Challenges and opportunities for the future of monoclonal antibody development: Improving safety assessment and reducing animal use

References

• Mullard A. 2015 FDA drug approvals. Nat Rev Drug Discov 2016; 15(2):73–6; PMID:26837582; https://doi.org/10.1038/nrd.2016.15
   PubMed Web of Science ®Google Scholar
• EMA. European public assessment reports, human medicines [Internet]. The European Medicines Agency [cited 2016 October 19]. 2016 Available from: http://www.ema.europa.eu/ema/index.jsp?curl = pages%2Fmedicines%2Flanding%2Fepar_search.jsp&mid=&searchTab = searchByAuthType&alreadyLoaded = true&isNewQuery = true&status = Authorised&keyword = Enter+keywords&searchType = name&taxonomyPath=&treeNumber=&searchGenericType = biosimilars&genericsKeywordSearch=Submit.
   Google Scholar
• FDA. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm 2016.
   Google Scholar
• EMA. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/06/WC500144941.pdf. 2013.
   Google Scholar
• FDA. U.S. Food and Drug Administration Press Release. 6 March 2015: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm. 2015.
   Google Scholar
• FDA. U.S. Food and Drug Administration Press Release. 5 April 2016: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm494227.htm. 2016.
   Google Scholar
• Buckley LA, Chapman K, Burns-Naas LA, Todd MD, Martin PL, Lansita JA. Considerations regarding nonhuman primate use in safety assessment of biopharmaceuticals. Int J Toxicol 2011; 30(5):583-90; PMID:22013138; https://doi.org/10.1177/1091581811415875
   PubMed Web of Science ®Google Scholar
• Bussiere JL. Species selection considerations for preclinical toxicology studies for biotherapeutics. Expert Opin Drug Metab Toxicol 2008; 4(7):871-7; PMID:18624676; https://doi.org/10.1517/17425255.4.7.871
   PubMed Web of Science ®Google Scholar
• Chapman K, Pullen N, Coney L, Dempster M, Andrews L, Bajramovic J, Baldrick P, Buckley L, Jacobs A, Hale G, et al. Preclinical development of monoclonal antibodies: Considerations for the use of non-human primates. MAbs 2009; 1(5):505-16; PMID:20065651; https://doi.org/10.4161/mabs.1.5.9676
   PubMed Web of Science ®Google Scholar
• Chapman K, Pullen N, Graham M, Ragan I. Preclinical safety testing of monoclonal antibodies: The significance of species relevance. Nat Rev Drug Discov 2007; 6(2):120-6; PMID:17268483; https://doi.org/10.1038/nrd2242
   PubMed Web of Science ®Google Scholar
• Chapman KL, Andrews L, Bajramovic JJ, Baldrick P, Black LE, Bowman CJ, Buckley LA, Coney LA, Couch J, Maggie Dempster A, et al. The design of chronic toxicology studies of monoclonal antibodies: Implications for the reduction in use of non-human primates. Regul Toxicol Pharmacol 2012; 62(2):347-54; PMID:22100994; https://doi.org/10.1016/j.yrtph.2011.10.016
   PubMed Web of Science ®Google Scholar
• Brennan FR, Cavagnaro J, McKeever K, Schutten M, Vahle J, Weinbauer G, Black L. Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on risk assessment for humans. Ready for submission. 2017.
   Google Scholar
• Judson R, Kavlock R, Martin M, Reif D, Houck K, Knudsen T, Richard A, Tice RR, Whelan M, Xia M, et al. Perspectives on validation of high-throughput assays supporting 21st century toxicity testing. ALTEX 2013; 30(1):51-6; PMID:23338806; https://doi.org/10.14573/altex.2013.1.051
   PubMedGoogle Scholar
• https://aopwiki.org.
   Google Scholar
• NIH. http://www.nih.gov/news-events/news-releases/nih-darpa-fda-collaborate-develop-cutting-edge-technologies-predict-drug-safety. 2011.
   Google Scholar
• Emulate. https://emulatebio.com/press/fda-collab-agreement-emulate/. 2017.
