https://orcid.org/0000-0002-1909-5957
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ABSTRACT
The ‘Antibodies to Watch’ article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody–drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14–32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.
Abbreviations
| Aβ | = | amyloid beta |
| ACR20 | = | American College of Rheumatology 20% |
| AD | = | Alzheimer’s disease |
| ADC | = | antibody-drug conjugate |
| ADCC | = | antibody-dependent cell-mediated cytotoxicity |
| 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 |
| BCMA | = | B cell maturation antigen |
| BLA | = | biologics license application |
| BMT | = | bone marrow transplant |
| BTC | = | biliary tract cancer |
| CAPOX | = | capecitabine/oxaliplatin |
| CAR-T | = | chimeric antigenic receptor – T cell |
| CDC | = | complement-dependent cytotoxicity |
| CHMP | = | Committee for Medicinal Products |
| CI | = | confidence interval |
| CLDN18.2 | = | claudin 18.2 |
| CLL | = | chronic lymphocytic leukemia |
| CNS | = | central nervous system |
| COVID-19 | = | coronavirus disease 2019 |
| CR | = | complete response |
| CRSwNP | = | chronic rhinosinusitis with nasal polyps |
| cSCC | = | cutaneous squamous cell carcinoma |
| CTLA-4 | = | cytotoxic T lymphocyte antigen-4 |
| DLBCL | = | diffuse large B-cell lymphoma |
| DM4 | = | N2’-deacetyl-N2’-(4-mercapto-4-methyl-1-oxopentyl) maytansine |
| dMMR | = | deficient mismatch repair |
| EC | = | European Commission |
| EGFR | = | epidermal growth factor receptor |
| EMA | = | European Medicines Agency |
| 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 | = | receptor 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 |
| 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 |
| HSCT | = | hematopoietic stem cell transplant |
| 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 |
| MET | = | mesenchymal epithelial transition factor |
| MM | = | multiple myeloma |
| MMAE | = | monomethyl auristatin E |
| MMR | = | mismatch repair |
| MSI | = | microsatellite instability |
| MTX | = | methotrexate |
| NDA | = | new drug application |
| NHL | = | non-Hodgkin’s lymphoma |
| NIH | = | National Institutes of Health |
| NK | = | natural killer |
| NMPA | = | National Medical Products Administration |
| NSCLC | = | non-small cell lung cancer |
| OR | = | overall response |
| OS | = | overall survival |
| PCSK9 | = | proprotein convertase subtilisin/kexin type 9 |
| PD | = | pharmacodynamics |
| PD-1 | = | programmed cell death protein 1 |
| PD-L1 | = | programmed cell death protein ligand 1 |
| PD-L2 | = | programmed death ligand 2 |
| PFS | = | progression-free survival |
| PNH | = | paroxysmal nocturnal hemoglobinuria |
| PK | = | pharmacokinetics |
| 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 |
| RR | = | relapsed or refractory |
| RSV | = | respiratory syncytial virus, |
| SARS-CoV-2 | = | severe acute respiratory syndrome coronavirus 2 |
| SC | = | subcutaneous |
| scFv | = | single-chain variable fragment |
| T1D | = | type 1 diabetes |
| TCR | = | T cell receptor |
| 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. |
Acknowledgments
The authors thank Hanson Wade for providing access to the Beacon database.
Disclosure statement
HK, LW, and JV are employed by companies that develop antibody therapeutics. SC and JMR are employed by The Antibody Society, a nonprofit trade association funded by corporate sponsors that develop antibody therapeutics or provide services to companies that develop antibody therapeutics. JMR is also Editor-in-Chief of mAbs, a biomedical journal focused on topics relevant to antibody therapeutics development.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2023.2297450