Table 1 Biopharmaceuticals approved in the United States and European Union through end of July 2018

From: Biopharmaceutical benchmarks 2018

ProductCompany (location)Therapeutic indicationDate approved
Recombinant clotting factors
Factor VIII
Adynovi (rurioctocog alfa pegol), extended half-life PEGylated form of full-length r factor VIII product Advate (see below). Same product as Adynovate (see below)Baxalta Innovations (Vienna)Hemophilia A2018 (EU)
Afstyla (lonoctocog alfa), B-domain-truncated rh coagulation factor VIII, produced in CHO cellsCSL Behring (Marburg, Germany, & Kankakee, IL, USA)Hemophilia A2017 (EU) 2016 (US)
Vihuma (simoctocog alfa), rh B-domain-deleted factor VIII, produced in HEK cells. Same product as Nuwiq (see below)Octapharma (Stockholm)Hemophilia A2017 (EU)
Iblias (octocog alfa), rh coagulation factor VIII, produced in BHK cells using the same expression construct as Bayer's Kogenate and Helixate. Same product as Kovaltry (see below)Bayer Pharma (Berlin)Hemophilia A2016 (EU)
Kovaltry (octocog alfa), rh coagulation factor VIII, produced in BHK cells using the same expression construct as Bayer's Kogenate and Helixate. Same product as Iblias (see above)Bayer Pharma Bayer Health Care (Whippany, NJ, USA)Hemophilia A2016 (EU & US)
Vonvendi (von Willebrand factor (recombinant)), produced in CHO cellsBaxalta (Westlake Village, CA, USA)von Willebrand disease2015 (US)
Nuwiq (simoctocog alfa), B-domain-deleted rh factor VIII, produced in HEK cells. Same product as Vihuma (see above)Octapharma USA (Hoboken, NJ, USA) OctapharmaHemophilia A2015 (US) 2014 (EU)
Obizur (susoctocog alfa), r B-domain-deleted porcine factor VIII, produced in BHK cellsBaxalta Innovations Baxter Healthcare (Westlake Village, CA, USA)Acquired hemophilia due to development of autoantibodies against factor VIII2015 (EU) 2014 (US)
Adynovate (recombinant, PEGylated antihemophilic factor), extended half-life PEGylated form of full-length r factor VIII product Advate (see below). Same product as Adynovi (see above)BaxaltaHemophilia A2015 (US)
Elocta (efmoroctocog alfa) in EU, Eloctate (antihemophilic factor recombinant, Fc fusion protein) in US: rh coagulation factor VIII–Fc fusion protein comprising B-domain-deleted human factor VIII covalently linked to the Fc domain of a human IgG, produced in HEK cellsSwedish Orphan Biovitrum (Stockholm) Biogen Idec (Cambridge, MA, USA)Hemophilia A2015 (EU) 2014 (US)
NovoEight (turoctocog alfa), rh factor VIII analog that, when activated, is structurally comparable to endogenous human factor VIIIa, produced in CHO cellsNovo Nordisk (Bagsvaerd, Denmark, & Plainsboro, NJ, USA)Hemophilia A2013 (EU & US)
Xyntha (antihemophilic factor), rh coagulation factor VIII, produced in CHO cellsPfizer/Wyeth (Philadelphia)Hemophilia A2008 (US)
Advate (octocog alfa), rh factor VIII, produced in CHO cellsBaxter Healthcare (Vienna & Deerfield, IL, USA)Hemophilia A2004 (EU)
2003 (US)
Helixate NexGen (octocog alfa), rh factor VIII, produced in BHK cellsBayer (Berlin)Hemophilia A2000 (EU)
ReFacto (moroctocog alfa), B-domain-deleted rh factor VIII, produced in CHO cellsPfizer/Wyeth (Sandwich, UK) Genetics Institute (Cambridge, MA, USA)Hemophilia A2000 (US)
1999 (EU)
Kogenate, Helixate (antihemophilic factor), rh factor VIII, produced in BHK cells. Sold as Helixate by Aventis Behring through a license agreementBayer (Leverkusen, Germany, & Berkeley, CA, USA)Hemophilia A2000 (EU)
1993 (US)
Bioclate (antihemophilic factor), rh factor VIII, produced in CHO cellsAventis Behring (King of Prussia, PA, USA)Hemophilia A1993 (US)
Recombinate (antihemophilic factor), rh factor VIII, produced in CHO cellsBaxter Healthcare (Deerfield, IL, USA), Genetics InstituteHemophilia A1992 (US)
Other blood factors
Andexxa (coagulation factor Xa recombinant inactivated-zhzo), r modified human factor Xa, produced in CHO cellsPortola Pharmaceuticals (South San Francisco, CA, USA)For patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding2018 (US)
Rebinyn (rh coagulation factor IX) in US, Refixia (nonacog beta pegol) in EU: rh coagulation factor IX, produced in CHO cells and PEGylatedNovo NordiskHemophilia B2017 (EU & US)
Alprolix (eftrenonacog alfa), rh coagulation factor IX fused to a human IgG1 Fc domain, produced in HEK cellsBiogen Idec (Maidenhead, UK, & Cambridge, MA, USA)Hemophilia B2016 (EU) 2014 (US)
Idelvion (albutrepenonacog alfa), rh factor IX–albumin fusion protein, produced in CHO cellsCSL BehringHemophilia B2016 (EU & US)
Ixinity (coagulation factor IX (recombinant)), rh coagulation factor IX, produced in CHO cellsAptevo BioTherapeutics (Berwyn, PA, USA)Hemophilia B2015 (US)
Rixubis (nonacog gamma), rh factor IX, produced in CHO cellsBaxalta Innovations (Vienna) Baxter Healthcare (Westlake Village, CA, USA)Hemophilia B2014 (EU) 2013 (US)
Tretten in US, Novothirteen in EU (catridecog), rh factor XIII A-subunit, produced in S. cerevisiaeNovo NordiskCongenital factor XIII A-subunit deficiency2013 (US)
2012 (EU)
Recothrom (thrombin), rh factor IIa, produced in CHO cellsZymoGenetics (Seattle)Control of minor bleeding during surgery2008 (US)
NovoSeven (eptacog alfa, activated), rh factor VIIa, produced in BHK cellsNovo NordiskSome forms of hemophilia1996 (EU)
1999 (US)
Benefix (nonacog alfa), rh factor IX, produced in CHO cellsPfizer/WyethHemophilia B1997 (EU & US)
Recombinant thrombolytics, anticoagulants and other blood-related products
Tissue plasminogen activator
Metalyse (tenecteplase), modified rh tPA, produced in CHO cellsBoehringer Ingelheim (Ingelheim, Germany)Myocardial infarction2001 (EU)
Withdrawn 2005
TNKase (tenecteplase), modified rh tPA, produced in CHO cellsRoche/Genentech (South San Francisco, CA, USA)Myocardial infarction2000 (US)
Ecokinase (reteplase), r tPA, produced in Escherichia coli; differs from human tPA in that 3 of its 5 domains have been deletedRoche (Welwyn Garden City, UK)Acute myocardial infarction1996 (EU)
Withdrawn 2000
Rapilysin (reteplase), r tPA (see Ecokinase above)Actavis Group PTC (Hafnarfjordur, Iceland), RocheAcute myocardial infarction1996 (EU)
Retavase (reteplase), r tPA (see Ecokinase above)Chiesi USA (Cary, NC, USA)Acute myocardial infarction1996 (US)
Activase (alteplase), rh tPA, produced in CHO cellsRoche/GenentechAcute myocardial infarction1987 (US)
Hirudin
Refludan (lepirudin), r hirudin, produced in S. cerevisiaeCelgene Europe (Windsor, UK) Bayer HealthCareAnticoagulation therapy for heparin-associated thrombocytopenia1997 (EU)
1998 (US)
Withdrawn 2012 (EU)
Revasc (desirudin), r hirudin, produced in S. cerevisiaeCanyon Pharmaceuticals (London)Prevention of venous thrombosis1997 (EU)
Withdrawn 2014
Other
Ruconest (conestat alfa), rh C1 esterase inhibitor, produced in the milk of transgenic rabbitsSantarus (Raleigh, NC, USA) Pharming Group (Leiden, the Netherlands)Acute angioedema2014 (US) 2010 (EU)
Jetrea (ocriplasmin), r truncated form of human plasmin, produced in Pichia pastorisThromboGenics (Leuven, Belgium)Symptomatic vitreomacular adhesion, vitreomacular traction2013 (EU)
2012 (US)
Atryn (rh antithrombin), produced in milk of transgenic goatsLaboratoire français du fractionnement et des biotechnologies (Les Ulis, France), rEVO Biologics (Framingham, MA, USA)Hereditary antithrombin deficiency2009 (US)
2006 (EU)
Kalbitor (ecallantide), plasma kallikrein inhibitor, produced in P. pastorisDyax (Cambridge, MA, USA)Hereditory angioedema2009 (US)
Xigris (drotrecogin alfa), rh activated protein C, produced in a human cell lineEli Lilly (Houten, the Netherlands)Severe sepsis2001 (US)
2002 (EU)
Withdrawn 2012 (EU)
Recombinant hormones
Insulins
Semglee (insulin glargine), r insulin glargine, produced in P. pastoris, biosimilar to LantusMylan (Saint-Priest, France)Diabetes mellitus2018 (EU)
Admelog (insulin lispro injection), rapid-acting human insulin analog, produced in E. coliSanofi (Bridgewater, NJ, USA)Diabetes mellitus2017 (US)
Fiasp (insulin aspart injection), rapid-acting insulin analog, produced in S. cerevisiaeNovo NordiskDiabetes mellitus2017 (US)
Insulin lispro Sanofi, produced in E. coli, biosimilar to HumalogSanofi-Aventis (Paris)Diabetes mellitus2017 (EU)
