Antibodies to watch in 2023

ABSTRACT

In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevimab (Beyfortus), mirvetuximab soravtansine (ELAHERE™), and teplizumab (TZIELD)), including 4 bispecific antibodies and 1 ADC. Based on FDA action dates, several additional product candidates could be approved by the end of 2022. An additional seven were first approved in China or Japan in 2022, including two bispecific antibodies (cadonilimab and ozoralizumab). Globally, at least 24 investigational antibody therapeutics are undergoing review by regulatory agencies as of mid-November 2022. Our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline grew by ~20% in the past year to include nearly 140 investigational antibody therapeutics that were designed using a wide variety of formats and engineering techniques. Of those in late-stage development, marketing application submissions for at least 23 may occur by the end of 2023, of which 5 are bispecific (odronextamab, erfonrilimab, linvoseltamab, zanidatamab, and talquetamab) and 2 are ADCs (datopotamab deruxtecan, and tusamitamab ravtansine).

KEYWORDS:

• Antibody therapeutics
• cancer
• COVID-19
• food and drug administration
• european medicines agency
• immune-mediated disorders
• SARS-CoV-2

Acknowledgments

The authors thank Vandna Prasad Rath and Andy Cook at Hanson Wade for providing access to the Beacon Targeted Therapies database.

List of Abbreviations

Aβ, amyloid beta; ACR20, American College of Rheumatology 20%; AD, Alzheimer’s disease; ADC, antibody–drug conjugate; ADCC, antibody-dependent cell-mediated cytotoxicity; ADP, adenosine diphosphate; ALK, anaplastic large-cell lymphoma kinase; AMD, age-related macular degeneration; AML, acute myeloid leukemia; Ang-2, angiopoietin-2; ANGPTL3, angiopoietin-like protein 3; ASCO, American Society of Clinical Oncology; BCG, bacillus Calmette-Guérin; BCMA, B cell maturation antigen; BCVA, Best-corrected visual acuity; BLA, biologics license application; BMS, Bristol Myers Squibb; BMT, bone marrow transplant; BTC, biliary tract cancer; CAD, cold agglutinin disease; CAPOX, capecitabine/oxaliplatin; CAR-T, Chimeric Antigenic Receptor – T cell; CDC, complement-dependent cytotoxicity; CDR-SB, Clinical Dementia Rating Scale – Sum of Boxes; CHMP, Committee for Medicinal Products for Human Use; CI, confidence interval; CLDN18.2, claudin 18.2; CLL, chronic lymphocytic leukemia; CMC, Chemistry, Manufacturing and Controls; CNS, central nervous system; COVID-19, coronavirus disease 2019; CR, complete response; CRS, cytokine release syndrome, CSCC, cutaneous squamous cell carcinoma; CSU, chronic spontaneous urticaria; CTLA-4, cytotoxic T lymphocyte antigen-4; DCR, disease control rate; DLBCL, diffuse large B-cell lymphoma; DM4, N2’-deacetyl-N2’-(4-mercapto-4-methyl-1-oxopentyl) maytansine; DME, diabetic macular edema; dMMR, deficient mismatch repair; EC, European Commission; ECMO, extracorporeal membrane oxygenation; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ENKTL, extranodal natural killer/T-cell lymphoma; EpCAM, epithelial cell adhesion molecule; ESCC, esophageal squamous cell carcinoma; ESMO, European Society for Medical Oncology; EU, European Union; EUA, Emergency use authorization; Fab, antigen-binding fragment; Fc, crystallizable fragment; FcyR, Receptors for IgG Fc; FcRn, neonatal Fc receptor; FDA, US Food and Drug Administration; FL, follicular lymphoma; FRα, folate receptor alpha; GEA, gastroesophageal adenocarcinoma; GEJ, gastroesophageal junction; GM-CSF, granulocyte-macrophage colony stimulating factor; GPP, generalized pustular psoriasis; GPRC5D, G Protein-Coupled Receptor Class C Group 5 Member D; GvHD, graft-vs-host disease; HCC, hepatocellular carcinoma; HER2, human epidermal growth factor receptor 2; HLA, human leukocyte antigen; HoFH, homozygous familial hypercholesterolemia; HR, hazard ratio; HS, hidradenitis suppurativa; HSCT, hematopoietic stem cell transplant; hTfR, human transferrin receptor; iADRS, Integrated AD Rating Scale; IDS, iduronate-2-sulfatase; IFN, interferon; IFNAR1, interferon alpha receptor 1; IGA, Investigator’s Global Assessment; IgE, immunoglobulin E; IgG, immunoglobulin G; IL, interleukin; IM, intramuscular; INN, International Nonproprietary Names; IRRC, independent radiology review committee; IV, intravenous; LAG-3, lymphocyte-activation gene 3; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; LM, leptomeningeal metastases; MAA, marketing authorization application; mAb, monoclonal antibody; MASP-2, mannan-binding lectin-associated serine protease-2; MDS, myelodysplastic syndrome; MET, mesenchymal epithelial transition factor; MHLW, Ministry of Health, Labor and Welfare; MM, multiple myeloma; MMAE, monomethyl auristatin E; MMR, mismatch repair; MPS-II, mucopolysaccharidosis II; MS, multiple sclerosis; MSI, microsatellite instability; MTX, methotrexate; NDA, new drug application; NHL, non-Hodgkin’s lymphoma; NIH, National Institutes of Health; NK, natural killer cells; NMIBC, non-muscle invasive bladder cancer; NPDR, non-proliferative diabetic retinopathy; NMPA, National Medical Products Administration; NSCLC, non-small cell lung cancer; OA, osteoarthritis; OR, overall response; OS, overall survival; PD, pharmacodynamics; PD-1, programmed cell death protein 1; PD-L1, programmed cell death protein ligand 1; PD-L2, programmed death ligand 2; PDUFA, Prescription Drug User Fee Act; PFS, progression-free survival; PHN, paroxysmal nocturnal hemoglobinuria; PK, pharmacokinetics; PMDA, Pharmaceuticals and Medical Devices Agency; PR, partial response; PRIME, Priority Medicines; PTCL, peripheral T cell lymphoma; PTI, personalized treatment intervals; RA, rheumatoid arthritis; RECIST, Response Evaluation Criteria in Solid Tumors; RSV, respiratory syncytial virus, RT-qPCR, Quantitative reverse transcription PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SC, subcutaneous; SCAC, squamous cell carcinoma of the anal canal; scFv, single-chain variable fragment; SLE, systemic lupus erythematosus; T1D, type 1 diabetes; TCR, T cell receptor; TGA, Australian Therapeutic Goods Administration; TIGIT, T-cell Immunoreceptor with Ig and ITIM domains; TIM-3, T-cell immunoglobulin and mucin-domain domain-containing molecule-3; TMAs, thrombotic microangiopathies; TNF, tumor necrosis factor; UK, United Kingdom; US, United States; VEGF, human vascular endothelial growth factor; VHH, variable heavy chain single-domain antibodies

Disclosure statement

HK and JV are employed by companies that develop antibody therapeutics. JMR is employed by The Antibody Society, a non-profit trade association funded by corporate sponsors that develop antibody therapeutics or provide services to companies that develop antibody therapeutics, and she is Editor-in-Chief of mAbs, a biomedical journal focused on topics relevant to antibody therapeutics development. Data in this publication were collected from publicly available sources.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2022.2153410

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.