Biosimilars of Monoclonal Antibodies

What Are Biosimilars?

Biologics are critical components in the treatment of patients with cancer. Biosimilars - biologics that are highly similar to approved biologics - offer a potential opportunity to increase access to biologics by stimulating price competition and may lower healthcare costs. The active substance of a biosimi­lar and the original (approved medicine) are essentially the same biological substance, though there may be minor differences due to their complex nature and the production methods.

A consequence of the astronomical commercial value of mAbs associated with the patent expiry date (or estimated expiry date) is their attractiveness as candidates for biosimilar drugs.

An appropriate definition of biosimilars includes the following:

  • Biologic product with primary structure identical to the reference product that has been approved in the concerned jurisdiction;
  • Biosimilarity development pathway involving rele­vant orthogonal analytical comparability methods, and nonclinical and clinical models;
  • Quality, nonclinical and clinical attributes are sufficiently similar, yet not necessarily identical between the biosimilar and the reference product.

Biosimilars are more complex than small-molecule drugs and generics. Biological medicines (Biologics) are large, complex molecules produced from living organisms that are often difficult to characterize and therefore difficult to copy. Generic medicines (Generics) usually consist of small, identical molecules that are chemically synthesized. It is important to understand several key differences between biologics and small-molecule drugs. In addition, the manufacturing process for biologics is more complex than for small-molecule drugs, which requires multiple steps for cloning; selecting, maintaining, and expanding the cell line; and isolating, purifying, and characterizing the product (Fig. 1). Small-molecule drugs are synthesized through a series of predictable chemical reactions that can be reliably reproduced to yield identical copies.

Biosimilars of Monoclonal Antibodies Figure 1. Biologic manufacturing includes multiple steps that may vary between manufacturers, potentially leading to differences between a biosimilar and its reference product that cannot be fully characterized with available analytical methods. In contrast, small-molecule drugs are manufactured through chemical reactions that can be reliably reproduced to make identical copies (generics) that can be fully characterized.

Development of Monoclonal Antibody Biosimilars

Designed to be highly similar to originator biologic products, biosimilars represent an opportunity to increase access and reduce costs for patients and healthcare systems. Biosimilars of monoclonal need to demonstrate similar but not identical quality of nonclinical and clinical attributes. Not all data of the originator product need to be recapitulated, as large numbers of patient-years of exposure data are already available. A well-designed development program establishes biosimilarity based on structural, functional, preclinical, and clinical evaluation. A systematic approach for characterization of structural and functional similarity of a biosimilar molecule to the originator molecule provides specifications to guide the development of biosimilars. Biosimilar endpoints are defined for each tier of characterization, and evaluation of successive tiers addresses additional relevance of biosimilarity. Thus, biosimilar development is largely based on the safety profiles of the originator product. The biosimilarity analysis of biosimilars development is described as a five-step process:

Biosimilars of Monoclonal Antibodies

Unlike the development of novel biologics, biosimilar data focus heavily on the molecular characterization of the mAb with randomised clinical studies confirming that any differences in physico-chemical or biological characterization compared with the reference mAb do not affect efficacy or safety (Figure 2). The challenge of biosimilar development requires intricate reverse engineering, as biologic drugs exhibit great molecular complexity and are sensitive to variations in manufacturing and handling.

Biosimilars of Monoclonal Antibodies Figure 2 Comparability and biosimilarity design of a biosimilar

Common monoclonal antibody biosimilars are listed below, along with the corresponding research-use-only products provided by Creative Biolabs:

