red bars, antibody therapeutics for cancer only. Cohorts included only antibody therapeutics sponsored by commercial firms; those sponsored solely by government, academic or non-profit organizations were excluded. Number of molecules that entered clinical study during 2000–09: all, n = 357; non-cancer only, n = 181; cancer only, n = 176. Final fates (approval or termination) are known for 76%. MAbs that had advanced to Phase 1/2 were classified as Phase 2; mAbs that had advanced to Phase 2/3 were classified as Phase 3. Two mAbs with first approvals outside the US/EU regions (italizumab (Alzumab) and Rabishield approvals in India) were classified as Phase 3. Phase transition percentages were calculated as follows: the number of antibody therapeutics that completed a given phase and transitioned to the next was divided by the arithmetic difference between the number that entered the phase and the number that remained in the phase at the time of the calculation. Phase transitions occurring between clinical studies conducted world-wide were included. Approval success were defined as a first US or EU approval; supplemental approvals were not included. Abbreviation RR, regulatory review.
Figure 3.
Figure 3.
Clinical phase transition and approval success rates for antibody therapeutics that entered clinical study during 2005–2014. Green bars, all antibody therapeutics. Blue bars, antibody therapeutics for non-cancer indications only. Red bars, antibody therapeutics for cancer only. Cohorts included only antibody therapeutics sponsored by commercial firms; those sponsored solely by government, academic or non-profit organizations were excluded. Number of molecules that entered clinical study during 2005–14: all, n = 569; non-cancer only, n = 295; cancer only, n = 274. Final fates (approval or termination) are known for 58%. MAbs that had advanced to Phase 1/2 were classified as Phase 2; mAbs that had advanced to Phase 2/3 were classified as Phase 3. Two mAbs with first approvals outside the US/EU regions (italizumab (Alzumab) and Rabishield approvals in India) were classified as Phase 3. Phase transition percentages were calculated as follows: the number of antibody therapeutics that completed a given phase and transitioned to the next was divided by the arithmetic difference between the number that entered the phase and the number that remained in the phase at the time of the calculation. Transitions occurring between clinical studies conducted world-wide were included. Approval success were defined as a first US or EU approval; supplemental approvals were not included. Abbreviation RR, regulatory review.
Figure 4.
Figure 4.
Clinical phases for antibody therapeutics in development. Data as of November 2018. Totals include only antibody therapeutics sponsored by commercial firms; those sponsored solely by government, academic or non-profit organizations were excluded; biosimilars and Fc fusion proteins were excluded. Phase 1/2 included with Phase 2; late-stage studies include pivotal Phase 2, Phase 2/3 and Phase 3. Tables of mAbs in late-stage studies are available at www.antibodysociety.org.
Figure 5.
Figure 5.
Antibodies to watch in 2010–2019. Data from ‘Antibodies to watch’ articles published in mAbs. 2019 data as of November 2018. Totals include only antibody therapeutics sponsored by commercial firms; those sponsored solely by government, academic or non-profit organizations were excluded. Tables of mAbs in late-stage studies are available at www.antibodysociety.org.

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