The introduction of biosimilars of biological agents for which the patents and exclusivity periods have expired is an attractive way of reducing healthcare spending through price competition with the reference product. In oncology, biosimilars of growth factors for supportive therapy were the pioneers; now, monoclonal antibody biosimilars are conquering the market. In Europe, this is currently limited to biosimilars of the monoclonal antibodies trastuzumab and rituximab. However, the pipeline is full and several monoclonal antibody biosimilars in oncology are now in late-stage development. We are expecting not only more biosimilar versions of the top 3 blockbuster monoclonal antibodies, trastuzumab, rituximab and bevacizumab, to enter the market; as patent expiration of multiple other cancer biologicals will occur in the next few years, the biosimilar landscape will become much more diversified. Several biosimilars of monoclonal antibodies used in targeted therapy such as cetuximab, pertuzumab, or denosumab are in early development.

Keywords:
Biosimilar, Trastuzumab, Rituximab, Bevacizumab, Cetuximab
1.
Weiner GJ: Building better monoclonal antibody-based therapeutics. Nat Rev Cancer 2015;15:361-370.
2.
GaBI Journal Editor: Patent expiry dates for biologicals: 2017 update. GaBI J 2018;7:29-34.
3.
Ekman N, Vulto AG, Cornes P: Reducing healthcare costs and building trust in biosimilar medicines. GaBI J 2016;5:84-88.
4.
Mullard A: 2015 FDA drug approvals. Nat Rev Drug Discov 2016;15:73-77.
5.
European Medicines Agency (EMA): Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products, 2014. www.ema.europa.eu/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf.
6.
Weise M, Bielsky MC, De Smet K, Ehmann F, Ekman N, Giezen TJ, Gravanis I, Heim HK, Heinonen E, Ho K, Moreau A, Narayanan G, Kruse NA, Reichmann G, Thorpe R, van Aerts L, Vleminckx C, Wadhwa M, Schneider CK: Biosimilars: what clinicians should know. Blood 2012;120:5111-5117.
7.
Tebbey PW, Varga A, Naill M, Clewell J, Venema J: Consistency of quality attributes for the glycosylated monoclonal antibody Humira® (adalimumab). MAbs 2015;7:805-811.
8.
Schiestl M, Stangler T, Torella C, Cepeljnik T, Toll H, Grau R: Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat Biotechnol 2011;29:310-312.
9.
Kim S, Song J, Park S, Ham S, Paek K, Kang M, Chae Y, Seo H, Kim HC, Flores M: Drifts in ADCC-related quality attributes of Herceptin®: impact on development of a trastuzumab biosimilar. MAbs 2017;9:704-714.
10.
IMS Institute for Health Informatics: Delivering on the potential of biosimilar medicines. Parsippany, NJ, IMS Institute for Health Informatics, 2016. www.medicinesforeurope.com/wp-content/uploads/2016/03/IMS-Institute-Biosimilar-Report-March-2016-FINAL.pdf.
11.
IQVIA: Advancing biosimilar sustainability in Europe. A multi-stakeholder assessment. IQVIA, Durham, NC, 2018. www.iqvia.com/institute/reports/advancing-biosimilar-sustainability-in-europe.
12.
Aapro M, Cornes P, Abraham I: Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. J Oncol Pharm Pract 2012;18:171-179.
13.
Gascon P, Tesch H, Verpoort K, Rosati MS, Salesi N, Agrawal S, Wilking N, Barker H, Muenzberg M, Turner M: Clinical experience with Zarzio® in Europe: what have we learned? Support Care Cancer 2013;21:2925-2932.
14.
Aapro M, Krendyukov A, Schiestl M, Gascon P: Epoetin biosimilars in the treatment of chemotherapy-induced anemia: 10 years' experience gained. BioDrugs 2018;32:129-135.
15.
Derbyshire M: Patent expiry dates for best-selling biologicals: 2017 update. GaBI J 2018;7:29-34.
16.
Agostini C, Canonica GW, Maggi E: European Medicines Agency guideline for biological medicinal products: a further step for a safe use of biosimilars. Clin Mol Allergy 2015;13:3.
17.
European Medicines Agency: Applications for new human medicines under evaluation by the Committee for Medicinal Products for Human Use, 2019. www.ema.europa.eu/documents/report/applications-new-human-medicines-under-evaluation-chmp-january-2019_en.pdf.
18.
European Medicines Agency: Mabthera, INN-rituximab.
19.
Kim WS, Buske C, Ogura M, Jurczak W, Sancho JM, Zhavrid E, Kim JS, Hernandez-Rivas JA, Prokharau A, Vasilica M, Nagarkar R, Osmanov D, Kwak LW, Lee SJ, Lee SY, Bae YJ, Coiffier B: Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol 2017;4:e362-e373.
20.
European Medicines Agency: Truxima, INN-rituximab.
21.
Jurczak W, Ilidia M, Govindbabu KS, Eduardo M, Ascuncion EM, Giri P, Nelson C, Juliana P, Luiza A, Sergey A, Dzhelil O, Pultar P, Cherfi A, Zhu P, Amersdorffer J: A phase III efficacy and safety study of the proposed rituximab biosimilar GP2013 versus rituximab in patients with previously untreated advanced follicular lymphoma. Blood 2016;128:1809.
22.
European Medicines Agency: Avastin, INN-bevacizumab.
23.