List by INNList by targets
ABCD E FGILMNOPRSTUVZ
INN Target Product Name Product CAT Overview
Daclizumab IL2RA Anti-Human CD25 Recombinant Antibody (Daclizumab) TAB-023 Daclizumab Overview
Detumomab B-cell Lymphomas Anti-B Cell Lymphomas Recombinant Antibody (Detumomab) TAB-737 Detumomab Overview
Dusigitumab IGF2 Anti-IGF2 Recombinant Antibody (Dusigitumab) TAB-740 Dusigitumab Overview
INN Target Product Name Product CAT Overview
Narnatumab MST1R Anti-Human RON Recombinant Antibody (Narnatumab) TAB-184
Nebacumab Endotoxin Anti-Endotoxin Recombinant Antibody (Nebacumab) TAB-767 Nebacumab Overview
INN Target Product Name Product CAT Overview
Tadocizumab ITGB3 Anti-Human Integrin lpha 2b beta 3 Recombinant Antibody Fab Fragment (Tadocizumab) TAB-109-F(E)
Talizumab IgE Fc Anti-Human IgE Fc Recombinant Antibody (Talizumab) TAB-886 Talizumab Overview
Tamtuvetmab CD52 Anti-Canine CD52 Recombinant Antibody (Tamtuvetmab) TAB-469CQ
Technetium (99mTc) Nofetumomab Merpentan MS4A1 Anti-MS4A1 Recombinant Antibody (Technetium (99MTC) Nofetumomab Merpentan) TAB-711
Telimomab CD5 Mouse Anti-CD5 Recombinant Antibody (clone Telimomab); Fab Fragment TAB-885 Telimomab Overview
Tenatumomab TNC Anti-Human Tenascin C/TNC Recombinant Antibody (Tenatumomab) TAB-877 Tenatumomab Overview
Ticilimumab CTLA4 Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206 Ticilimumab Overview
Tremelimumab CTLA4 Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206 Tremelimumab Overview
Ticilimumab (= Tremelimumab) CTLA4 Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206 Ticilimumab Overview
Tildrakizumab IL23A Anti-Human IL23 Recombinant Antibody (Tildrakizumab) TAB-875 Tildrakizumab Overview
Timigutuzumab ERBB2 Anti-Human ERBB2 Recombinant Antibody (Timigutuzumab) TAB-468CQ
Timolumab AOC3 Anti-Human AOC3 Recombinant Antibody (Timolumab) TAB-455CQ Timolumab Overview
Toralizumab CD40LG Anti-Human CD40 ligand Recombinant Antibody (Toralizumab) TAB-876 Toralizumab Overview
Tovetumab PDGFRA Anti-Human CD140a Recombinant Antibody (Tovetumab) TAB-878
Tralokinumab IL13 Anti-Human IL13 Recombinant Antibody (Tralokinumab) TAB-218 Tralokinumab Overview
Trastuzumab ERBB2 Anti-Human ErbB2 Recombinant Antibody (Trastuzumab) TAB-005 Trastuzumab Overview
Tregalizumab CD4 Anti-Human CD4 Recombinant Antibody (Tregalizumab) TAB-260 Tregalizumab Overview
Tucotuzumab Celmoleukin EPCAM Humanized Anti-EPCAM Recombinant Antibody (clone Tucotuzumab) TAB-213 Tucotuzumab Celmoleukin Overview
INN Target Product Name Product CAT Overview
Ustekinumab IL12+IL23 Anti-Human IL12+IL23 Recombinant Antibody (Ustekinumab) TAB-063 Ustekinumab Overview
INN Target Product Name Product CAT Overview
Zanolimumab CD4 Anti-Human CD4 Recombinant Antibody (Zanolimumab) TAB-039 Zanolimumab Overview
Zolimomab CD5 Mouse Anti-CD5 Recombinant Antibody (clone Zolimomab) TAB-884 Zolimomab Overview
ABC E FGHILMNPRST
Target INN Product Name Product CAT Overview
B. anthracis PA Raxibacumab Anti-B. Anthracis Anthrax Protective Antigen (Raxibacumab) TAB-224 Raxibacumab Overview
B-cell Lymphomas Detumomab Anti-B Cell Lymphomas Recombinant Antibody (Detumomab) TAB-737 Detumomab Overview
Target INN Product Name Product CAT Overview
C. difficile toxin B Bezlotoxumab Anti-C. Diff Toxin B Recombinant Antibody (Bezlotoxumab) TAB-725 Bezlotoxumab Overview
C5 Pexelizumab Anti-Human C5 Recombinant Antibody (Pexelizumab) TAB-901 Pexelizumab Overview
CA9 Girentuximab Anti-CAIX/CA9 Recombinant Antibody (Girentuximab) TAB-707 Girentuximab Overview
CCL11 Bertilimumab Anti-CCL11 Recombinant Antibody (Bertilimumab) TAB-724 Bertilimumab Overview
CCL2 Carlumab Anti-Human MCP-1 Recombinant Antibody (Carlumab) TAB-117 Carlumab Overview
CCR2 Plozalizumab Anti-Human CCR2 Recombinant Antibody (Plozalizumab) TAB-444CQ Plozalizumab Overview
CD15 Fanolesomab Anti-Human CD15 Recombinant Antibody (Fanolesomab) TAB-H32 Fanolesomab Overview
CD22 Inotuzumab Ozogamicin Humanized Anti-CD22 Recombinant Antibody (clone Inotuzumab) TAB-198 Inotuzumab Ozogamicin Overview
