Antibodies to watch in 2022

Abstract

In this 13th annual installment of the annual 'Antibodies to Watch' article series, we discuss key events in commercial antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. Regulatory review of antibody therapeutics that target the SARS-CoV-2 coronavirus proceeded at an unprecedented pace in 2021, resulting in both emergency use authorizations and full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well as others, in numerous countries. As of November 1, a total of 11 antibody therapeutics had been granted first approvals in either the United States or European Union in 2021 (evinacumab, dostarlimab loncastuximab tesirine, amivantamab, aducanumab, tralokinumab, anifrolumab, bimekizumab, tisotumab vedotin, regdanvimab, REGEN-COV2). The first global approvals of seven products, however, were granted elsewhere, including Japan (pabinafusp alfa), China (disitamab vedotin, penpulimab, zimberelimab), Australia (sotrovimab, REGEN-COV2), or the Republic of Korea (regdanvimab). Globally, at least 27 novel antibody therapeutics are undergoing review by regulatory agencies. First actions by the Food and Drug Administration on the biologics license applications for faricimab, sutimlimab, tebentafusp, relatlimab, sintilimab, ublituximab and tezepelumab are expected in the first quarter of 2022. Finally, our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year. Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022.

Keywords: COVID-19; European Medicines Agency; Food and Drug Administration; SARS-CoV-2; antibody therapeutics; cancer; immune-mediated disorders.

Figure 1.

Primary indications for antibody therapeutics approved or in regulatory review in the United States or European Union. Figure based on data publicly available as of November 15, 2021. Total = 131 and includes products that were approved but subsequently withdrawn from the market. Each product is included once; supplemental approvals are not included. Biosimilar and Fc fusion protein products were excluded. Antibodies granted emergency use authorizations (EUAs) or in review for EUAs are not included. Immune-mediated disorders category includes asthma; the genetic disorders are Muckle–Wells syndrome, X-linked hypophosphatemia, hereditary angioedema attacks, and homozygous familial hypercholesterolemia. A searchable table of the figure data is available at .www.antibodysociety.org/antibody-therapeutics-product-data/

Figure 2.

Targets for antibody therapeutics approved or in regulatory review in the United States or European Union for cancer. Figure based on data publicly available as of November 15, 2021. Total = 59 and includes products that were approved but subsequently withdrawn from the market. Bars with hash marks represent bispecific antibodies. Antibodies granted emergency use authorizations (EUAs) or in review for EUAs are not included. Biosimilar and Fc fusion protein products were excluded. A searchable table of the figure data is available at www.antibodysociety.org/antibody-therapeutics-product-data/. Abbreviations: BCMA, B-cell maturation antigen; CTLA-4, cytotoxic T lymphocyte antigen-4, EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; PD-1 programmed cell death protein-1; PDGFR, platelet-derived growth factor receptor; VEGF, vascular endothelial growth factor.

Figure 3.

Targets for antibody therapeutics approved or in regulatory review in the United States or European Union for noncancer indications. Figure based on data publicly available as of November 15, 2021. Total = 72 and includes products that were approved but subsequently withdrawn from the market. Bars with hash marks represent bispecific antibodies. Antibodies granted emergency use authorizations (EUAs) or in review for EUAs are not included. Biosimilar and Fc fusion protein products were excluded. A searchable table of the figure data is available at www.antibodysociety.org/antibody-therapeutics-product-data/. Abbreviations: Ang, angiopoietin; BLys, B lymphocyte stimulator; CGRP, calcitonin gene-related peptide; FGF, fibroblast growth factor; GP, glycoprotein; IGF, insulin-like growth factor; IL, interleukin; MASP-2, mannan-binding lectin-associated serine protease-2, TNF, tumor necrosis factor; RSV, respiratory syncytial virus; VEGF, vascular endothelial growth factor.

Figure 4.

Antibody therapeutics first approved in the United States or European Union each year during 1997–2021. Figure based on data publicly available as of November 15, 2021. Products that were approved but subsequently withdrawn from the market are included in the totals. Antibodies granted emergency use authorizations (EUAs) or in review for EUAs are not included. Biosimilar and Fc fusion protein products were excluded. A searchable table of the figure data is available at .www.antibodysociety.org/antibody-therapeutics-product-data/

Figure 5.

Primary indications for antibody therapeutics in late-stage clinical studies sponsored by commercial firms. ‘Late-stage’ is defined as pivotal Phase 2, Phase 2/3, or Phase 3 studies. Figure based on data publicly available as of November 15, 2021. Immune-mediated disorders category includes allergy and asthma; respiratory includes chronic obstructive pulmonary disease. Antibody therapeutics that have transitioned to regulatory review or been approved in any country, antibody therapeutics for COVID-19, biosimilar antibodies and Fc fusion proteins were excluded.

Figure 6.

Targets for antibody therapeutics in late-stage clinical studies for cancer indications sponsored by commercial firms. ‘Late-stage’ is defined as pivotal Phase 2, Phase 2/3, or Phase 3 studies. Figure based on data publicly available as of November 15, 2021. Antibody therapeutics that have transitioned to regulatory review or been approved in any country, biosimilar antibodies and Fc fusion proteins were excluded. Abbreviations: BCMA, B-cell maturation antigen; CTLA-4, cytotoxic T lymphocyte antigen-4; DLL4, Delta-like ligand 4; GPCR, G-protein coupled receptor; HER, human epidermal growth factor receptor; PD-1 programmed cell death protein-1; PSMA, prostate-specific membrane antigen; TGF, transforming growth factor. See Supplemental Table S1 for additional information about the antibodies.

Figure 7.

Targets for antibody therapeutics in late-stage clinical studies for noncancer indications sponsored by commercial firms. ‘Late-stage’ is defined as pivotal Phase 2, Phase 2/3, or Phase 3 studies. Figure based on data publicly available as of November 15, 2021. Antibody therapeutics that have transitioned to regulatory review or been approved in any country, antibody therapeutics for COVID-19, biosimilar antibodies and Fc fusion proteins were excluded. Abbreviations: HBV, hepatitis B virus; GM-CSF, granulocyte-macrophage colony-stimulating factor; NGF, nerve growth factor; PCSK, proprotein convertase subtilisin/kexin; TF, tissue factor; VEGF, vascular endothelial growth factor. See Supplemental Table S2 for additional information about the antibodies.

Figure 8.

Global commercial clinical pipeline of innovative antibody therapeutics. Figure based on data publicly available as of November 15, 2021. Antibody therapeutics that have transitioned to regulatory review or been approved in any country, biosimilar antibodies and Fc fusion proteins were excluded.