Lusduna (insulin glargine), engineered insulin, produced in E. coli, biosimilar to LantusMerck Sharp & Dohme (Hoddesdon, UK)Diabetes mellitus2017 (EU) 2017 (US, tentative)
Suliqua in EU, Soliqua in US (insulin glargine/lixisenatide), combination of long-acting insulin glargine, produced in E. coli, and a synthetically produced human GLP-1 analogSanofi-Aventis (Paris) Sanofi (Bridgewater, NJ, USA)Diabetes mellitus type 22017 (EU) 2016 (US)
Xultophy (insulin degludec/liraglutide), a combination of 2 previously approved products, Victoza and TresibaNovo NordiskDiabetes mellitus type 22016 (US) 2014 (EU)
Abasaglar (previously Abasria) in EU, Basaglar in US (insulin glargine), produced in E. coli, biosimilar (in EU) to LantusEli Lilly (Indianapolis), Boehringer Ingelheim (Ridgefield, CT, USA) Eli Lilly (Vienna)Diabetes mellitus2015 (US) 2014 (EU)
Ryzodeg 70/30 in US, Ryzodeg in EU (insulin degludec/insulin aspart), combination of two engineered insulins, produced in S. cerevesiaeNovo NordiskDiabetes mellitus type 1 and 22015 (US) 2013 (EU)
Toujeo (insulin glargine), produced in E. coliSanofi (Bridgewater, NJ, USA)Diabetes mellitus2015 (US)
Tresiba (insulin degludec), engineered long-acting human insulin analog, produced in S. cerevisiae (see also Ryzodeg above)Novo NordiskDiabetes mellitus type 1 and 22015 (US) 2013 (EU)
Afrezza (rh insulin), produced in E. coliMannKind (Danbury, CT, USA)Diabetes mellitus2014 (US)
Novolog mix (insulin aspart mix), a 50:50 mixture of engineered rh insulin, produced in S. cerevisiae in soluble and protamine suspension formsNovo NordiskDiabetes mellitus2008 (US)
Insulin Human Winthrop (rh insulin), produced in E. coliSanofi (Frankfurt)Diabetes mellitus2007 (EU)
Withdrawn 2018
Exubera (inhalable rh insulin), produced in E. coliPfizer (Sandwich, UK)Diabetes mellitus2006 (EU & US)
Withdrawn 2008 (EU)
Levemir (insulin detemir), long-acting rh insulin, produced in S. cerevisiaeNovo NordiskDiabetes mellitus2005 (US)
2004 (EU)
Apidra (insulin glulisine), rapid-acting insulin analog, produced in E. coliSanofi (Frankfurt)Diabetes mellitus2004 (EU & US)
Actrapid, Velosulin, Monotard, Insulatard, Protaphane, Mixtard, Actraphane, Ultratard: rh insulin formulated as short-, intermediate- or long-acting product, produced in S. cerevisiaeNovo NordiskDiabetes mellitus2002 (EU)
Monotard and Ultratard withdrawn 2006
Velosulin withdrawn 2009
Novolog (insulin aspart), short-acting rh insulin analog, produced in S. cerevisiaeNovo NordiskDiabetes mellitus2001 (US)
Novolog mix 70/30 (contains insulin aspart, a short-acting rh insulin analog, in both soluble and crystalline form) (see also Novomix 30 below)Novo NordiskDiabetes mellitus2001 (US)
Novomix 30 (contains a mixture of insulin aspart, a short-acting rh insulin analog, in both soluble and crystalline form, produced in S. cerevisiae)Novo NordiskDiabetes mellitus2000 (EU)
Lantus (insulin glargine), long-acting rh insulin analog, produced in E. coliSanofi (Frankfurt)Diabetes mellitus2000 (EU & US)
Optisulin (insulin glargine), long-acting rh insulin analog, produced in E. coli (see also Lantus above)Sanofi (Frankfurt)Diabetes mellitus2000 (EU)
NovoRapid (insulin aspart), rh insulin analog), produced in S. cerevisiaeNovo NordiskDiabetes mellitus1999 (EU)
Liprolog (insulin lispro), insulin analog, produced in E. coliEli Lilly (Houten, the Netherlands)Diabetes mellitus1997 (EU)
Withdrawn 2001
Insuman (rh insulin), produced in E. coliSanofi (Frankfurt)Diabetes mellitus1997 (EU)
Humalog (insulin lispro), insulin analog, produced in E. coliEli Lilly (Houten, the Netherlands)Diabetes mellitus1996 (EU & US)
Novolin (rh insulin), produced in S. cerevisiaeNovo NordiskDiabetes mellitus1991 (US)
Withdrawn 2010
Humulin (rh insulin), produced in E. coliEli Lilly (Indianapolis)Diabetes mellitus1982 (US)
Human growth hormone
Somatropin Biopartners (somatropin), r hGH, produced in S. cerevisiaeBiopartners (Reutlingen, Germany)Growth failure, growth hormone deficiency2013 (EU)
Withdrawn 2017
Accretropin (somatropin), r hGH, produced in E. coliEmergent Biosolutions (Rockville, MD, USA) Cangene (Winnipeg, MB, Canada)Growth failure or short stature associated with Turner syndrome in children2008 (US)
Valtropin (somatropin), r hGH, produced in S. cerevisiae, biosimilar to HumatropeBiopartners
LG Life Sciences (Reutlingen, Germany)
Certain forms of growth disturbance in children and adults2007 (US)
2006 (EU)
Withdrawn 2012 (EU)
Omnitrope (somatropin), r hGH, produced in E. coli, biosimilar (in EU) to GenotropinSandoz (Kundl, Austria) Novartis (Princeton, NJ, USA)Certain forms of growth disturbance in children and adults2006 (EU & US)
Somavert (pegvisomant), PEGylated r hGH analog (antagonist), produced in E. coliPfizer (Brussels & New York) Nektar Therapeutics (San Francisco)Acromegaly2003 (US)
2002 (EU)
Nutropin AQ (somatropin), r hGH, produced in E. coli, different formulation of Nutropin (see below)Ipsen Pharma (Boulogne-Billancourt, France)Growth failure, Turner syndrome2001 (EU)
1994 (US)
Withdrawn 2008 (EU)
Serostim (somatropin), r hGH, produced in mouse C127 cellsEMD Serono (Geneva)AIDS-associated catabolism and wasting1996 (US)
Saizen (somatropin), r hGH, produced in mouse C127 cellsEMD Serono (Rockland, MA, USA)hGH deficiency in children1996 (US)
Genotropin (somatropin), r hGH, produced in E. coliPfizer (New York)hGH deficiency in children1995 (US)
Norditropin (somatropin), r hGH, produced in E. coliNovo NordiskGrowth failure in children due to inadequate growth hormone secretion1995 (US)
Tev-Tropin, Bio-tropin (somatropin), r hGH, produced in E. coliTeva Pharmaceuticals (North Wales, PA, USA)hGH deficiency in children1995 (US)
Nutropin (somatropin), r hGH, produced in E. coliRoche/GenentechhGH deficiency in children1994 (US)
Humatrope (somatropin), r hGH, produced in E. coliEli Lilly (Indianapolis)hGH deficiency in children1987 (US)
Protropin (somatrem), r hGH differing from hGH by an extra N-terminal methionine, produced in E. coliGenentechhGH deficiency in children1985 (US)
Withdrawn 2004
Follicle-stimulating hormone
Rekovelle (follitropin delta), rh FSH, produced in PER.C6 cellsFerring Pharmaceuticals (Copenhagen)Anovulation2016 (EU)
Bemfola (follitropin alfa), rh FSH, produced in CHO cells, biosimilar to Gonal FFinox Biotech (Burgdorf, Switzerland)Anovulation (women), failure of spermatogenesis (men)2014 (EU)
Ovaleap (follitropin alfa), rh FSH, produced in CHO cells, biosimilar to Gonal FTeva Pharma (Utrect, the Netherlands)Infertility, subfertility2013 (EU)
Elonva (corifollitropin alfa), a modified rh FSH in which the C-terminal peptide of the β-subunit of human chorionic gonadotropin is fused to the FSH β-chain, produced in CHO cellsMerck Sharp & DohmeControlled ovarian stimulation2010 (EU)
Fertavid (follitropin beta), rh FSH, produced in CHO cells. Active substance same as that in Puregon (see below)Merck Sharp & DohmeInfertility2009 (EU)
Pergoveris (follitropin alfa/lutropin alfa) combination product containing rh FSH and rh luteinizing hormone, both produced in CHO cellsMerck Serono (London)Stimulation of follicular development in women with severe luteinizing hormone and FSH deficiency2007 (EU)
Follistim (follitropin beta), rh FSH, produced in CHO cellsMerck (Whitehouse Station, NJ, USA)Infertility1997 (US)
Puregon (follitropin beta), rh FSH, produced in CHO cellsMerck Sharp & Dohme (Haarlem, the Netherlands)Anovulation and superovulation1996 (EU)
Gonal F (follitropin alfa), rh FSH, produced in CHO cellsMerck Serono EMD Serono (Rockland, MD, USA)Anovulation and superovulation1997 (US)
1995 (EU)
Other hormones
Myalepta in EU, Myalept in US (metreleptin), rh leptin analog, produced in E. coliAegerion Pharmaceuticals (Amsterdam & Cambridge, MA, USA)Some forms of lipodystrophy2018 (EU) 2014 (US)
Ozempic (semaglutide), human GLP-1 receptor agonist, produced in yeast and covalently modified by attachment of a C18 fatty acidNovo NordiskDiabetes mellitus type 22018 (EU) 2017 (US)
Movymia (teriparatide), rh parathyroid hormone fragment, produced in E. coli, biosimilar to Fortseo. Same product as Terrosa (see below)STADA Arzneimittel (Bad Vilbel, Germany)Osteoporosis2017 (EU)
