https://orcid.org/0000-0001-6946-4813
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ABSTRACT
There is considerable interest in the pharmaceutical industry toward development of antibody-based biotherapeutics because they can selectively bind diverse receptors and often possess desirable pharmacology. Here, we studied product characteristics of 89 marketed antibody-based biotherapeutics that were approved from 1986 to mid-2020 by gathering publicly available information. Our analyses revealed major trends in their emergence as the best-selling class of pharmaceuticals. Early on, most therapeutic monoclonal antibodies were developed to treat cancer, with CD20 being the most common target. Thanks to industrialization of antibody manufacturing technologies, their use has now blossomed to include 15 different therapeutic areas and nearly 60 targets, and the field is still growing! Drug manufacturers are solidifying their choices regarding types of antibodies and their molecular formats. IgG1 kappa continues to be the most common molecular format among marketed antibody-based biotherapeutics. Most antibody-based biotherapeutics approved since 2015 are either humanized or fully human, but the data we collected do not show a direct correlation between humanness and reported incidence of anti-drug antibodies. Furthermore, there have also been improvements in terms of drug product stability and high concentration liquid formulations suitable for subcutaneous route of administration, which are being approved more often in recent years. These improvements, however, have not been uniformly adopted across all therapeutic areas, suggesting that multiple options for drug product development are being used to serve diverse therapeutic purposes. Insights gained from this analysis may help us devise better end-to-end antibody-based biotherapeutic drug discovery and development strategies.
Abbreviations
| ADA | = | Anti-Drug Antibody |
| ADC | = | Antibody-Drug Conjugate |
| API | = | Active Pharmaceutical Ingredient |
| BiTE | = | Bispecific T-cell Engager |
| CDR | = | Complementarity Determining Region |
| CH | = | Constant region of the heavy chain |
| CL | = | Constant region of the light chain |
| EC | = | European Commission |
| EMA | = | European Medicines Agency |
| EUA | = | Emergency Use Authorization |
| Fab | = | Fragment antigen binding |
| Fv | = | Fragment variable |
| FDA | = | U.S. Food and Drug Administration |
| i.v. | = | Intravenous |
| IgG | = | Immunoglobulin G |
| IgM | = | Immunoglobulin M |
| IGMT | = | The international ImMunoGeneTics information system |
| INN | = | International Nonproprietary Name |
| mAb | = | Monoclonal antibody |
| MM | = | Multiple Myeloma |
| NSCLC | = | Non-small Cell Lung Cancer |
| PD | = | Pharmacodynamics |
| PH20 | = | Recombinant human PH20 hyaluronidase (or rHuPH20) |
| PJIA | = | Polyarticular Juvenile Idiopathic Arthritis |
| PK | = | Pharmacokinetics |
| PS20 | = | Polysorbate 20 |
| PS80 | = | Polysorbate 80 |
| PsA | = | Psoriatic Arthritis |
| QW | = | Once a Week |
| RA | = | Rheumatoid Arthritis |
| s.c. | = | Subcutaneous |
| scFv | = | Single-chain fragment variable |
| sdAb | = | Single-domain antibody |
| SJIA | = | Systematic Juvenile Idiopathic Arthritis |
| TNBC | = | Triple Negative Breast Cancer |
| VH | = | Variable region of the heavy chain |
| VL | = | Variable region of the light chain |
| WHO | = | World Health Organization |
Acknowledgments
KPM thanks Boehringer Ingelheim for postdoctoral fellowship. Authors thank numerous colleagues both within and outside BI for several helpful discussions. Dr. Andrew Nixon is thanked for critical reading of the manuscript. KPM and SK also acknowledge their discussions with Dr. Joschka Bauer, Dr. Anne Karow-Zwick, and Dr. Seema Thakral on the topic of drug formulations. The authors are grateful to anonymous reviewer #1 for very helpful comments on our work.
Disclosure statement
All authors were employees of Boehringer-Ingelheim when this research was performed.
Author contributions
SK and CG formulated the research problem. SK provided day-to-day advice to KPM for this postdoctoral research project. KPM collected all the data and performed analyses. RG and SH helped with interpreting the pharmacology data. All authors contributed toward manuscript writing.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2023.2191301.
Correction Statement
This article has been corrected with minor changes. These changes do not impact the academic content of the article.