   Google Scholar
• van Meer PJ, Kooijman M, Brinks V, Gispen-de Wied CC, Silva-Lima B, Moors EH, Schellekens H. Immunogenicity of mAbs in non-human primates during nonclinical safety assessment. MAbs 2013; 5(5):810-6; PMID:23924803; https://doi.org/10.4161/mabs.25234
   PubMed Web of Science ®Google Scholar
• van Meer PJ, Kooijman M, van der Laan JW, Moors EH, Schellekens H. The value of non-human primates in the development of monoclonal antibodies. Nat Biotechnol 2013; 31(10):882-3; PMID:24104750; https://doi.org/10.1038/nbt.2709
   PubMed Web of Science ®Google Scholar
• DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. J Health Econ 2016; 47:20-33; PMID:26928437; https://doi.org/10.1016/j.jhealeco.2016.01.012
   PubMed Web of Science ®Google Scholar
• Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 2012; 11(3):191-200; PMID:22378269; https://doi.org/10.1038/nrd3681
   PubMed Web of Science ®Google Scholar
• Schulze U, Baedeker M, Chen YT, Greber D. R&D productivity: On the comeback trail. Nat Rev Drug Discov 2014; 13(5):331-2; PMID:24751818; https://doi.org/10.1038/nrd4320
   PubMed Web of Science ®Google Scholar
• Kizhedath A, Wilkinson S, Glassey J. Glassey, applicability of predictive toxicology methods for monoclonal antibody therapeutics: Status Quo and scope. Arch Toxicol 2017; 91(4):1595-612; PMID:27766364; https://doi.org/10.1007/s00204-016-1876-7
   PubMed Web of Science ®Google Scholar
• http://www.vaxdesign.com/mimic-technology.
   Google Scholar
• http://www.stemina.com.
   Google Scholar
• Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol 2014; 32(8):760-72; PMID:25093883; https://doi.org/10.1038/nbt.2989
   PubMed Web of Science ®Google Scholar
• Borenstein JT. Organs-on-Chips: How microsystems technology can transform the drug development process. IEEE Pulse 2016; 7(2):22-6; PMID:26978847; https://doi.org/10.1109/MPUL.2015.2513722
   PubMed Web of Science ®Google Scholar
• Jones HM, Chen Y, Gibson C, Heimbach T, Parrott N, Peters SA, Snoeys J, Upreti VV, Zheng M, Hall SD. Physiologically based pharmacokinetic modeling in drug discovery and development: A pharmaceutical industry perspective. Clin Pharmacol Ther 2015; 97(3):247-62; PMID:25670209; https://doi.org/10.1002/cpt.37
   PubMed Web of Science ®Google Scholar
• Pelkonen O, Turpeinen M, Raunio H. in vivo-in vitro-in silico pharmacokinetic modelling in drug development: Current status and future directions. Clin Pharmacokinet 2011; 50(8):483-91; PMID:21740072; https://doi.org/10.2165/11592400-000000000-00000
   PubMed Web of Science ®Google Scholar
• Valerio LG Jr. In silico toxicology for the pharmaceutical sciences. Toxicol Appl Pharmacol 2009; 241(3):356-70; PMID:19716836; https://doi.org/10.1016/j.taap.2009.08.022
   PubMed Web of Science ®Google Scholar
• Joubert MK, Deshpande M, Yang J, Reynolds H, Bryson C, Fogg M, Baker MP, Herskovitz J, Goletz TJ, Zhou L, et al. Use of in vitro assays to assess immunogenicity risk of antibody-based biotherapeutics. PLoS One 2016; 11(8):e0159328; PMID:27494246; https://doi.org/10.1371/journal.pone.0159328
   PubMed Web of Science ®Google Scholar
• Joubert MK, Hokom M, Eakin C, Zhou L, Deshpande M, Baker M, Goletz T, Kerwin B, Chirmule N, Narhi L, et al. Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses. J Biol Chem 2012 Jul 20; 287(30):25266-79; PMID:22584577; https://doi.org/10.1074/jbc.M111.330902
   PubMed Web of Science ®Google Scholar
• McCulloch DR, Le Goff C, Bhatt S, Dixon LJ, Sandy JD, Apte SS. Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues. Gene Expr Patterns 2009; 9(5):314-23; PMID:19250981; https://doi.org/10.1016/j.gep.2009.02.006
   PubMed Web of Science ®Google Scholar