Natpar (parathyroid hormone), rh parathyroid hormone, full length, produced in E. coli. Same product as Preotact (see below).Shire Pharmaceuticals Ireland (Dublin)Hypoparathyroidism2017 (EU)
Terrosa (teriparatide), rh parathyroid hormone fragment, produced in E. coli, biosimilar to Fortseo. Same product as Movymia (see above)Gedeon Richter (Budapest)Osteoporosis2017 (EU)
Natpara (parathyroid hormone), rh parathyroid hormone, produced in E. coliShire-NPS Pharmaceuticals (Lexington, MA, USA)Hypocalcemia2015 (US)
Saxenda (liraglutide), human GLP-1 analog, produced in S. cerevisiae and covalently modified by palmitic acid. Active substance same as that in Victoza (see below)Novo NordiskObesity2015 (EU)
Eperzan in EU, Tanzeum in US (albiglutide), GLP-1 receptor agonist: two tandem copies of modified human GLP-1 fused to human albumin, produced in S. cerevisiaeGSK (Carrigaline, Ireland, & Research Triangle Park, NC, USA)Diabetes mellitus type 22014 (EU & US)
Trulicity (dulaglutide), fusion protein consisting of a GLP-1 analog linked to a human IgG Fc domain, produced in a mammalian cell lineEli Lilly (Utrecht, the Netherlands, & Indianapolis)Diabetes mellitus type 22014 (EU & US)
Gattex in US, Revestive in EU (teduglutide), rh GLP-2 analog, produced in E. coliNPS Pharma (Dublin)Short bowel syndrome2012 (EU & US)
Victoza (liraglutide), GLP-1 analog with attached fatty acid, produced in S. cerevisiaeNovo NordiskDiabetes mellitus type 22010 (US)
2009 (EU)
Preotact, rh parathyroid hormone, produced in E. coliNPS PharmaOsteoporosis2006 (EU)
Withdrawn 2014
Fortical, r salmon calcitonin, produced in E. coliUpsher-Smith Laboratories (Minneapolis) Unigene Laboratories (Fairfield, NJ, USA)Postmenopausal osteoporosis2005 (US)
Luveris (lutropin alfa), rh luteinizing hormone, produced in CHO cellsEMD Serono (Rockland, MA, USA) Merck Europe (Amsterdam)Some forms of infertility2004 (US)
2000 (EU)
Forsteo in EU, Forteo in US (teriparatide), r shortened human parathyroid hormone, produced in E. coliEli Lilly (Houten, the Netherlands)Established osteoporosis in some postmenopausal women2003 (EU)
2002 (US)
Natrecor (nesiritide), rh natriuretic peptide, produced in E. coliJohnson & Johnson/Scios (Titusville, NJ, USA)Acutely decompensated congestive heart failure2001 (US)
Ovitrelle in EU, Ovidrel in US (choriogonadotropin alfa) rh chorionic gonadotropin, produced in CHO cellsMerck SeronoSelected assisted reproductive techniques2001 (EU)
2000 (US)
Thyrogen (thyrotropin alfa), rh thyroid-stimulating hormone, produced in CHO cellsSanofi Genzyme (Cambridge, MA, USA)Thyroid cancer (detection and treatment)1998 (US)
2000 (EU)
Forcaltonin, r salmon calcitonin, produced in E. coliUnigene UK (Bushey Heath, UK)Paget disease1999 (EU)
Withdrawn 2008
Glucagen, rh glucagon, produced in S. cerevisiaeNovo NordiskHypoglycemia1998 (US)
Glucagon (glucagon, recombinant), rh glucagon, produced in E. coliEli Lilly (Indianapolis)Hypoglycemia1998 (US)
Recombinant growth factors
Erythropoietin
Retacrit (epoetin zeta in EU, epoetin alfa-epbx in US), rh EPO, produced in CHO cells, biosimilar to Eprex and ErypoHospira (Royal Leamington Spa, UK) Pfizer (Lake Forest, IL, USA)Anemia2018 (US) 2007 (EU)
Biopoin (epoetin theta), rh EPO, produced in CHO cellsTeva (Ulm, Germany)Anemia2009 (EU)
Eporatio (epoetin theta), rh EPO, produced in CHO cellsTeva (Ulm, Germany)Anemia2009 (EU)
Abseamed (epoietin alfa), produced in CHO cells, biosimilar to Eprex/ErypoMedice Arzneimittel Pütter (Iserlon, Germany)Anemia associated with chronic renal failure2007 (EU)
Binocrit (epoetin alfa), produced in CHO cells, biosimilar to Eprex/ErypoSandozAnemia associated with chronic renal failure2007 (EU)
Epoetin alfa Hexal (epoietin alfa), produced in CHO cells, biosimilar to Eprex/ErypoHexal (Holzkirchen, Germany)Anemia associated with chronic renal failure2007 (EU)
Mircera (methoxy polyethylene glycol-epoetin beta) PEGylated rh EPO, produced in CHO cellsRoche (Welwyn Garden City, UK)Anemia associated with chronic kidney disease2007 (EU & US)
Silapo (epoetin zeta), produced in CHO cells, biosimilar to Eprex/ErypoSTADA (Bad Vilbel, Germany) yesAnemia associated with chronic renal failure2007 (EU)
Dynepo (epoetin delta), rh EPO, produced in a human cell lineShire Pharmaceuticals (Basingstoke, UK)Anemia2002 (EU)
Withdrawn 2009
Aranesp (darbepoetin alfa), long-acting r EPO analog, produced in CHO cells (see Nespo below)Amgen (Breda, the Netherlands)Anemia2001 (EU & US)
Nespo (darbepoetin alfa), long-acting r EPO analog, produced in CHO cells (see Aranesp above)Dompé Biotec (Milan)Anemia2001 (EU)
Withdrawn 2008
Neorecormon (epoietin beta), rh EPO, produced in CHO cellsRocheAnemia1997 (EU)
Procrit (epoietin alfa), rh EPO, produced in a mammalian cell lineJanssen Biotech (Horsham, PA, USA)Anemia1990 (US)
Epogen (epoietin alfa), rh EPO, produced in CHO cellsAmgenAnemia1989 (US)
Colony-stimulating factors
Fulphila (pegfilgrastim-jmdb), PEGylated rh G-CSF, produced in E. coli, biosimilar to NeulastaMylan (Rockford, IL USA)Neutropenia2018 (US)
Nivestym (filgrastim-aafi) in US, Nivestim (filgrastim) in EU: rh G-CSF, produced in E. coli, biosimilar to NeupogenPfizer (Lake Forest, IL, USA) Hospira (Royal Leamington Spa, UK)Neutropenia2018 (US) 2010 (EU)
Ristempa (pegfilgrastim), covalent conjugate of rh G-CSF, produced in E. coli and conjugated to 20-kDa polyethylene glycolAmgen (Breda, the Netherlands)Neutropenia2015 (EU) Withdrawn 2017
Zarxio in US, Zarzio in EU (filgrastim-sndz), rh G-CSF, produced in E. coliSandoz (Princeton, NJ, USA, & Kundl, Austria)Neutropenia2015 (US) 2009 (EU)
Accofil (filgrastim), G-CSF, produced in E. coli, biosimilar to Neupogen. Same product as Grastofil (see below)Accord Healthcare (Ahmedabad, India)Neutropenia2014 (EU)
Grastofil (filgrastim), rh G-CSF, produced in E. coli, biosimilar to Neupogen. Same product as Accofil (see above)Apotex (Leiden, the Netherlands)Neutropenia2013 (EU)
Lonquex (lipegfilgrastim), PEGylated rh G-CSF, produced in E. coliTeva Pharma (Utrect, the Netherlands)Neutropenia2013 (EU)
Granix (tbo-filgrastim), rh G-CSF, produced in E. coli. Same product as Tevagrastim (see below)Teva Pharmaceuticals USA (Frazer, PA, USA) Cephalon (Malvern, PA, USA)Neutropenia2012 (US)
Filgrastim Hexal (filgrastim), produced in E. coli, biosimilar to NeupogenHexalNeutropenia2009 (EU)
Biograstim (filgrastim), produced in E. coli, biosimilar to NeupogenABZ-Pharma (Ulm, Germany)Neutropenia2008 (EU)
Withdrawn 2015
Ratiograstim (filgrastim), produced in E. coli, biosimilar to NeupogenRatiopharm (Ulm, Germany)Neutropenia2008 (EU)
Tevagrastim (filgrastim), produced in E. coli, biosimilar to Neupogen. Same product as Granix (see above)Teva (Radebeul, Germany)Neutropenia2008 (EU)
Filgrastim Ratiopharm (filgrastim), produced in E. coli, biosimilar to FilgrastimRatiopharmNeutropenia2008 (EU)
Withdrawn 2011
Neulasta in EU and US, Neupopeg in EU (pegfilgrastim), PEGylated rh G-CSFAmgen (Breda, the Netherlands)Chemotherapy-induced neutropenia2002 (EU & US)
Neupopeg withdrawn 2008 (EU)
Leukine (sargramostim), rh GM-CSF differing from the native protein by an R23L substitution, produced in E. coliSanofi-aventis U.S. (Bridgewater, NJ, USA)Autologous bone marrow transplantation1991 (US)
Withdrawn 2008 and reformulated without EDTA 2008
Neupogen (filgrastim), rh G-CSF differing from native protein by an extra N-terminal methionine, produced in E. coliAmgen (Thousand Oaks, CA, USA)Chemotherapy-induced neutropenia1991 (US)
Other growth factors
Oxervate (cenegermin), rh nerve growth factor, produced in E. coliDompé Farmaceutici (Milan)Neurotophic keratitis2017 (EU)
Increlex (mecaserim), rh IGF-1, produced in E. coliIpsen PharmaGrowth failure in children with IGF-1 deficiency or hGH gene deletion (long-term treatment)2007 (EU)
2005 (US)
iPlex (mecasermin rinfabate), a complex of rh IGF-1 and rh IGF binding protein-3, produced separately in E. coliInsmed (Glen Allen, VA, USA)Growth failure in children with severe primary IGF-1 deficiency or hGH gene deletion (long-term treatment2005 (US)
