Table 5.
Some US FDA-Approved Therapeutic Fusion Proteins
| Approval year | Generic name | Trade name | Key structure | Sponsor | Indication | Mechanism of action |
|---|---|---|---|---|---|---|
| 1998 | Etanercept | Enbrel | Tumor necrosis factor (TNF) receptor fused to IgG1 antibody | Amgen | Rheumatoid arthritis | Interferes with tumor necrosis factor by acting as a TNF inhibitor |
| 1999 | Denileukin diftitox | Ontak | Interleukin-2 fused to diphtheria toxin | Eisai | T-cell lymphoma whose malignant cells express CD25 | Binds to interleukin-2 receptors and introduce diphtheria toxin into cells |
| 2001 | Darbepoetin alfa | Aranesp | Erythropoietin 2 new sites fused with N-linked carbohydrate addition | Amgen | Anemia associated with chronic renal failure | Binds and activates Epo receptor |
| 2001 | Pegylated interferon alfa-2b | PegIntron | IFN-a-2b fused to 12-kD monomethoxy PEG | Merck | Hepatitis C and melanoma | Binds to IFN-a receptor 1 and 2 to affect immuno response and cell apoptosis |
| 2002 | Pegylated interferon alfa-2a | Pegasys | IFN-a-2a fused to monomethoxy PEG | Roche | Hepatitis C and hepatitis B | Binds to IFN-a receptor 1 and 2 to affect immuno response and cell apoptosis |
| 2002 | Pegfilgrastim | Neulasta | Granulocyte colony-stimulating factor fused to PEG | Amgen | Febrile neutropenia | Stimulates the production of white blood cells |
| 2003 | Alefacept | Amevive | Lymphocyte function associated antigen-3 (LFA-3) fused to IgG dimer | Astellas | Moderate to severe chronic plaque psoriasis | Inhibits the binding of endogenous LFA3 to CD2 cells interfering with activation of memory T cells |
| 2005 | Abatacept | Orencia | Interleukin-2 fused to diphtheria toxin | Bristol Myers Squibb | Highly active and progressive rheumatoid arthritis (RA) | Binds to the costimulatory molecules CD80 and CD86 on antigen-presenting cells (APC) |
| 2008 | Rilonacept | Arcalyst | IL-1 receptor extracellular domains fused to the Fc portion of human IgG1 | Regeneron | Familial cold-induced autoinflammatory syndrome (FCAS) | Binds to and neutralizes IL-1 before it can bind to cell surface receptors |
| 2008 | Romiplostim | Nplate | 14 amino-acid peptides fused to the human IgG Fc domain | Amgen | Immune thrombocytopenia | Binds to and activates the thrombopoietin receptor |
| 2011 | Belatacept | Nulojix | ECD of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) fused to human IgG Fc | Bristol Myers Squibb | Post-transplantation lymphoproliferative disorder positive for Epstein-Barr virus (EBV) | Inhibits T-cell activation through costimulation blockade |
| 2012 | Aflibercept | Eylea | ECD of VEGF receptors 1 and 2 fused to human IgG1 Fc | Regeneron | Wet macular degeneration | Binds to circulating VEGFs and acts like a “VEGF trap” |
| 2014 | Albiglutide | Tanzeum | Hormone (glucagon-like peptide-1 dimer albumin fusion) fused to albumin | GlaxoSmithKline | Type 2 diabetes | Acts as an agonist at the GLP-1 receptor which causes an increase of insulin secretion |
| 2014 | Peginterferon beta-1a | Plegridy | IFNb-1b fused to PEG | Biogen Idec | Multiple sclerosis | Interferon beta leads to a reduction of neuron inflammation |
| 2014 | Dulaglutide | Trulicity | GLP-1(7-37) fused to human IgG4 Fc | Eli Lilly | Type 2 diabetes | Binds to glucagon-like peptide 1 receptors and increases insulin secretion by pancreatic beta cells |
| 2015 | Asfotase-alfa | Strensiq | Tissue-nonspecific alkaline phosphatase (TNSALP) fused with hIgG1 Fc | Alexion | Enzyme replacement therapy for onset hypophosphatasia | Replaces TNSALP enzyme which is responsible for formation of an essential mineral in normal bone |
| 2015 | Etanercept-szzs | Erelzi | TNF receptor 2 fused to human IgG1 Fc | Novartis | Autoimmune diseases | Reduces the effect of naturally present TNF |
| 2018 | Tagraxofusp-erzs | Elzonris | Interleukin 3 (IL-3) fused to truncated diphtheria toxin | Stemline Therapeutics | Blastic plasmacytoid dendritic cell neoplasm (BPDCN) | Binds to IL-3 receptors and affects its pathway |
| 2018 | Moxetumomab pasudotox | Lumoxiti | Anti-CD22 antibody fused to PE38 toxin | AstraZeneca | Relapsed or refractory hairy cell leukemia (HCL) | Binds to CD-22 |
| 2019 | Luspatercept | Reblozyl | Human activin receptor type IIb (ActRIIb) linked to IgG1 | Celgene | Anemia in beta thalassemia | Binds TGF superfamily ligands to reduce SMAD signaling |
PEG polyethylene glycol, TNF tumor necrosis factor, TNSALP tissue-nonspecific alkaline phosphatase, SMAD small mothers against decapentaplegic, ECD extracellular ligand-binding domain, VEGF vascular endothelial growth factor