• Dupuis LE, McCulloch DR, McGarity JD, Bahan A, Wessels A, Weber D, Diminich AM, Nelson CM, Apte SS, Kern CB. Altered versican cleavage in ADAMTS5 deficient mice; a novel etiology of myxomatous valve disease. Dev Biol 2011; 357(1):152-64; PMID:21749862; https://doi.org/10.1016/j.ydbio.2011.06.041
   PubMed Web of Science ®Google Scholar
• Phng LK, Gerhardt H. Angiogenesis: A team effort coordinated by notch. Dev Cell 2009; 16(2):196-208; PMID:19217422; https://doi.org/10.1016/j.devcel.2009.01.015
   PubMed Web of Science ®Google Scholar
• Liu Z, Turkoz A, Jackson EN, Corbo JC, Engelbach JA, Garbow JR, Piwnica-Worms DR, Kopan R. Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice. J Clin Invest 2011; 121(2):800-8; PMID:21266774; https://doi.org/10.1172/JCI43114
   PubMed Web of Science ®Google Scholar
• Hoey T, Yen WC, Axelrod F, Basi J, Donigian L, Dylla S, Fitch-Bruhns M, Lazetic S, Park IK, Sato A, et al. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell 2009; 5(2):168-77; PMID:19664991; https://doi.org/10.1016/j.stem.2009.05.019
   PubMed Web of Science ®Google Scholar
• Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, Lin HC, Yancopoulos GD, Thurston G. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 2006; 444(7122):1032-7; PMID:17183313; https://doi.org/10.1038/nature05355
   PubMed Web of Science ®Google Scholar
• Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006; 444(7122):1083-7; PMID:17183323; https://doi.org/10.1038/nature05313
   PubMed Web of Science ®Google Scholar
• Scehnet JS, Jiang W, Kumar SR, Krasnoperov V, Trindade A, Benedito R, Djokovic D, Borges C, Ley EJ, Duarte A, et al. Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion. Blood 2007; 109(11):4753-60; PMID:17311993; https://doi.org/10.1182/blood-2006-12-063933
   PubMed Web of Science ®Google Scholar
• Couch JA, Zhang G, Beyer JC, de Zafra CL, Gupta P, Kamath AV, Lewin-Koh N, Tarrant J, Allamneni KP, Cain G, et al. Balancing efficacy and safety of an anti-DLL4 antibody through pharmacokinetic modulation. Clin Cancer Res 2016; 22(6):1469-79; PMID:26589434; https://doi.org/10.1158/1078-0432.CCR-15-1380
   PubMed Web of Science ®Google Scholar
• ICH. Preclincal safety evaluation of biotechnology-derived pharmaceuticals. International Conference on Harmonisation (ICH). Topic S6(R1). June 2011; S6(R1).
   Google Scholar
• Sistare FD, Mattes WB, LeCluyse EL. The promise of new technologies to reduce, refine, or replace animal use while reducing risks of drug induced liver injury in pharmaceutical development. ILAR J6 2016; 57(2):186-211; PMID:28053072; https://doi.org/10.1093/ilar/ilw025
   PubMed Web of Science ®Google Scholar
• Barghorn S. Off target toxicity of an anti-amyloid beta antibody for Alzheimer's disease immunotherapy. Presented at IBC's Antibody Engineering & Therapeutics conference December 2013.
   Google Scholar
• Vugmeyster Y, Szklut P, Wensel D, Ross J, Xu X, Awwad M, Gill D, Tchistiakov L, Warner G. Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species. Pharm Res 2011; 28:1696-706. 45; PMID:21424161; https://doi.org/10.1007/s11095-011-0405-x
   PubMed Web of Science ®Google Scholar
• ICH. Final concept paper S11: Nonclinical safety testing in support of development of pediatric medicines. International Council on Harmonisation (ICH). Topic S11. September 2014. Endorsed by the ICH Steering Committee on 10 November 2014., S11.
   Google Scholar
• Clarke J, Hurst C, Martin P, Vahle J, Ponce R, Mounho B, Heidel S, Andrews L, Reynolds T, Cavagnaro J. Duration of chronic toxicity studies for biotechnology-derived pharmaceuticals: Is 6 months still appropriate? Regul Toxicol Pharmacol 2008; 50(1):2-22; PMID:17998153; https://doi.org/10.1016/j.yrtph.2007.08.001
   PubMed Web of Science ®Google Scholar
• ICH. Nonclinical evaluation for anticancer pharmaceuticals. International Conference on Harmonisation (ICH). Topic S9. March 2010; S9.
   Google Scholar