Withdrawn 2007 for IGF-1 deficiency
Kepivance (palifermin), rh keratinocyte growth factor, produced in E. coliSwedish Orphan BiovitrumSevere oral mucositis in selected patients with hematologic cancers2005 (EU)
2004 (US)
Withdrawn 2016 (EU)
GEM 21S: Regranex (see below) and tricalcium phosphate; growth-factor-enhanced matrixBioMimetic Pharmaceuticals (Franklin, TN, USA)Periodonatally related defects2005 (US)
Regranex (becaplermin), rh platelet-derived growth factor receptor-BB, produced in S. cerevisiaeJohnson & Johnson (Raritan, NJ, USA) Janssen-Cilag International (Beerse, Belgium)Lower extremity diabetic neuropathic ulcers1997 (US)
1999 (EU)
Withdrawn 2012 (EU)
Recombinant interferons, interleukins and tumor necrosis factor
Interferon-α
PEG-Intron/Rebetol combo pack (peginterferon alfa-2b/ribavirin) PEGylated rh IFN-α-2b, produced in E. coli, and ribavirinSchering Plough (Kenilworth, NJ, USA)Chronic hepatitis C2008 (US)
Pegasys (peginterferon alfa-2a), PEGylated IFN-α-2b, produced in E. coliRoche/Genentech (Welwyn Garden City, UK)Hepatitis C2002 (EU & US)
PEG-Intron (peginterferon alfa-2b), PEGylated IFN-α-2b, produced in E. coli.Merck Sharp & DohmeChronic hepatitis C2001 (US)
2000 (EU)
Viraferon (interferon alfa-2b), produced in E. coliSchering Plough (Brussels, Belgium)Chronic hepatitis B, C2000 (EU)
Withdrawn 2008
ViraferonPeg (peginterferon alfa-2b), PEGylated IFN-α-2b, produced in E. coliMerck Sharp & DohmeChronic hepatitis C2000 (EU)
Intron A, Alfatronol (interferon alfa-2b), produced in E. coliMerck Sharp & DohmeCancer, genital warts, hepatitis B and C, HPV2000 (EU)
1986 (US)
Rebetron (ribavirin/interferon alfa-2b), produced in E. coliSchering PloughChronic hepatitis C1999 (US)
Infergen (interferon alficon-1), r IFN-α, synthetic type I, produced in E. coliAstellas Pharma Europe (Leiderdorp, the Netherlands) Kadmon Pharmaceuticals (Warrendale, PA, USA)Chronic hepatitis C1999 (EU)
1997 (US)
Withdrawn 2006 (EU)
Roferon A (interferon alfa-2a), produced in E. coliRocheHairy cell leukemia1986 (US)
Withdrawn 2007
Interferon-β and interferon-γ
Plegridy (peginterferon beta-1a), rh PEGylated IFN- β-1a, produced in CHO cellsBiogen Idec (Maidenhead, UK)Multiple sclerosis2014 (EU & US)
Extavia (interferon beta-1b), rh IFN β-1b, produced in E. coliNovartis Europharm (Camberley, UK) Novartis Pharmaceuticals (East Hanover, NJ, USA)Multiple sclerosis2009 (US)
2008 (EU)
Rebif (interferon beta-1a), rh IFN-β-1a, produced in CHO cellsEMD Serono (London)Relapsing/remitting multiple sclerosis2002 (US)
1998 (EU)
Avonex (interferon beta-1a), rh IFN-β-1a, produced in CHO cellsBiogen Idec (Maidenhead, UK)Relapsing multiple sclerosis1997 (EU)
1996 (US)
Betaferon (interferon beta-1b), r IFN-β-1b differing from native protein by C17S, produced in E. coliBayer PharmaMultiple sclerosis1995 (EU)
Betaseron (interferon beta-β-1b), differing from human protein by C17S, produced in E. coliBerlex Laboratories (Richmond, CA, USA) Chiron (Emeryville, CA, USA)Relapsing/remitting multiple sclerosis1993 (US)
Actimmune (interferon gamma-1b), produced in E. coliVidara Therapeutics (Dublin)Chronic granulomatous disease1990 (US)
Others
Kineret (anakinra), rh IL-1 receptor antagonist, produced in E. coliSwedish Orphan BiovitrumRheumatoid arthritis2001 (US)
Beromun (tasonermin), rh TNF-α, produced in E. coliBoehringer Ingelheim (Ingelheim, Germany)Adjunct to surgery for subsequent tumor removal to prevent or delay amputation1999 (EU)
Neumega (oprelvekin), r IL-11 lacking N-terminal proline of native molecule, produced in E. coliPfizer (Philadelphia), Genetics InstitutePrevention of chemotherapy-induced thrombocytopenia1997 (US)
Proleukin (aldesleukin) r IL-2, differs from native molecule in absence of N-terminal alanine and presence of C125S substitution, produced in E. coliPrometheus Laboratories (San Diego)Renal cell carcinoma1992 (US)
Recombinant vaccines
Hepatitis B
HEPLISAV-B (hepatitis B vaccine (recombinant) adjuvanted), HBsAg, produced in Hansenula polymorpha yeastDynavax Technologies (Berkeley, CA, USA)Prevention of infection caused by all known subtypes of hepatitis B virus2017 (US)
Hexacima, also sold as Hexyon, multi-component vaccine containing r HBsAg, produced in H. polymorpha as one componentSanofi Pasteur (Lyon, France)Immunization against several pathogens and toxins2013 (EU)
Ambirix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSK (Rixensart, Germany)Immunization against hepatitis A and B2002 (EU)
Pediarix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization of children against various conditions inducing hepatitis B2002 (US)
HBVAXPRO (r HBsAg), produced in S. cerevisiaeSanofi PasteurImmunization of children and adolescents against hepatitis B2001 (EU)
Twinrix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization against hepatitis A and B2001 (US)
1997 (EU pediatric form)
1996 (EU adult form)
Infanrix-hexa, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization against diphtheria, tetanus, pertussis, Haemophilus influenzae b, hepatitis B and polio2000 (EU)
Infanrix-penta, combination vaccine, containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization against diphtheria, tetanus, pertussis, polio, and hepatitis B2000 (EU)
Withdrawn 2013
Hepacare (r S, pre-S & pre-S2 HBsAg), produced in a murine cell lineEvans Vaccines (Liverpool, UK)Immunization against hepatitis B2000 (EU)
Withdrawn 2002
Hexavac, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentSanofi PasteurImmunization against diphtheria, tetanus, pertussis, hepatitis B, polio and H. influenzae b2000 (EU)
Withdrawn 2012
Procomvax, combination vaccine containing r HBsAg as one componentSanofi PasteurImmunization against H. influenzae b and hepatitis B1999 (EU)
Withdrawn 2009
Primavax, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentSanofi PasteurImmunization against diphtheria, tetanus and hepatitis B1998 (EU)
Withdrawn 2000
Engerix B, r HBsAg, produced in S. cerevisiaeGSKImmunization against hepatitis B1998 (US)
Infanrix Hep B, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization against diphtheria, tetanus, pertussis and hepatitis B1997 (EU)
Withdrawn 2005
Comvax, combination vaccine containing HBsAg, produced in S. cerevisiae as one componentMerck (Whitehouse Station, NJ, USA)Immunization of infants against H. influenzae b and hepatitis B1996 (US)
Tritanrix-Hep B, combination vaccine containing r HBsAg, produced in S. cerevisiae as one componentGSKImmunization against hepatitis B, diphtheria, tetanus and pertussis1996 (EU)
Withdrawn 2014
Recombivax, r HBsAg, produced in S. cerevisiaeMerck (WhitehouseStation, NJ, USA)Immunization against hepatitis B1986 (US)
Other
Shingrix (zoster vaccine recombinant, adjuvanted), recombinant varicella zoster virus surface glycoprotein E antigen component, produced in CHO cellsGlaxoSmithKline Biologicals (Rixensart, Belgium) GlaxoSmithKline (Research Triangle Park, NC, USA)Prevention of herpes zoster (shingles)2018 (EU) 2017 (US)
Trumenba (meningococcal group B vaccine), two r Neisseria meningitides serogroup B proteins, independently expressed in E. coliPfizer (Philadelphia)Vaccine against N. meningitides serogroup B2017 (EU) 2014 (US)
Pandemic influenza vaccine H5N1, vaccine derived from engineered viral strain containing gene segments from appropriate viral influenza strains, produced in embryonated eggsMedImmune (Nijmegen, the NetherlandsInfluenza vaccine2016 (EU)
Bexsero (meningococcal group B vaccine), mixture of 3 N. meningitidis serogroup B proteins, produced in E. coliNovartis (Cambridge, MA, USA, & Siena, Italy)Active immunization against N. meningitidis serogroup B2015 (US) 2013 (EU)
Gardasil 9, mixture of the major capsid protein (L1) of 9 strains of HPV, each produced in S. cerevisiaeMSD (Lyon, France) Merck (Whitehouse Station, NJ, USA)Active immunization for those above 9 years of age against HPV-caused cancers and genital warts2015 (EU) 2014 (US)
