Table 1.
Monoclonal antibodies (mAbs) approved by the EMA and FDA for therapeutic use.
| International nonproprietary name (INN) | Target | Type | Year of first FDA approval | Therapeutic indication(s) |
|---|---|---|---|---|
| Avelumab | PD-L1 | Human IgG1/κ | 2017 | Metastatic Merkel cell carcinoma |
| Dupilumab | IL-4Rα | Human IgG4 | 2017 | Asthma; dermatitis |
| Durvalumab | PD-L1 | Human IgG1/κ | 2017 | Metastatic urothelial carcinoma |
| Ocrelizumab | CD20 | Humanized IgG1κ | 2017 | Multiple sclerosis |
| Brodalumab | IL-17RA | Human IgG2/κ | 2017 | Psoriasis |
| Bezlotoxumab | C. difficile toxin B | Human monoclonal antitoxin antibody | 2016 | Enterocolitis; pseudomembranous |
| Adalimumab | TNFα | Human IgG1 | 2016 | Arthritis; juvenile rheumatoid arthritis; psoriatic arthritis; rheumatoid colitis; ulcerative Crohn’s disease; psoriasis; spondylitis; ankylosing |
| Reslizumab | IL-5 | Human IgG4/κ | 2016 | Asthma |
| Olaratumab | PDGFR-α | Human IgG1 | 2016 | Sarcoma |
| Obiltoxaximab | PA component of B. anthracis toxin | Chimeric (mouse/human) IgG1/κ | 2016 | Anthrax infection |
| Infliximab | TNFα | Chimeric human-murine IgG1 | 2016 | Spondylitis; ankylosing; arthritis; rheumatoid colitis; ulcerative arthritis; psoriatic Crohn’s disease; psoriasis |
| Atezolizumab | PD-L1 | Human IgG1 | 2016 | Metastatic non-small cell lung cancer |
| Daratumumab | CD38 | Human IgG1/κ | 2015 | Multiple myeloma |
| Elotuzumab | SLAMF7 | Human IgG1 | 2015 | Multiple myeloma |
| Necitumumab | EGFR | Human IgG1 | 2015 | Carcinoma, non-small-cell lung |
| Secukinumab | Interleukin-17A | Human IgG1/κ | 2015 | Arthritis; psoriatic psoriasis; spondylitis; ankylosing |
| Mepolizumab | IL-5 | Human IgG1/κ | 2015 | Asthma |
| Nivolumab | PD-1 | Human IgG4 | 2015 | Carcinoma; non-small-cell lung carcinoma; renal cell Hodgkin disease melanoma |
| Alirocumab | PCSK9 | Human IgG1 | 2015 | Dyslipidemias |
| Idarucizumab | Dabigatran etexilate | Human FaB | 2015 | Hemorrhage |
| Evolocumab | LDL-C/PCSK9 | Human IgG2 | 2015 | Dyslipidemias; hypercholesterolemia |
| Dinutuximab (1) | GD2 | Human IgG1/κ | 2015 | Neuroblastoma |
| Bevacizumab | CD19 | BiTEs | 2014 | Precursor cell lymphoblastic leukemia–lymphoma |
| Pembrolizumab | PD-1 | Human IgG4 | 2014 | Melanoma |
| Ramucirumab | VEGF | Human IgG1 | 2014 | Stomach neoplasms |
| Vedolizumab | Integrin-α4β7 | HumanizedIgG1 | 2014 | Colitis; ulcerative Crohn’s disease |
| Siltuximab | cCLB8 | Chimeric IgG1κ | 2014 | Giant lymph node hyperplasia |
| Alemtuzumab | CD52 | Humanized IgG1 | 2014 | Multiple sclerosis |
| Trastuzumab emtansine | HER2 | Humanized IgG1 as ADC | 2013 | Breast cancer |
| Obinutuzumab | CD20 | Humanized IgG1 | 2013 | CLL |
| Raxibacumab | Bacillus anthracis protective antigen | Human IgG1 | 2012 | Prevention and treatment of inhalation anthrax |
| Pertuzumab | HER2 | Humanized IgG1 | 2012 | Breast cancer |
| Infliximab | TNF-alpha | Chimeric IgG1 Ab | Not approved (approved in 1997 by EU EMA) | Spondylitis; ankylosing arthritis; rheumatoid colitis; ulcerative Crohn’s disease; arthritis; psoriatic psoriasis |
| Brentuximab | CD30 (conjugate of Mab and MMAE) | Chemeric IgG1 as ADC (antibody drug conjugate) | 2011 | Hodgkin lymphoma (HL), systemic anaplastic large cell lymphoma (ALCL) |
| Belimumab | BLyS | Human IgG1 | 2011 | Systemic lupus erythematosus (SLE) |
| Ipilimumab | CTLA-4 | Human IgG1 | 2011 | Melanoma |
| Denosumab | RANKL | Human IgG2 | 2011 | Prevention of SREs in patients with bone metastases from solid tumors |
| Tocilizumab | IL-6 receptor | Humanized IgG1 | 2010 | Rheumatoid arthritis |