CD22 Pinatuzumab Vedotin Humanized Anti-CD22 Recombinant Antibody (clone Pinatuzumab) TAB-899 Pinatuzumab Vedotin Overview
CD23 Lumiliximab Anti-CD23 Recombinant Antibody Lumiliximab(Lumiliximab) TAB-760
CD248 Ontuxizumab Anti-CD248 Recombinant Antibody (Ontuxizumab) TAB-773 Ontuxizumab Overview
CD33 Gemtuzumab Ozogamicin Anti-Human CD33 Recombinant Antibody (Gemtuzumab Ozogamicin) TAB-H37 Gemtuzumab Ozogamicin Overview
CD37 Lilotomab Anti-Human CD37 Recombinant Antibody (Lilotomab) TAB-467CQ
CD37 Otlertuzumab Anti-Human CD37 Recombinant Antibody (Otlertuzumab) TAB-904 Otlertuzumab Overview
CD3E Ertumaxomab Anti-Human CD3E Recombinant Antibody (Ertumaxomab) TAB-H28 Ertumaxomab Overview
CD3E Visilizumab Anti-CD3E Recombinant Antibody (Visilizumab) TAB-714 Visilizumab Overview
CD4 Clenoliximab Anti-CD4 Recombinant Antibody (Clenoliximab) TAB-732 Clenoliximab Overview
CD4 Tregalizumab Anti-Human CD4 Recombinant Antibody (Tregalizumab) TAB-260 Tregalizumab Overview
CD4 Zanolimumab Anti-Human CD4 Recombinant Antibody (Zanolimumab) TAB-039 Zanolimumab Overview
CD40 Bleselumab Anti-Human CD40 Recombinant Antibody (Bleselumab) TAB-006ML
CD40 Lucatumumab Anti-CD40 Recombinant Antibody (Lucatumumab) TAB-759 Lucatumumab Overview
CD40 Selicrelumab Anti-Human CD40 Recombinant Antibody (Selicrelumab) TAB-470CQ
CD40LG Toralizumab Anti-Human CD40 ligand Recombinant Antibody (Toralizumab) TAB-876 Toralizumab Overview
CD44 Bivatuzumab Anti-CD44 Recombinant Antibody (Bivatuzumab) TAB-727 Bivatuzumab Overview
CD40 Bleselumab Anti-Human CD40 Recombinant Antibody (Bleselumab) TAB-006ML Bleselumab Overview
CD5 Telimomab Mouse Anti-CD5 Recombinant Antibody (clone Telimomab); Fab Fragment TAB-885 Telimomab Overview
CD5 Zolimomab Mouse Anti-CD5 Recombinant Antibody (clone Zolimomab) TAB-884 Zolimomab Overview
CD52 Tamtuvetmab Anti-Canine CD52 Recombinant Antibody (Tamtuvetmab) TAB-469CQ
CD70 Vorsetuzumab Anti-Human CD70 Recombinant Antibody (Vorsetuzumab) TAB-H76 Vorsetuzumab Overview
CD70 Vorsetuzumab Mafodotin Anti-Human CD70 Recombinant Antibody (Vorsetuzumab Mafodotin) TAB-882 Vorsetuzumab Mafodotin Overview
CD80 Galiximab Anti-Human CD80 Recombinant Antibody (Galiximab) TAB-215
CEACAM1 Arcitumomab Anti-Human CEA Recombinant Antibody Fab Fragment (Arcitumomab) TAB-014-F(E) Arcitumomab Overview
CEACAM5 Altumomab Anti-Human CEACAM5 Recombinant Antibody (Altumomab) TAB-703 Altumomab Overview
CFD Lampalizumab Anti-CFD Recombinant Antibody (Lampalizumab) TAB-754 Lampalizumab Overview
CMV Sevirumab Anti-CMV Recombinant Antibody (Sevirumab) TAB-162 Sevirumab Overview
CTAA16.88 Votumumab Anti-CTAA16.88 Recombinant Antibody (Votumumab) TAB-715
CTLA4 Ticilimumab Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206 Ticilimumab Overview
CTLA4 Ticilimumab (= Tremelimumab) Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206
CTLA4 Tremelimumab Anti-Human CTLA4 Recombinant Antibody (Ticilimumab (Tremelimumab)) TAB-206 Tremelimumab Overview
Target INN Product Name Product CAT Overview
E. coli Stx1B Pritoxaximab Anti-Shiga Toxin 1 B Subunit Recombinant Antibody (Pritoxaximab) TAB-896 Pritoxaximab Overview
E. coli Stx2A Setoxaximab Anti-E. Coli Stx2A Recombinant Antibody (Setoxaximab) TAB-H61
EGFR Cetuximab Anti-Human EGFR Recombinant Antibody (Cetuximab) TAB-003 Cetuximab Overview
EGFR Futuximab/Zatuximab Anti-EGFR/HER1 Recombinant Antibody (Futuximab/Zatuximab) TAB-750 Futuximab/Zatuximab Overview
EGFR Imgatuzumab Anti-EGFR Recombinant Antibody (Imgatuzumab) TAB-753 Imgatuzumab Overview
EGFR Matuzumab Anti-Human EGFR Recombinant Antibody (Matuzumab) TAB-165 Matuzumab Overview
EGFR Modotuximab Anti-Human EGFR Recombinant Antibody (Modotuximab) TAB-H49 Modotuximab Overview
Endotoxin Nebacumab Anti-Endotoxin Recombinant Antibody (Nebacumab) TAB-767 Nebacumab Overview
EPCAM Adecatumumab Anti-Human EPCAM Recombinant Antibody (Adecatumumab) TAB-106 Adecatumumab Overview