Mosquirix (Plasmodium falciparum and hepatitis B vaccine), virus-like particles comprising the RTS fusion protein of a portion of the circumsporozoite protein from P. falciparum and the N- terminal end of HBsAg, coexpressed in S. cerevisiaeGlaxoSmithKline Biologicals (Rixensart, Belgium)Vaccination against malaria caused by the parasite Plasmodium falciparum2015 (EU); approved for use outside the EU
Flublok, r hemagglutinin proteins from 3 influenza viruses, produced in an insect cell lineProtein Sciences (Meriden, CT, USA)Immunization against influenza2013 (US)
Provenge (sipuleucel-T), autologous peripheral blood mononuclear cells in combination with r prostatic acid phosphatase linked to GM-CSF, produced in an insect cell lineDendreon (London)Prostate cancer2013 (EU)
2010 (US)
Withdrawn 2015 (EU)
Cervarix, r C-terminally truncated major capsid L1 proteins from HPV types 16 and 18, produced in a baculovirus-based expression systemGSKPrevention of cervical cancer2009 (US)
2007 (EU)
Gardasil in EU & US, Silgard in EU, r vaccine containing major capsid proteins from four HPV types, produced in S. cerevisiaeSanofi Pasteur Merck (Whitehouse Station, NJ, USA)Vaccination against diseases caused by HPX2006 (EU & US)
Dukoral (Vibrio cholerae and r cholera toxin B subunit)Valneva Sweden (Stockholm)Immunization against disease caused by V. cholerae subunit O12004 (EU)
Lymerix (r OspA), a lipoprotein found on the surface of B. burgdorferi, produced in E. coliGSKImmunization against Lyme disease1998 (US)
Withdrawn 2002
Triacelluvax, combination vaccine containing r modified pertussis toxin as one componentChiron (Siena, Italy)Immunization against diphtheria, tetanus and pertussis1999 (EU)
Withdrawn 2002
Monoclonal antibody–based products
Aimovig (erenumab-aooe in USA, erenumab in EU), human IgG2 targeting the calcitonin gene-related peptide receptor, produced in CHO cellsAmgen (Thousand Oaks, CA, USA) Novartis (East Hanover, NJ, USA) Novartis Europharm (Dublin)Migraine2018 (EU & US)
Crysvita (burosumab in EU, burosumab-twza in USA), human IgG1 antibody to soluble fibroblast growth factor-23, produced in CHO cellsKyowa Kirin (Galashiels, UK) Ultragenyx Pharmaceutical (Novato, CA, USA)X-linked hypophosphatemia2018 (EU & US)
Fasenra (benralizumab), humanized, afucosylated IgG1 targeting the α subunit of the human IL-5 receptor, produced in CHO cellsAstraZeneca (Södartälje, Sweden, & Wilmington, DE, USA)Asthma2018 (EU) 2017 (US)
Halimatoz (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Hefiya and Hyrimoz (see below)SandozVarious inflammatory conditions mediated by TNF, including rheumatoid arthritis and plaque psoriasis2018 (EU)
Hefiya (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Halimatoz and Hyrimoz (see above and below)SandozVarious inflammatory conditions mediated by TNF, including polyarticular juvenile idiopathic arthritis and plaque psoriasis2018 (EU)
Hemlibra (emicizumab in EU, emicizumab-kxwh in US), humanized, bispecific IgG4 capable of binding factor IXa and factor X, produced in CHO cellsRoche Registration (Welwyn Garden City, UK) Roche/Genentech (South San Francisco, CA, USA)Hemophilia A2018 (EU) 2017 (US)
Herzuma (trastuzumab), r humanized IgG1 against HER2, produced in CHO cells, biosimilar to HerceptinCelltrion Healthcare (Budapest)Breast and gastric cancers2018 (EU)
Hyrimoz (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Halimatoz and Hefiya (see above)SandozVarious inflammatory conditions mediated by TNF, including rheumatoid arthritis and plaque psoriasis2018 (EU)
Ilumya (tildrakizumab-asmn), humanized IgG1 that binds the p19 subunit of IL-23, produced in CHO cellsMerck (Whitehouse Station, NJ, USA)Plaque psoriasis2018 (US)
Kanjinti (trastuzumab), r humanized IgG1 against HER2, produced in CHO cells, biosimilar to HerceptinAmgen Europe (Breda, the Netherlands)Breast and gastric cancers2018 (EU)
Mvasi (bevacizumab in EU, bevacizumab-awwb in US), humanized IgG antibody to human VEGF-A1, produced in CHO cells, biosimilar to AvastinAmgen EuropeAmgen (Thousand Oaks, CA, USA)Various cancers2018 (EU) 2017 (US)
Mylotarg (gemtuzumab ozogamicin), antibody drug conjugate targeting the CD33 surface antigen, consisting of a humanized IgG4 chemically conjugated to N-acetyl-γ-calicheamicin, produced in NS0 mouse myeloma cellsPfizer Europe (Brussels) Pfizer/Wyeth (Philadelphia)Acute myeloid leukemia2018 (EU) 2000 (US) Withdrawn 2010 (US) Reapproved 2017 (US) using modified dosage and regimen
Ocrevus (ocrelizumab), r humanized IgG1 targeting the CD20 surface antigen, produced in CHO cellsRoche Registration Genentech (South San Francisco, CA, USA)Multiple sclerosis2018 (EU) 2017 (US)
Trazimera (trastuzumab), humanized IgG, produced in a CHO cells, biosimilar to HerceptinPfizer (Brussels)Breast cancer, gastric or gastro-esophageal junction adenocarcinoma2018 (EU)
TROGARZO (ibalizumab-uiyk), humanized IgG4 targeting the CD4 domain, produced in NS0 cellsTaiMed Biologics (Irvine, CA, USA) Theratechnologies (Montreal)Human immunodeficiency virus type 1 infection2018 (US)
Zessly (infliximab), chimeric anti-TNF IgG1 produced in CHO cells, biosimilar to Remicade (infliximab)SandozRheumatoid arthritis and selected additional inflammatory diseases2018 (EU)
Amgevita (adalimumab), anti-TNF human IgG1, produced in CHO cells, biosimilar to Humira. Same product as Solymbic and Amjevita (see below)Amgen EuropeRheumatoid arthritis and selected additional inflammatory diseases2017 (EU)
Bavencio (avelumab), human IgG1 specific for programmed death ligand-1 (PD-L1), produced in CHO cellsMerck Europe (Amsterdam) Pfizer (New York)Metastatic Merkel cell carcinoma, urothelial carcinoma2017 (EU & US)
Besponsa (inotuzumab ozogamicin), antibody-drug conjugate consisting of a humanized IgG4 specific for human CD22, produced in CHO cells, covalently linked to the cytotoxic agent N-acetyl-γ-calicheamicin dimethylhydrazidePfizer (Sandwich, UK) Pfizer/Wyeth (Philadelphia)Acute lymphoblastic leukemia2017 (EU & US)
Blitzima (rituximab), chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabTheraSame product as Ritemvia, Truxima and Rituzena (see below)Celltrion Healthcare Hungary (Budapest)Non-Hodgkin lymphoma, CLL, granulomatosis2017 (EU)
Cyltezo (adalimumab in EU, adalimumab-adbm in USA), rh IgG1 against human TNF, produced in CHO cells, biosimilar to HumiraBoehringer Ingelheim (Rhein, Germany) Boehringer Ingelheim (Ridgefield, CT, USA)Range of inflammatory conditions, including psoriasis, rheumatoid arthritis and Crohn's disease2017 (EU & US)
Dinutuximab beta Apeiron (dinutuximab beta), chimeric IgG1 against the disialoganglioside GD2, produced in CHO cells. Same product as Qarziba (see below)Apeiron Biologics (Vienna)Neuroblastoma2017 (EU)
Dupixent (dupilumab), human IgG4 that binds the IL-4α receptor subunit, produced in CHO cellsSanofi-Aventis (Paris & Bridgewater, NJ, USA), Regeneron Pharmaceuticals (Tarrytown, NY, USA)Atopic dermatitis2017 (EU & US)
Imfinzi (durvalumab), human IgG1 blocking the interaction of programmed cell death ligand-1 (PD-L1) with its receptor PD-1 and CD80, produced in CHO cellsAstraZeneca (Wilmington, DE, USA)Urothelial carcinoma2017 (US)
Imraldi (adalimumab), produced in CHO cells, biosimilar to HumiraSamsung Bioepis UK (Chertsey, UK)Rheumatoid arthritis, selected additional inflammatory diseases2017 (EU)
Ixifi (infliximab-qbtx), produced in a mammalian cell line, biosimilar to RemicadePfizer (New York)Various inflammatory conditions, including rheumatoid arthritis, Crohn's disease and psoriasis2017 (US)
Kevzara (sarilumab), human IgG1 that binds IL-6 receptors, produced in CHO cellsSanofi-Aventis (Paris & Bridgewater, NJ, USA), Regeneron Pharmaceuticals (Tarrytown, NY, USA)Rheumatoid arthritis2017 (EU) 2017 (US)
Kyntheum in EU, Siliq in US (brodalumab), human IgG2 against human IL-17 receptor A, produced in CHO cellsLEO Pharma (Ballerup, Denmark) Valeant Pharmaceuticals (Bridgewater, NJ, USA)Psoriasis2017 (EU) 2017 (US)
Ogivri (trastuzumab-dkst), produced in CHO cells, biosimilar to HerceptinMylan (Morgantown, WV, USA, & Zurich)Breast and gastric cancers2017 (US)
Ontruzant, produced in CHO cells, biosimilar to HerceptinSamsung Bioepis UK (Brentford, UK)Breast and gastric cancers2017 (EU)