| Denosumab | RANKL | Human IgG2 | 2010 | Osteoporosis |
| Ofatumumab | CD20 | Human IgG1 | 2009 | Chronic lymphocytic leukemia |
| Besilesomab | NCA-95 | Murine IgG1 | Not approved (approved in 1997 by EU EMA) | In vivo diagnosis of inflammation/infection sites via scintigraphic imaging → nontherapeutic |
| Canakinumab | IL-1β | Human IgG1 | 2009 | Cryopyrin-associated periodic syndromes including familial cold autoinflammatory syndrome and Muckle–Wells syndrome; tumor necrosis factor receptor associated periodic syndrome (TRAPS); hyperimmunoglobulin D Syndrome (HIDS)/mevalonate kinase deficiency (MKD) and familial Mediterranean fever (FMF) |
| Golimumab | TNFa | Human IgG1 | 2009 | Rheumatoid arthritis; psoriatic arthritis; ankylosing spondylitis |
| Ustekinumab | IL-12/IL-23 | Human IgG1 | 2009 | Plaque psoriasis |
| Certolizumab pegol | TNFa | Humanized IgG Fab fragment | 2008 | Crohn’s disease; rheumatoid arthritis |
| Catumaxomab | EpCAM and CD3 | Trifunctional MAb IgG2a/IgG2b | Not approved | Malignant ascites in patients with EpCAM-positive carcinomas |
| Eculizumab | Complement C5 | Humanized IgG2/4 | 2007 | Paroxysmal nocturnal hemoglobinuria |
| Ranibizumab | VEGF-A | Humanized IgG1 Fab fragment | 2006 | Neovascular (wet) age-related macular degeneration; macular edema following retinal vein occlusion |
| Panitumumab | EGFR | Human IgG2 | 2006 | Metastatic colorectal carcinoma |
| Catumaxomab | EpCAM | Humanized MAb | 2005 | Head and neck cancer |
| Natalizumab | VLA-4 | Humanized IgG4 | 2004 | Multiple sclerosis (relapsing); Crohn’s disease |
| Cetuximab | EGFR | Chimeric IgG1 | 2004 | Head and neck cancer; colorectal cancer |
| Fanolesomab | CD15 | Murine MAb | 2004 | Imaging of equivocal appendicitis → nontherapeutic |
| Bevacizumab | VEGF | Humanized IgG1 | 2004 | Metastatic colorectal cancer; non-small cell lung cancer; metastatic breast cancer; glioblastoma multiforme; metastatic renal cell carcinoma |
| Omalizumab | IgE | Humanized IgG1 | 2003 | Asthma |
| Tositumomab and iodine 131 tositumomab | CD20 | Murine IgG2a | 2003 | Non-Hodgkin’s lymphoma |
| Efalizumab (2) | CD11a | Humanized IgG1 | 2003 | Psoriasis |
| Ibritumomab tiuxetan | CD20 | Murine IgG1 | 2002 | Non-Hodgkin’s lymphoma |
| Adalimumab | TNFα | Human IgG1 | 2002 | Rheumatoid arthritis; juvenile idiopathic arthritis; psoriatic arthritis; ankylosing spondylitis; Crohn’s disease, plaque psoriasis |
| Alemtuzumab | CD52 | Humanized IgG1 | 2001 | B-cell chronic lymphocytic leukemia |
| Gemtuzumab ozogamicin (3) | CD33 | Humanized IgG4/toxin conjugate | 2000 | Acute myeloid leukemia (AML) |
| Trastuzumab | HER-2 | Humanized IgG1 | 1998 | Breast cancer; metastatic gastric or gastroesophageal junction adenocarcinoma |
| Infliximab | TNFα | Chimeric IgG1 | 1998 | Crohn’s disease; ulcerative colitis; rheumatoid arthritis; ankylosing spondylitis; psoriatic arthritis; plaque psoriasis |
| Basiliximab | CD25 (a chain of IL2 receptor) | Chimeric IgG1 | 1998 | Reversal of transplantation rejection |
| Palivizumab | F-protein of RS virus | Humanized IgG1 | 1998 | Respiratory syncytial virus (RSV) |
| Necitumumab (4) | CD25 (a chain of IL2 receptor) | Humanized IgG1 | 1997 | Reversal of transplantation rejection |
| Rituximab | CD20 | Chimeric IgG1 | 1997 | Non-Hodgkin’s lymphoma; chronic lymphocytic leukemia; rheumatoid arthritis |
| Votumumab (5) | Cytokeratin tumor-associated antigen | Not approved | Detection of carcinoma of the colon or rectum → nontherapeutic | |
| Sulesomab | NCA90 | Murine Fab fragment | Not approved | Diagnostic imaging forosteomyelitis → nontherapeutic |