EPCAM Citatuzumab Bogatox Anti-Human EpCAM Recombinant Antibody Fab Fragment, 17-1A (Citatuzumab Bogatox) TAB-112-F(E) Citatuzumab Bogatox Overview
EpCAM Edrecolomab Anti-Human EpCAM/17-1A Recombinant Antibody (Edrecolomab) TAB-701 Edrecolomab Overview
EPCAM Tucotuzumab Celmoleukin Humanized Anti-EPCAM Recombinant Antibody (clone Tucotuzumab) TAB-213 Tucotuzumab Celmoleukin Overview
ERBB2 Margetuximab Anti-ERBB2 Recombinant Antibody (Margetuximab) TAB-761 Margetuximab Overview
ERBB2 Trastuzumab Anti-Human ErbB2 Recombinant Antibody (Trastuzumab) TAB-005 Trastuzumab Overview
ERBB2 Timigutuzumab Anti-Human ERBB2 Recombinant Antibody (Timigutuzumab TAB-468CQ Timigutuzumab Overview
ERBB3 Seribantumab Anti-Human ERBB3/ErbB 3 Recombinant Antibody (Seribantumab) TAB-892 Seribantumab Overview
Target INN Product Name Product CAT Overview
IAV HA Firivumab Anti-IAV HA Recombinant Antibody (Firivumab) TAB-H33
IFNA1 Faralimomab Anti-IFNA1 Recombinant Antibody (Faralimomab) TAB-747 Faralimomab Overview
IFNA1 Sifalimumab Anti-Human IFNA1 Recombinant Antibody (Sifalimumab) TAB-H62 Sifalimumab Overview
IFNG Fontolizumab Anti-Human IFNG Recombinant Antibody (Fontolizumab) TAB-041 Fontolizumab Overview
IgE Fc Talizumab Anti-Human IgE Fc Recombinant Antibody (Talizumab) TAB-886 Talizumab Overview
IGF1R Cixutumumab Anti-Human IGF1 Receptor Recombinant Antibody (Cixutumumab) TAB-078 Cixutumumab Overview
IGF1R Figitumumab Anti-Human IGF1 Receptor Recombinant Antibody (Figitumumab) TAB-232 Figitumumab Overview
IGF2 Dusigitumab Anti-IGF2 Recombinant Antibody (Dusigitumab) TAB-740 Dusigitumab Overview
IGHE Omalizumab Anti-Human IGHE Recombinant Antibody (Omalizumab) TAB-007 Omalizumab Overview
IL12+IL23 Briakinumab Anti-Human IL12+IL23 Recombinant Antibody (Briakinumab) TAB-103 Briakinumab Overview
IL12+IL23 Ustekinumab Anti-Human IL12+IL23 Recombinant Antibody (Ustekinumab) TAB-063 Ustekinumab Overview
IL13 Anrukinzumab Anti-Human IL13 Recombinant Antibody (Anrukinzumab) TAB-H05 Anrukinzumab Overview
IL13 Tralokinumab Anti-Human IL13 Recombinant Antibody (Tralokinumab) TAB-218 Tralokinumab Overview
IL17A Perakizumab Anti-Human IL17A Recombinant Antibody (Perakizumab) TAB-H57 Perakizumab Overview
IL17RA Brodalumab Human Anti-IL17RA Recombinant Antibody (TAB-134) TAB-134 Brodalumab Overview
IL1B Canakinumab Anti-Human IL1Beta Recombinant Antibody (Canakinumab) TAB-021 Canakinumab Overview
IL20 Fletikumab Anti-Human IL20 Recombinant Antibody (Fletikumab) TAB-H34 Fletikumab Overview
IL23A Brazikumab Anti-Human IL23A Recombinant Antibody (Brazikumab) TAB-008ML Brazikumab Overview
IL23A Tildrakizumab Anti-Human IL23 Recombinant Antibody (Tildrakizumab) TAB-875 Tildrakizumab Overview
IL2RA Basiliximab Anti-Human CD25 Recombinant Antibody (Basiliximab) TAB-004 Basiliximab Overview
IL2RA Daclizumab Anti-Human CD25 Recombinant Antibody (Daclizumab) TAB-023 Daclizumab Overview
IL6 Olokizumab Anti-Human IL-6 Recombinant Antibody (Olokizumab) TAB-253 Olokizumab Overview
IL6 Sirukumab Anti-Human IL6 Recombinant Antibody (Sirukumab) TAB-097 Sirukumab Overview
ITGA2 Vatelizumab Anti-Human ITGA2 Recombinant Antibody (Vatelizumab) TAB-251 Vatelizumab Overview
ITGA2B Abciximab Anti-Human CD41 Recombinant Antibody Fab Fragment (Abciximab) TAB-015-F(E) Abciximab Overview
ITGA4 Etrolizumab Anti-Human Integrin alpha 4 beta 7 Recombinant Antibody (Etrolizumab) TAB-135 Etrolizumab Overview
ITGA5 Volociximab Anti-Human Integrin alpha 5 beta 1 Recombinant Antibody (Volociximab) TAB-077
ITGAV Abituzumab Anti-Human ITGAV Recombinant Antibody (Abituzumab) TAB-H01 Abituzumab Overview
ITGB3 Tadocizumab Anti-Human Integrin lpha 2b beta 3 Recombinant Antibody Fab Fragment (Tadocizumab) TAB-109-F(E)
Target INN Product Name Product CAT Overview
LOXL2 Simtuzumab Anti-Human LOXL2 Recombinant Antibody (Simtuzumab) TAB-890 Simtuzumab Overview
Target INN Product Name Product CAT Overview
RSPO3 Rosmantuzumab Anti-Human RSPO3 Recombinant Antibody (Rosmantuzumab) TAB-449CQ Rosmantuzumab Overview