U.S. FDA: FDA approves first biosimilar for the treatment of cancer. Media release, 2017. www.fda.gov/newsevents/newsroom/pressannouncements/ucm576112.htm.
24.
Casak SJ, Lemery SJ, Chung J, Fuchs C, Schrieber SJ, Chow ECY, Yuan W, Rodriguez L, Gwise T, Rowzee A, Lim S, Keegan P, McKee AE, Pazdur R: FDA's approval of the first biosimilar to bevacizumab. Clin Cancer Res 2018;24:4365-4370.
25.
Filon O, Orlov S, Burdaeva O, Kopp MV, Kotiv B, Alekseev S, Pecheniy A, Stroyakovskiy D, Gladkov O, Khorinko A, Matrosova M, Galiulin R, Skopin P, Mukhametsina G, Odarchenko S, Kulik S, Kulyaba J, Adamchuk G, Vinnyk Y, Tjulandin S: Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC. J Clin Oncol 2015;33:8057.
26.
Peraza MA, Rule KE, Shiue MHI, Finch GL, Thibault S, Brown PR, Clarke DW, Leach MW: Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab. Regul Toxicol Pharmacol 2018;95:236-243.
27.
Biosimilar Development: Anti-VEGF and anti-VEGF-R biosimilars and biosuperiors of Avastin, Cyramza, Eylea and Lucentis - 2017; new report launched. www.biosimilardevelopment.com/doc/anti-vegf-and-anti-vegf-r-biosimilars-and-biosuperiors-of-avastin-cyramza-eylea-and-lucentis-new-report-launched-0001.
28.
European Medicines Agency: Herceptin, INN-trastuzumab.
29.
GaBI Online: Generics and Biosimilars Initiative. Biosimilars approved in Europe 2011. www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe.
30.
European Medicines Agency: Erbitux, INN-cetuximab.
31.
Derbyshire M: Patent expiry dates for biologicals: 2016 update. GaBI J 2017;6:27-30.
32.
DiGrande S: Cetuximab biosimilars are on the horizon. Center for Biosimilars, 2018. www.centerforbiosimilars.com/news/cetuximab-biosimilars-are-on-the-horizon.
33.
News provided by Sorrent Therapeutics, Inc., San Diego, CA: Sorrento announces positive data from phase 3 studies of biosimilar antibodies, STI-001 and STI-002. www.prnewswire.com/news-releases/sorrento-announces-positive-data-from-phase-3-studies-of-biosimilar-antibodies-sti-001-and-sti-002-300202054.html.
34.
European Medicines Agency: Vectibix, INN-panitumumab.
35.
Taniguchi H, Yamanaka T, Sakai D, Yamazaki K, Muro K, Peeters M: Panitumumab versus cetuximab in patients with wild-type KRAS exon 2 metastatic colorectal cancer who received prior bevacizumab therapy: a combined analysis of individual patient data from ASPECCT and WJOG6510G. J Clin Oncol 2018;36:745.
36.
The Center for Biosimilars: Assessing the Next Wave of Biosimilars. June 18, 2018. www.centerforbiosimilars.com/contributor/zs/2018/06.
37.
Wong DJ, Hurvitz SA: Recent advances in the development of anti-HER2 antibodies and antibody-drug conjugates. Ann Transl Med 2014;2:122.
38.
European Medicines Agency: Kadcyla, INN-trastuzumab emtansine.
39.
European Medicines Agency: Perjeta, INN-pertuzumab.
40.
European Medicines Agency: Xgeva, INN-denosumab.
41.
Collin M: Immune checkpoint inhibitors: the battle of giants. Pharm Pat Anal 2017;6:135-137.
42.
Mullard A: Top product sales forecasts for 2018. Nat Rev Drug Discov 2018;17:86.
43.
Mullard A: 2017 FDA drug approvals. The FDA approved 46 new drugs last year, the highest total in more than two decades. Nat Rev Drug Discov 2018;17:81-85.
44.
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators: Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018;379:2108-2121.
45.
Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskii D, Pikiel J, Eniu A, Komov D, Morar-Bolba G, Li RK, Rusyn A, Lee SJ, Lee SY, Esteva FJ: CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol 2017;18:917-928.
46.
Von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V: Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol 2018;19:987-998.
47.
Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Shparyk Y, Moiseyenko V, Bello M 3rd, Semiglazov V, Lee Y, Lim J: A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: final safety, immunogenicity and survival results. Eur J Cancer 2018;93:19-27.
48.
Pegram M, Tan-Chiu E, Freyman A, Vana A, Hilton F, Zacharchuk C, Ewesuedo R: A randomized, double-blind study of PF-05280014 (a potential trastuzumab biosimilar) vs. trastuzumab, both in combination with paclitaxel, as first-line treatment for HER2-positive metastatic breast cancer. Ann Oncol 2017;28:mdx365.001a.
49.
Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I: Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer 2018;119:266-273.
50.
Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators: Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)-positive metastatic breast cancer: a randomized clinical trial. JAMA 2017;317:37-47.
51.
Casak SJ, Lemery SJ, Chung J, Fuchs C, Schrieber SJ, Chow ECY, Yuan WS, Rodriguez L, Gwise T, Rowzee A, Lim S, Keegan P, McKee AE, Pazdur R: FDA's approval of the first biosimilar to bevacizumab. Clin Cancer Res 2018;24:4365-4370.
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2019
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