Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies

Figures & data

Table 1 Marketed Fc-fusion proteins

International non-proprietary (trade) name	Description	Mode of action	Year/indication of first US approval
Etanercept (Enbrel^®)	75 kDa soluble extracellular domain (ECD) of tumor necrosis factor (TNF) receptor II fused to human IgG1 Fc	Binds membrane-bound and soluble forms of TNF, thereby reducing concentrations of inflammatory cytokines	1998/rheumatoid arthritis
Alefacept (Amevive^®)	First ECD of lymphocyte function-associated antigen 3 (LFA-3) fused to human IgG1 Fc	Binds CD2; blocks the interactions between LFA on APCs with CD2 on T cells, thereby inhibiting T-cell activation	2003/plaque psoriasis
Abatacept (Orencia^®)	ECD of human cytotoxic T lymphocyte associated molecule-4 (CTLA-4) fused to human IgG1 Fc	Blocks the interactions between CD80 or CD86 on APCs and CD28 on T cells, thereby inhibiting T-cell activation	2005/rheumatoid arthritis
Rilonacept (Arcalyst^®)	Two chains, each comprising the C-terminus of the IL-1R accessory protein ligand binding region fused to the N-terminus of the IL-1RI ECD, fused to human IgG1 Fc	Binds IL-1, thereby preventing interaction with endogenous cell-surface receptors	2008/plaque psoriasis
Romiplostim (Nplate^®)	Peptide thrombopoietin (TPO) mimetic fused to the C-terminus of aglycosylated human IgG1 Fc; produced in E. Coli	Binds and agonizes the TPO receptor; Fc functionality minimized due to lack of glycosylation	2008/thrombocytopenia
Belatacept (Nulojix^®)	ECD of CTLA-4 fused to human IgG1 Fc; differs from abatacept by two amino acid substitutions (L104E, A29Y) in the CTLA-4 region	Blocks the interactions between CD80 or CD86 on APCs and CD28 on T cells, thereby inhibiting T-cell activation	2011/prophylaxis of organ rejection in adult kidney transplant recipients
Aflibercept (Eylea™)	ECDs of VEGF receptors 1 and 2 fused to human IgG1 Fc	Binds all forms of VEGF-A, as well as placental growth factor, thereby inhibiting angiogenesis	PDUFA date August 20, 2011/Undergoing review as a treatment for wet age-related macular degeneration as of July 2011