Qarziba (dinutuximab beta; previously dinutuximab beta EUSA and dinutuximab beta Apeiron), chimeric IgG1 against carbohydrate disialoganglioside GD2, which is overexpressed by cells of neuroectodermal origin such as neuroblastoma cells, produced in CHO cellsEUSA Pharma (Hemel Hempstead, UK)Neuroblastoma2017 (EU)
Renflexis (infliximab-abda), chimeric IgG1 that binds TNF-α, produced in CHO cells, biosimilar to Remicade. Same product as Flixabi (see below)Merck (Kenilworth, NJ, USA)Crohn's disease and various other inflammatory conditions2017 (US)
Ritemvia (rituximab), produced in CHO cells, biosimilar to MabThera. Same product as Blitzima, Rituzena and Truxima (see above and below)Celltrion Healthcare HungaryNon-Hodgkin lymphoma, granulomatosis with polyangiitis, microscopic polyangiitis2017 (EU)
Rituxan Hycela (rituximab and hyaluronidase human), both produced in CHO cellsBiogen (Cambridge, MA, USA), GenentechFollicular lymphoma, diffuse large B-cell lymphoma, CLL2017 (US)
Rituzena (previously Tuxella) (rituximab), produced in CHO cells, biosimilar to MabThera. Same product as Blitzima, Ritemvia and Truxima (see above and below)Celltrion Healthcare HungaryNon-Hodgkin lymphoma, CLL, granulomatosis with polyangiitis2017 (EU)
Rixathon (rituximab), chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabThera. Same product as Riximyo (see below)SandozVarious conditions including non-Hodgkin lymphoma, CLL, rheumatoid arthritis2017 (EU)
Riximyo (rituximab), chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabThera. Same product as Rixathon (see above)SandozVarious conditions including non-Hodgkin lymphoma and rheumatoid arthritis, but excluding CLL2017 (EU)
Solymbic (adalimumab), anti-TNF human IgG1 produced in CHO cells, biosimilar to Humira. Same product as Amgevita and Amjevita (see above and below)Amgen EuropeRheumatoid arthritis and selected additional inflammatory diseases2017 (EU)
Tecentriq (atezolizumab), humanized IgG1 specific for programmed death ligand 1 (PD-L1), engineered to lack Fc glycosylation, produced in CHO cellsRoche Registration (Grenzach-Wyhlen, Germany) Genentech (South San Francisco, CA, USA)Urothelial carcinoma, non-small-cell lung cancer2017 (EU) 2016 (US)
Tremfya (guselkumab), human IgG1 that selectively binds the p19 subunit of IL-23, produced in CHO cellsJanssen-Cilag (Beerse, Belgium) Janssen Biotech (Horsham, PA, USA)Psoriasis2017 (EU & US)
Truxima (rituximab) chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabThera. Same product as Blitzima, Ritemvia, and Truxima (see above)CelltrionSelected cancers and autoimmune disorders2017 (EU)
Zinplava (bezlotoxumab), human IgG directed against Clostridium difficile toxin B, produced in CHO cellsMerck Sharp & DohmeMerck (Whitehouse Station, NJ, USA)C. difficile infection2017 (EU) 2016 (US)
Amjevita (adalimumab-atto), rh IgG1 specific for TNF, produced in CHO cells, biosimilar to Humira. Same product as Solymbic and Amgevita (see above)Amgen (Thousand Oaks, CA, USA)Rheumatoid arthritis and selected additional inflammatory diseases2016 (US)
Anthim (obiltoxaximab), chimeric IgG1 against Bacillus anthracis toxin, produced in NS0 cellsElusys Therapeutics (Pine Brook, NJ, USA)Inhalational anthrax2016 (US)
Cinqair in US, Cinqaero in EU (reslizumab), humanized IgG4 against IL-5, produced in NS0 cellsTeva Respiratory (Frazer, PA USA) Teva (Haarlem, the Netherlands)Asthma2016 (US) 2016 (EU)
Darzalex (daratumumab), human IgG1 against CD-38, produced in CHO cellsJanssen-Cilag Janssen BiotechMultiple myeloma2016 (EU) 2015 (US)
Empliciti (elotuzumab) humanized IgG1 against the cell surface receptor SLAMF7, produced in NS0 cellsBristol-Myers Squibb (Uxbridge, UK, & Princeton, NJ, USA)Multiple myeloma (in combination with lenalidomide and dexamethasone)2016 (EU) 2015 (US)
Flixabi (infliximab), chimeric IgG1 against TNF-α, produced in CHO cells, biosimilar to Remicade. Same product as Renflexis (see above)Samsung Bioepis (Chertsey, UK)Various forms of arthritis, psoriasis, colitis, Crohn's disease, ankylosing spondylitis2016 (EU)
Inflectra in EU and US, Remsima in EU (infliximab in EU, infliximab-dyyb in US), chimeric IgG1 specific for TNF-α, produced in murine Sp2/0 cells, biosimilar to RemicadeInflectra: Hospira (Lake Forest, IL, USA), Celltrion (Incheon, Republic of Korea) and Hospira (Royal Leamington Spa, UK); Remsima: Celltrion (Budapest)Certain forms of arthritis and psoriasis, Crohn's disease, ulcerative colitis, ankylosing spondylitis2016 (US) 2013 (EU)
Lartruvo (olaratumab), rh IgG1 specific for human platelet-derived growth factor receptor-α, produced in NS0 cellsEli Lilly (Utrecht, the Netherlands, & Indianapolis)Sarcoma2016 (EU & US)
Portrazza (necitumumab), human IgG1 against the ligand binding site of human EGF receptor, produced in NS0 cellsEli Lilly (Utrecht, the Netherlands, & Indianapolis)Non-small-cell lung cancer (in combination with gemcitabine and cisplatin)2016 (EU) 2015 (US)
Taltz (ixekizumab), humanized IgG4 against hIL-17A, produced in CHO cellsEli Lilly (Utrecht, the Netherlands, & Indianapolis)Psoriasis2016 (EU & US)
Zinbryta (daclizumab), humanized IgG1 against IL-2Rα, produced in NS0 cellsBiogen (Cambridge, MA US) Biogen Idec (Maidenhead, UK)Multiple sclerosis2016 (EU & US) Withdrawn 2018 (EU & US)
Blincyto (blinatumomab), bispecific T-cell engager antibody construct (BiTE), produced in CHO cellsAmgen Europe Amgen (Thousand Oaks, CA, USA)Acute lymphoblastic leukemia2015 (EU) 2014 (US)
Cosentyx (secukinumab), human IgG1 selectively binding human IL-17a, produced in CHO cellsNovartis Europharm (Camberley, UK) Novartis (East Hanover, NJ, USA)Moderate to severe plaque psoriasis in adults2015 (EU & US)
Keytruda (pembrolizumab), humanized IgG4 capable of binding to the receptor PD-1, produced in CHO cellsMerck Sharp & Dohme Merck (Whitehouse Station, NJ, USA)Advanced (unresectable or metastatic) melanoma in adults2015 (EU) 2014 (US)
Nivolumab BMS (nivolumab), human IgG4 against the receptor PD-1, produced in CHO cells. Same product as Opdivo (see below)Bristol-Myers Squibb (Uxbridge, UK)Locally advanced or metastatic squamous non-small-cell lung cancer after prior chemotherapy in adultsJuly 2015 (EU) Withdrawn November 2015
Nucala (mepolizumab), humanized IgG1 capable of binding human IL-5, produced in CHO cellsGlaxoSmithKline (Cork, Ireland) GSK (Research Triangle Park, NC, USA)Add-on treatment for severe refractory eosinophilic asthma in adult patients2015 (EU & US)
Opdivo (nivolumab), human IgG4 against the receptor PD-1, produced in CHO cells. Same product as nivolumab BMS (see above)Bristol-Myers Squibb (Uxbridge, UK, & Princeton, NJ, USA)Melanoma (as monotherapy or in combination with ipilimumab), non-small-cell lung cancer, renal cell carcinoma2015 (EU) 2014 (US)
Praluent (alirocumab), human IgG1 targeting PCSK9, produced in CHO cellsSanofi-Aventis (Paris & Bridgewater, NJ, USA) Regeneron Pharmaceuticals (Tarrytown, NY, USA)Primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet2015 (EU & US)
Praxbind (idarucizumab), humanized IgG1 Fab fragment capable of binding the anticoagulant drug dabigatran, produced in CHO cellsBoehringer Ingelheim (Rhein, Germany, & Ridgefield, CT, USA)Rapid reversal agent for the anticoagulant drug dabigatran2015 (EU & US)
Repatha (evolocumab), human IgG2 capable of binding human PCSK-9, produced in CHO cellsAmgen Europe Amgen (Thousand Oaks, CA, USA)Hypercholesterolemia and mixed dyslipidemia2015 (EU & US)
Unituxin (dinutuximab), chimeric IgG1 targeting human disialoganglioside (GD2), produced in Sp2/0 cellsUnited Therapeutics (Chertsey, UK, & Silver Spring, MD, USA)Neuroblastoma (administered in combination with GM-CSF, IL-2 and isotretinoin)2015 (EU & US) Withdrawn 2017 (EU)
Cyramza (ramucirumab), human mAb that binds the VEGF-2 receptor, produced in NS0 cellsEli Lilly Nederland (Utrecht, the Netherlands) Eli Lilly (Indianapolis)Gastric cancer2014 (EU & US)
Entyvio (vedolizumab), humanized IgG targeting the human α4β7 integrin, produced in CHO cellsTakeda Pharmaceuticals (Deerfield, IL, USA) Takeda Pharma (Taastrup, Denmark)Ulcerative colitis, Crohn's disease2014 (EU & US)
