Table 4.
Fusion proteins currently approved for marketing
| US trade name (generic name) | Protein format | Company | Approval date (US) | Molecular target | Major indication | Total sales in 2014 (in US$MM)a | Innovative drug and year of approval |
|---|---|---|---|---|---|---|---|
| Enbrel® (etanercept) | IgG1 Fc fused to p75 exo-domain of TNFR | Immunex (now Amgen) | Nov 2, 1998 | TNF-α | RA | $8,888MM | Innovative |
| Ontak® (denileukin diftitox) | IL-2 fused to diphtheriotoxin; enzyme activity and membrane translocating domain | Eisai | Feb 5, 1999 | IL-2 receptor | Oncology | No information available | Biobetter of Proleukin® (aldesleukin; Chiron, 1992) |
| Amevive® (alefacept) | CD2-binding domain of LFA-3-IgG1 Fc fusion protein | Biogen | Jan 30, 2003; withdrawn in 2011 | Inhibits CD2-LFA-3 on activated T cells | Psoriasis | No information available | Innovative |
| Orencia® (abatacept) | CTLA4-Fc fusion protein-modified Fc | BMS | Dec 23, 2005 | CD80/CD86 | RA | $1,679MM | Innovative |
| Arcalyst® (rilonacept) | IgG1 Fc fusion protein with IL-1 receptor and IL-1 accessory protein in-line | Regeneron | Feb 27, 2008 | Antagonizes IL-1β, IL-1α, IL-1RA | CAPS, Muckle Wells syndrome | $14.4M | Innovative |
| Nplate® (romiplostim) | Fc-peptide fusion (“peptibody”) | Amgen | Aug 22, 2008 | TPO receptor | Thrombo-cytopenia | $491MM | Innovative |
| Elonva® (corifollitropin-α) | FSH-CTP fusion | Merck | No FDA approval; approved by EMA (Feb 1, 2010) | FSH receptor | Fertility | No information available | Biobetter of Humegon® [mentropins FSH, LH (natural)] Organon (1994) |
| Nulojix® (belatacept) | CTLA-4 Fc fusion (higher affinity than abatacept) | BMS | Jun 16, 2011 | CD80/CD86 | Renal trans plantation | No information available | Innovative |
| Eylea® (aflibercept) | VEGFR-Fc fusion | Bayer–Schering Pharma/Regeneron | Nov 18, 2011 | VEGF | Wet AMD; central retinal vein occlusion | $2,775MM | Innovative |
| Zaltrap® (ziv-aflibercept) | VEGFR-Fc fusion | Sanofi/Regeneron | Aug 3, 2012 | VEGF | Metastatic colorectal cancer | $73.3MM | Innovative |
| Alprolix® (eftrenonacog-α; BIIB-029) | rhFactor IX-Fc; Fc domain fused to single molecule of Factor IX (98 kDa) | Biogen Idec/Biovitrum/SOBI | Mar 28, 2014 | Factor substitute | Hemophilia B | $76MM (partial year) | Biobetter of Rixubis® [rhFactor IX; Baxter (2013)] and multiple Factor IX blood product replacement proteins |
| Tanzeum® (US), Eperzan® (EU) (albiglutide; GSK716155; also known as Albugon) | GLP-1-HSA fusion | GSK | Apr 15, 2014 | GLP-1R | T2DM | $8.9MM (partial year) | Biobetter of Victoza® [liraglutide; Novo Nordisk (2010)] |
| Eloctate® (efraloctocog-α) | B-domain-deleted Factor VIII fused to IgG1 Fc (220 kDa) | Biogen Idec/SOBI | Jun 9, 2014 | Factor substitute | Hemophilia A | $58.4MM (partial year) | Biobetter of multiple Factor VIII replacement proteins (e.g., Aafact® (Sanquin, 1995)] |
| Trulicity® (dulaglutide) | GLP-1-Fc fusion protein | Eli Lilly | Sep 18, 2014 | Fc fusion protein; GLP-1 receptor agonist | T2DM | $10.2MM (partial year) | Biobetter of Victoza® [liraglutide; Novo Nordisk (2010)] |
Data obtained from prescribing information released by the manufacturers, company websites, FDA website, and company press releases
AMD age-related macular degeneration, BMS Bristol-Myers Squibb, CAPS cropyrin-associated periodic syndrome, CD cluster of differentiation, CTLA cytotoxic T-lymphocyte-associated protein, CTP carboxyl-terminal peptide (of chorionic gonadotropin β-chain), EMA European Medicines Agency, EU European Union, Fc constant fragment, FDA US Food and Drug Administration, FSH follicle-stimulating hormone, GLP glucagon-like peptide, GSK GlaxoSmithKline, HSA human serum albumin, Ig immunoglobulin, IL interleukin, LFA lymphocyte function-associated antigen, LH luteinizing hormone, MM millions, RA rheumatoid arthritis, rh recombinant human, SOBI Swedish Orphan Biovitrum, T2DM type 2 diabetes mellitus, TNF tumor necrosis factor, TNFR tumor necrosis factor receptor, TPO thrombopoietin, VEGF vascular endothelial growth factor, VEGFR vascular endothelial growth factor receptor
aFrom reference [147]