Future Outlook

The development of biosimilars for complex mAbs, which are the highest-selling biologics and is a key therapeutic class for diseases including various cancers and autoimmune disorders such as rheumatoid arthritis, is accelerating rapidly owing to the upcoming patent expiry of top-selling drugs. Despite technical and manufacturing hurdles, these complexand large molecules especially antibody-based proteins are poised to be the leaders of the new wave of biosimilars that are likely to receive approval in the coming years. Driven by the prospect of patent expirations of blockbuster mAbs in the next few years (Table 1), many pharmaceutical companies have entered the rapidly growing mAb biosimilars market.

Table 1 Selected key products for which monoclonal antibody biosimilars are in development

Biosimilars of Monoclonal Antibodies *The date given is based on the expected expiry of patents protecting the original molecule.

Biosimilars are a huge opportunity. The market will eventually become a huge business no matter how slowly it starts. There are several elements to boost biosimilars’ market growth including patent expiries, defined regulatory pathways and escalating healthcare costs. According to some professional investigational agency, it is estimated that biologic drugs worth $70-$80 billion will lose exclusivity in the next 5 years globally. Moreover, the launch of innovation production platforms will reduce the cost of biosimilars production, thus providing substantial price differentiation. In the next 4 to 5 years, two-thirds of the patents will expire in biosimilars and specialty segments, such as high profit margins of biomedical fields.

To boost your biosimilar research programs, Creative Biolabs provides a full range of therapeutic antibodies currently available for research of a wide variety of diseases. We have rich experience for over 10 years to offer high quality antibodies that will meet your any requirement.

References

  1. Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19:412.
  2. Natasha Udpa and Ryan P. Million.Monoclonal antibody biosimilars. Nature Reviews Drug Discovery, Published online 18 Dec 2015.

For research use only. Not intended for any clinical use.

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