Gazyva in US, Gazyvaro in EU (obinutuzumab), humanized, glycoengineered mAb specific for B-cell antigen CD20, produced in CHO cellsRoche/GenentechRoche (Welwyn Garden City, UK)CLL2014 (EU) 2013 (US)
Sylvant (siltuximab), chimeric mAb that binds human IL-6, produced in CHO cellsJanssen BiotechMulticentric Castleman disease2014 (EU & US)
Kadcyla (trastuzumab emtansine), humanized mAb specific for HER2 antigen, produced in CHO cells and conjugated to the small molecule cytotoxin DM1Roche (Welwyn Garden City, UK)Breast cancer2013 (EU & US)
Simponi Aria (golimumab). Active substance same as that in Simponi (see below); different strength and mode of administrationJanssen BiotechRheumatoid arthritis2013 (US)
Perjeta (pertuzumab), human mAb specific for HER2, produced in CHO cellsRoche/GenentechBreast cancer2013 (EU)
2012 (US)
Abthrax (raxibacumab), human IgG mAb against the protective antigen (PA) of B. anthracis, produced in NS0 cellsGSK/Human Genome Sciences (Rockville, MD, USA)Inhalational anthrax2012 (US)
Adcetris (brentuximab vedotin), chimeric mAb conjugate specific for human CD30 (expressed on the surface of lymphoma cells), produced in CHO cellsTakeda Pharma (Roskilde, Denmark)
Seattle Genetics
Lymphoma2012 (EU)
2011 (US)
Benlysta (belimumab), human mAb that targets human B-lymphocyte stimulator (BLyS), a B cell survival factor. produced in NS0 cellsHuman Genome Sciences Glaxo Group (Greenford, UK)Lupus2011 (EU & US)
Xgeva (denosumab) (see Prolia)Amgen EuropeBone loss associated with cancer2011 (EU)
2010 (US)
Yervoy (ipilimumab), human mAb binding to CTLA-4 (a negative regulator of T-cell activation), thereby enhancing T cell activation and proliferation, produced in CHO cellsBristol-Myers Squibb (Uxbridge, UK)Melanoma2011 (EU & US)
Actemra in US, RoActemra in EU (tocilizumab), humanized mAb specific for IL-6, produced in a mammalian cell lineRoche (Welwyn Garden City, UK)Rheumatoid arthritis2010 (US)
2009 (EU)
Arzerra (ofatumumab), human mAb specific for CD20, produced in NS0 hybridoma cellsNovartis (East Hanover, NJ, USA), Genmab (Greenford, UK)CLL2010 (EU)
2009 (US)
Prolia (denosumab), human mAb specific for receptor activator of nuclear factor κB ligand (RANKL), produced in CHO cellsAmgen EuropeOsteoporosis in postmenopausal women2010 (EU & US)
Scintimun (besilesomab), murine mAb against nonspecific cross-reacting antigen-95 (found on surface of granulocytes), produced in hybridoma cellsCIS Bio International (Gif-sur-Yvette, France)In vivo diagnosis or investigation of sites of inflammation or infection via scintigraphic imaging2010 (EU)
Cimzia (certolizumab pegol), anti-TNF-α humanized and PEGylated antibody Fab fragment, produced in E. coliUCB Pharma (Brussels, Belgium)Crohn's disease, rheumatoid arthritis2009 (EU)
2008 (US)
Ilaris (canakinumab), human mAb specific for IL-1β, produced in Sp2/0 cellsNovartis Pharmaceuticals (East Hanover, NJ, USA) Novartis Europharm (Dublin)Cryopyrin-associated periodic syndromes (CAPS)2009 (EU & US)
Removab (catumaxomab), bispecific engineered antibody targeting the human epithelial cell adhesion molecule and human CD3 expressed on T-lymphocytes, produced in hybridoma cellsNeovii Biotech (Gräfelfing, Germany)Malignant ascites in patients with carcinomas expressing epithelial cell adhesion molecule2009 (EU)
Withdrawn 2017
Simponi (golimumab), human mAb specific for TNF-α, produced in Sp2/0 cellsJanssen Biologics (Leiden, the Netherlands) Janssen Biotech (Horsham, PA, USA)Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis2009 (EU & US)
Stelara (ustekinumab), human MAb specific for the p40 subunit of IL-12 and IL-23, produced in Sp2/0 cellsJanssen-CilagModerate to severe plaque psoriasis2009 (EU & US)
Lucentis (ranibizumab), humanized IgG fragment that binds and inactivates VEGF-A, produced in E. coliRoche/GenentechNeovascular (wet) age-related macular degeneration2007 (EU)
2006 (US)
Soliris (eculizumab), humanized IgG that binds human C5 complement protein, produced in a murine myeloma cell lineAlexion Pharmaceuticals (Cheshire, CT, USA, & Paris)Paroxysmal nocturnal hemoglobinuria2007 (EU & US)
Vectibix (panitumumab), human mAb that binds to human EGF receptor, produced in CHO cellsAmgen Europe AbgenixEGF receptor–expressing colorectal carcinoma2007 (EU)
2006 (US)
Tysabri (natalizumab), humanized mAb against selected leukocyte integrins, produced in murine myeloma cellsBiogen Inc. (Cambridge, MA, USA) Biogen Netherlands (Badhoevedorp, the Netherlands)Relapsing forms of multiple sclerosis2006 (EU)
2004 (US)
Suspended 2005 (US)
Resumed 2006 (US)
Xolair (omalizumab), humanized mAb that binds IgE at the site of high-affinity IgE receptor binding, produced in CHO cellsRoche/GenentechModerate to severe persistent asthma in adults and adolescents2005 (EU)
2003 (US)
Zevalin (ibritumomab tiuxetan), murine mAb against the CD20 antigen, produced in CHO cellsSpectrum Pharmaceuticals (Amsterdam)Non-Hodgkin lymphoma2004 (EU)
2002 (US)
Erbitux (cetuximab), chimeric mAb against human EGF receptor, produced in Sp2/0 cellsMerck KGaA (Darmstadt, Germany) Eli Lilly (Indianapolis)EGF receptor–expressing metastatic colorectal cancer2004 (EU & US)
Raptiva (efalizumab), humanized mAb that binds to LFA-1, which is expressed on all leukocytes; produced in CHO cellsSerono (London, UK) GenentechChronic moderate to severe plaque psoriasis in adults2004 (EU)
2003 (US)
Withdrawn 2009
Avastin (bevacizumab), humanized mAb against VEGF, produced in CHO cellsRoche/Genentech (Welwyn Garden City, UK)Metastatic colorectal cancer, glioblastoma, metastatic renal carcinoma2005 (EU)
2004 (US)
NeutroSpec (fanolesomab), murine mAb against CD15, a surface antigen of selected leukocytes, produced in hybridoma cellsPalatin Technologies (Cranbury, NJ, USA), Mallinckrodt Pharmaceuticals (Hazelwood, MO, USA)Imaging of equivocal appendicitis2004 (US)
Withdrawn 2005
Humira in EU & US, Trudexa in EU (adalimumab), anti-TNF human mAb, produced in CHO cellsAbbVie (Maidenhead, UK)Rheumatoid arthritis2003 (EU)
2002 (US)
Trudexa withdrawn 2007 (EU)
Bexxar (tositumomab), radiolabeled mAb against CD20, produced in murine hybridoma cellsGSKCD20-positive follicular non-Hodgkin lymphoma2003 (US)
Withdrawn 2014
Mabcampath (EU) or Campath (US) (alemtuzumab), humanized mAb against CD52, a surface antigen of B lymphocytes, produced in CHO cellsGenzyme (Naarden, the Netherlands) Millennium (Cambridge, MA, USA)CLL2001 (EU & US)
Withdrawn (EU) 2012
Herceptin (trastuzumab), humanized mAb against HER2, produced in a murine cell lineRoche (Welwyn Garden City, UK)Treatment of metastatic breast cancer overexpressing HER2 protein2000 (EU)
1998 (US)
Remicade (infliximab), chimeric mAb against TNF-α, produced in Sp2/0 cellsJanssen (Leiden, the Netherlands)Crohn's disease1999 (EU)
1998 (US)
Synagis (palivizumab) humanized mAb directed against an epitope on the surface of respiratory syncytial virus, produced in a murine myeloma cell lineMedImmune (Gaithersburg, MD, USA) AbbVie Deutschland (Ludwigshafen, Germany)Prophylaxis of lower respiratory tract disease caused by syncytial virus in children1999 (EU)
1998 (US)
Zenapax (daclizumab), humanized mAb against the IL-2 receptor α-chain, produced in NS0 cellsRoche (Welwyn Garden City, UK) Biogen (Cambridge, MA, USA)Prevention of acute kidney transplant rejection1999 (EU)
1997 (US)
Withdrawn 2009 (EU)
Humaspect (votumumab), human mAb against cytokeratin tumor-associated antigen, produced in a human lymphoblastoid cell lineKS Biomedix (Farnham, UK)Detection of carcinoma of the colon or rectum1998 (EU)
Withdrawn 2004
MabThera in EU, Rituxan in US (rituximab), chimeric mAb against CD20 surface antigen of B lymphocytes, produced in CHO cellsRoche (Welwyn Garden City, UK)Non-Hodgkin lymphoma1998 (EU)
1997 (US)
Simulect (basiliximab), chimeric mAb directed against the α-chain of the IL-2 receptor, produced in a murine myeloma cell lineNovartis (Horsham, UK)Prophylaxis of acute organ rejection in allogeneic renal transplantation1998 (EU)
LeukoScan (sulesomab), murine mAb Fab fragment against granulocyte surface nonspecific cross-reacting antigen-90, produced in Sp2/0 cellsImmunomedics (Darmstadt, Germany)Diagnostic imaging for infection and inflammation in bone of patients with osteomyelitis1997 (EU)
