Stephanie Prezioso, Ph.D. (she/her)

Just a few decades ago, small molecules dominated the drug market, but advances in molecular biology that allow us to better manipulate biological molecules have allowed for a new player to enter the space: Biologics.

Biologics are predicted to occupy a whopping 30% of the therapeutic drug market by 2022 (EvaluatePharma). Even the current top-selling drug, Humira, is an antibody-based biologic, and is predicted to maintain this dominance through 2024. Of the top 50 drugs expected to be the top-sellers by 2024, 21 are fully human or humanized monoclonal antibodies.

This article reviews the 7 monoclonal antibodies that are expected to be the best-selling antibody-based drugs in 2024 according to the 2018 report by market research and consulting firm, EvaluatePharma.

During drug development, commercially available research antibodies are used extensively in the preclinical drug discovery process, especially in target identification and validation studies. Therefore, for each drug, we've also indicated whether it's available for research purposes, and listed the the most widely used research antibodies that bind to the same protein targets, according to data collected by BenchSci.

These 7 drugs can be generally split into two categories: Inflammation modulators and cancer therapies.

Inflammation Modulators

Proinflammatory cytokines are secreted to induce inflammation and are under delicate control in the body. Excessive levels of inflammatory cytokines are often associated with autoimmune diseases such as rheumatoid arthritis, atopic dermatitis (eczema), and Crohn's disease.

These three monoclonal antibodies regulate the activity of proinflammatory cytokines to reduce inflammation.

Humira

Generic name: Adalimumab (fully humanized monoclonal antibody)

Company: AbbVie and Eisai

Protein target: TNFα

Indications: Rheumatoid arthritis, psoriatic arthritis (PsA), ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis (PsO), hidradenitis suppurativa, and juvenile idiopathic arthritis

Mechanism of action: The cytokine TNFα binds to TNFα receptors to induce the inflammatory response in a variety of autoimmune diseases. Adalimumab binds to TNFα to inhibit this interaction and ultimately reduce inflammation. Considering TNFα signalling has been implicated in a variety of inflammatory diseases, Humira has a wide variety of indications, which is related to its huge success.

Adalimumab is available for research purposes under the clone ID: D2E7

Need an antibody to study TNFα (human)?

Dupixent

Generic name: Dupilumab (fully human monoclonal antibody)

Company: Sanofi

Protein target: IL-4Rα

Indications: Atopic dermatitis (eczema) and asthma

Mechanism of action: Binding of the IL-4 and IL-13 cytokines to the IL-4 receptor alpha subunit (IL-4Rα) plays an important role in the inflammatory response associated with allergy, including asthma and eczema. Dupilumab binds to IL-4Rα to block IL-4 and IL-13 signalling and reduce inflammation.

Need an antibody to study IL-4Rα (human)?

Stelara

Generic name: Ustekinumab (fully human monoclonal antibody)

Company: Johnson and Johnson

Protein targets: IL-12 and IL-23

Indications: Psoriasis (PsO), psoriatic arthritis (PsA), Crohn's disease

Mechanism of action: Multiple studies have reported dysregulation of either IL-12 or IL-23 in human immune-mediated diseases such as psoriasis and Crohn's disease. Ustekinumab binds to the p40 domain that's shared by both IL-12 and IL-23. This suppresses their activity by impairing binding to their receptors and reducing the inflammatory response.

Need an antibody to study IL-23 (human)?

Cancer Therapies

Cancer cells have differential gene expression compared to healthy cells, and have multiple mechanisms to evade the immune response.

The following 4 antibodies work by either targeting tumor associated antigens, or by enhancing the immune response to eliminate cancer cells.

Darzalex

Generic name: Daratumumab (fully human monoclonal antibody)

Company: Johnson and Johnson

Protein target: CD38

Indication: Multiple myeloma

Mechanism of action: CD38 is a transmembrane glycoprotein found on the surface of many immune cells. CD38 is involved in receptor-mediated adhesion and signalling in healthy cells, but is overexpressed in multiple myeloma cells. Daratumumab binds to CD38 to inhibit the growth of multiple myeloma cells through a variety of mechanisms including antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxiccity, antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis.

Need an antibody to study CD38 (human)?

Opdivo

Generic name: Nivolumab (fully human monoclonal antibody)

Company: Bristol-Myers Squibb and Ono Pharmaceutical

Protein target: PD-1

Indications: Non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC, kidney cancer), hepatocellular carcinoma, urothelial carcinoma (bladder cancer), squamous cell carcinoma of the head and neck (SCCHN), and Hodgkin lymphoma (cHL)

Mechanism of action: The Programmed Death-1 (PD-1) pathway down-regulates T-cell activation and is critical for preventing autoimmunity. However, this pathway is also involved in anti-tumor immunity, and a PD-1 ligand, PD-L1, is often overexpressed in tumor cells. Nivolumab binds to the PD-1 receptor to competitively inhibit PD-L1 binding and ultimately disinhibit T-cell activities against cancer cells. Both pembrolizumab and atezolizumab also target the PD-1 signalling pathway.

Nivolumab is available for research purposes under the clone ID: 5C4.B8

Keytruda

Generic name: Pembrolizumab (humanized monoclonal antibody)

Company: Merck & Co and Otsuka Holdings

Protein target: PD-1

Indications: Melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL), urothelial carcinoma (bladder cancer), a cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), gastroesophageal junction (GEJ) cancer, cervical cancer, and hepatocellular carcinoma (liver cancer)

Mechanism of action: Pembrolizumab also competes with PD-L1 for binding to the PD-1 receptor to allow T-cell activities against cancer cells. Pembrolizumab and nivolumab bind to overlapping epitopes on the PD-1 receptor and have many overlapping indications as a result.

Pembrolizumab is available for research purposes from BioVision and Creative Biolabs.

Need an antibody to study PD-1 (human)?

Tecentriq

Generic name: Atezolizumab (fully humanized monoclonal antibody)

Company: Roche

Protein target: PD-L1

Indications: Urothelial carcinoma (bladder cancer) and non-small cell lung cancer (NSCLC)

Mechanism of action: Atezolizumab binds to a PD-1 receptor ligand, PD-L1, to prevent its binding to both PD-1 and B7.1 receptors to restore anti-tumor T-cell activity.

Atezolizumab is available for research purposes from AMSBIO and BioVision

Need an antibody to study PD-L1 (human)?

Monoclonal antibodies targeting key players in inflammation and cancer are expected to be the top-sellers by 2024. But with the current pressure for discounts and the rise of biosimilars to existing biologics, projecting drug sales is a difficult business, so make sure to check back for an update next year.

Do you think this list will change as 2024 approaches?

Have you had success with a particular research antibody against one of these proteins?

Let us know in the comments!
Written By:
Stephanie Prezioso, Ph.D. (she/her)
Topics:

Antibody Applications Therapeutic Antibodies Science

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