| Arcitumomab (6) | Human CEA (carcinoembryonic antigen) | Murine Fab fragment | 1996 | Detection of colorectal cancer → nontherapeutic |
| Imiciromab (7) | Human cardiac myosin | Murine Fab fragment | 1996 | Myocardial infarction imaging agent → nontherapeutic |
| Capromab | Tumor surface antigen PSMA | Murine MAb | 1996 | Detection of prostate adenocarcinoma → nontherapeutic |
| Nofetumomab | Carcinoma-associated antigen | Murine Fab fragment | 1996 | Diagnostic imaging of small-cell lung cancer → nontherapeutic |
| Abciximab (8) | GPIIb/IIIa | Chimeric IgG1 Fab | 1994 | High-risk angioplasty (prevention of blood clots) |
| Satumomab | TAG-72 | Murine MAb | 1992 | Detection of colorectal and ovarian cancers → nontherapeutic |
| Muromonab-CD3 | CD3 | Murine IgG2a | 1986 | Transplantation rejection |
(1): Unituxin has been withdrawn from use in the European Union.
(2): Raptiva® was approved in 2003 by the FDA and in 2004 by the EMA. It was voluntarily withdrawn from the market in EU in 2009 and in US in 2009.
(3): Mylotarg® was approved in 2000 by the FDA. It was voluntarily withdrawn from the market in US in 2010.
(4): Zenapax® was approved in 1997 by the FDA and in 1999 by the EMA. It was withdrawn from the market for commercial reasons in EU in 2009 and in US in 2009.
(5): Humaspect® was approved in 1998 by the EMA. It was withdrawn from the market in EU in 2003.
(6): CEA-scan was approved in 1996 by the FDA and by the EMA. It was withdrawn from the market in EU in 2005.
(7): Myoscint® has been discontinued.
(8): Country-specific approval (prior to EMA Centralized Procedure).
PD-L1, Programmed death-ligand 1; IgG1, immunoglubulin G, subclass 1; IL-4Rα, interleukin 4 receptor alpha; IgG4, immunoglubulin G, subclass 4; CD20, B-lymphocyte antigen CD20; IL-17RA, interleukin 17 receptor A; TNFα, tumor necrosis factor alpha; IL-5, interleukin 5; PDGFR-α, platelet-derived growth factor receptor A; PA, protective antigen; CD38, cluster of differentiation 38; SLAMF7, SLAM family member 7; EGFR, epidermal growth factor receptor; PD-1, programmed cell death protein 1; PCSK9, proprotein convertase subtilisin/kexin type 9; FaB, fragment antigen-binding; LDL-C, low-density lipoprotein; PCSK9, proprotein convertase subtilisin/kexin type 9; GD2, disialoganglioside; BiTEs, bi-specific T-cell engagers; VEGF, vascular endothelial growth factor; CD2, cluster of differentiation 2; CD3, cluster of differentiation 3; IgG2a, immunoglubulin G, subclass 2, isotype a; TAG-72, tumor-associated glycoprotein 72; MAb, monoclonal antibody; GPIIb/IIIa, glycoprotein IIb/IIIa; IgG1, immunoglubulin G, subclass 1; PSMA, prostate-specific membrane antigen; NCA90, membrane glycoprotein p95; CD25, interleukin-2 receptor alpha chain; RS, retinoschisin; IL2, interleukin 2; HER-2, human epidermal growth factor receptor 2; CD33, sialic acid binding Ig-like lectin 3; CD52, cluster of differentiation 52; EGFR, epidermal growth factor receptor; VlLA-4, Very Late Antigen-4; EpCAM, epithelial cell adhesion molecule; IL-12, interleukine 12; IL-23, interleukine 23; IL-1β, interleukine 16; RANKL, receptor activator of nuclear factor kappa-B ligand; CTLA4, cytotoxic T-lymphocyte-associated protein 4; BLyS, B lymphocyte stimulator; MMAE, monomethyl auristatin E; LDL-C, low-density lipoprotein; PCSK9, proprotein convertase subtilisin/kexin type 9; SLAMF7, SLAM family member 7; SLAMF7, SLAM family member 7; SRE, skeletal-related events; CLL, chronic lymphocytic leukemia; EMA, European Medicines Agency; FDA, Food and Drug Administration.