Withdrawn 2018
Verluma (nofetumomab), murine mAb Fab fragment directed against carcinoma-associated antigen, produced in a murine cell lineBoehringer Ingelheim, NeoRx (Seattle)Detection of small-cell lung cancer1996 (US)
Withdrawn 1999
Tecnemab KI (antimelanoma Mab fragments), murine mAb fragments (Fab/Fab2 mix) against HMW-MAA, produced in murine ascites cultureAmersham Sorin (Milan)Diagnosis of cutaneous melanoma lesions1996 (EU)
Withdrawn 2000
ProstaScint (capromab pentetate), murine mAb against the tumor surface antigen PSMA, produced in a murine cell lineEUSA Pharma USA (Langhorne, PA, USA)Detection, staging and follow-up of prostate adenocarcinoma1996 (US)
MyoScint (imiciromab pentetate), murine mAb fragment directed against human cardiac myosin, produced in a murine cell lineCentocorMyocardial infarction imaging1996 (US)
Withdrawn 1999
CEA-scan (arcitumomab), murine mAb Fab fragment against human carcinoembryonic antigen (CEA), produced in mouse ascitesImmunomedicsDetection of recurrent or metastatic colorectal cancer1996 (EU & US)
Withdrawn 2005 (EU & US)
Indimacis 125 (igovomab), murine mAb Fab2 fragment against the tumor-associated antigen CA125, produced in a murine cell lineCIS Bio (Gif-sur-Yvette, France)Diagnosis of ovarian adenocarcinoma1996 (EU)
Withdrawn 2009
ReoPro (abciximab), Fab fragments derived from a chimeric mAb against the platelet surface receptor GPIIb/III, produced in a mammalian cell lineJanssen Biologics (Leiden, the Netherlands), CentocorPrevention of blood clots1994 (US)
OncoScint CR/OV (satumomab pendetide), murine mAb against the tumor-associated glycoprotein TAG-72, produced in a murine cell lineCytogen (Princeton, NJ, USA)Detection, staging and follow-up of colorectal and ovarian cancers1992 (US)
Withdrawn 2002
Orthoclone OKT3 (muromomab CD3), murine mAb against the T-lymphocyte surface antigen CD3, produced in a murine cell lineCentocor Ortho Biotech Products (Raritan, NJ, USA)Reversal of acute kidney transplant rejection1986 (US)
Other recombinant products
Bone morphogenetic proteins
Opgenra (eptotermin alfa), rh BMP-7, produced in CHO cellsOlympus Biotech (Limerick, Ireland)Posterolateral lumbar spinal fusion2009 (EU)
Withdrawn 2016
Infuse bone graft, containing dibotermin alfa, a rh BMP-2 produced in CHO cells, placed on an absorbable collagen sponge. Active substance same as that in Infuse (see below)Wyeth (Madison, NJ, USA)Acute open tibial shaft fracture2004 (US)
Inductos (dibotermin alfa), rh BMP-2, produced in CHO cellsMedtronic BioPharma (Heerlen, the Netherlands) Wyeth EuropaGenetics InstituteAcute tibia fractures2002 (EU)
Infuse (rh BMP2), produced in CHO cellsMedtronic Sofamor Danek (Memphis, TN, USA)Promotes fusion of lower spine vertebrae2002 (US)
OP-1 implant in US, Osigraft in EU (eptotermin alfa), rh BMP-7, produced in CHO cellsOlympus Biotech (Limerick, Ireland) Stryker Biotech (Hopkinton, MA, USA)Non-union of tibia2001 (EU & US)
Withdrawn 2015 (EU)
Recombinant enzymes
Palynziq (pegvaliase-pqpz), r phenylalanine ammonia lyase, produced in E. coli and PEGylatedBioMarin (Novato, CA, USA)Phenylketonuria2018 (US)
Lamzede (velmanase alfa), rh α-mannosidase, expressed in precursor form in CHO cellsChiesi Farmaceutici (Parma, Italyα-mannosidosis2018 (EU)
Brineura (cerliponase alfa), rh serine tripeptidyl peptidase-1, expresses in proenzyme form in CHO cellsBioMarin (Cork, Ireland), BioMarinCLN2 disease (tripeptidyl peptidase-1 deficiency)2017 (EU & US)
Mepsevii (vestronidase alfa-vjbk), r human lysosomal β-glucuronidase, produced in CHO cellsUltragenyx Pharmaceutical (Novato, CA, USA)Mucopolysaccharidosis VII2017 (US)
Oncaspar (pegaspargase), r asparaginase, produced in E. coli and conjugated to monomethoxypropylene glycolBaxalta InnovationsLymphoblastic leukemia, lymphoma2016 (EU)
Spectrila (asparaginase), r asparaginase, produced in E. coliMedac Gesellschaft für klinische Spezialpräparate (Wedel, Germany)Lymphoblastic leukemia, lymphoma2016 (EU)
Kanuma (sebelipase alfa), rh lysosomal acid lipase, produced in the eggs of transgenic chickensAlexion Europe (Rueil-Malmaison, France) Alexion Pharmaceuticals (Cheshire, CT, USA)Enzyme replacement therapy in patients with lysosomal acid lipase deficiency2015 (EU & US)
Strensiq (asfotase alfa), dimeric fusion protein containing a soluble catalytic domain of human tissue nonspecific alkaline phosphatase linked to an IgG Fc domain and a deca-aspartate peptide domain, produced in CHO cellsAlexion Europe (Rueil-Malmaison, France) Alexion (Cheshire, CT, USA)Enzyme replacement therapy in patients with pediatric-onset hypophosphatasia2015 (EU & US)
Vimizim (elosulfase alfa), rh N-acetlygalactosamine-6-sulfatase, produced in CHO cellsBioMarin (London, UK)Mucopolysaccharidosis IVA (Morquio A syndrome)2014 (EU & US)
Krystexxal (pegloticase), r urate oxidase, PEGylated after synthesis, produced in E. coliSavient Pharma Ireland (Dublin) Crealta Pharmaceuticals (Lake Forest, IL, USA)Gout2013 (EU)
2010 (US)
Withdrawn 2016 (EU)
Elelyso (taliglucerase alfa), rh glucocerebrosidase, produced in engineered carrot root cell culturePfizer (New York), Protalix BioTherapeutics (Karmiel, Israel)Gaucher disease2012 (US)
Voraxaze (glucarpidase), r carboxypeptidase, produced in E. coliBTG International (West Conshohocken, PA, USA)Toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function2012 (US)
Lumizyme (alglucosidase alfa), rh acid-α-glucosidase, produced in CHO cellsSanofi GenzymePompe disease (glycogen storage disease type II)2010 (US)
VPRIV (velaglucerase alfa), rh glucocerebrosidase, produced in a human fibroblast cell lineShire Human Genetic Therapies (Danderyd, Sweden)Gaucher disease2010 (EU & US)
Elaprase (idursulfase), rh iduronate-2-sulfatase, produced in a human cell lineShire Human Genetic TherapiesMucopolysaccharidosis II (Hunter syndrome)2007 (EU)
2006 (US)
Naglazyme (galsulfase), rh N-acetylgalactosamine-4-sulfatase, produced in CHO cellsBioMarin (London & Novato, CA, USA)Long-term enzyme replacement therapy in mucopolysaccharidosis VI2006 (EU)
2005 (US)
Myozyme (algulcosidase alfa), rh acid glucosidase, produced in CHO cellsSanofi Genzyme (Naarden, the Netherlands)Pompe disease2006 (EU & US)
Aldurazyme (laronidase), r α-l-iduronidase, produced in CHO cellsBioMarinLong-term replacement in mucopolysaccharidosis I2003 (EU & US)
Hylenex (hyaluronidase), rh hyaluronidase, produced in CHO cellsHalozyme Therapeutics (San Diego)Adjuvant to increase absorption and dispersion of other drugs2005 (US)
Fabrazyme (agalsidase beta), rh α-galactosidase, produced in CHO cellsSanofi Genzyme (Naarden, the Netherlands)Fabry disease (α-galactosidase A deficiency)2003 (US)
2001 (EU)
Replagal (agalsidase alfa), rh α-galactosidase, produced in a human cell lineShire Human Genetic Therapies, TKT EuropeFabry disease (α-galactosidase A deficiency)2001 (EU)
Fasturtec in EU, Elitex in US (rasburicase), r urate oxidase, produced in S. cerevisiaeSanofi (Paris)Hyperuricemia2002 (US)
2001 (EU)
Cerezyme (imiglucerase), rh β-glucocerebrosidase, produced in CHO cellsGenzyme (Naarden, the Netherlands)Gaucher disease1997 (EU)
1994 (US)
Pulmozyme (dornase alpha), r DNase, produced in CHO cellsRoche/GenentechCystic fibrosis1993 (US)
Fusion proteins
Erelzi (etanercept in EU, etanercept-szzs in USA), r dimeric fusion protein consisting of TNF receptor extracellular domains linked to an IgG1 Fc region, produced in CHO cells, biosimilar to EnbrelSandoz (Kundl, Austria, & Princeton, NJ, USA)Rheumatoid arthritis, selected other inflammatory diseases2017 (EU) 2016 (US)
Lifmior (etanercept), r dimeric fusion protein consisting of TNF receptor extracellular domains linked to an IgG1 Fc region, produced in CHO cells. Same product as Enbrel (see below)Pfizer Europe (Brussels)Rheumatoid arthritis, selected other inflammatory diseases2017 (EU)
Benepali (etanercept), rh TNF receptor–IgG Fc fusion protein, produced in CHO cells, biosimilar to EnbrelSamsung Bioepis (Chertsey, UK)Arthritis, psoriasis, axial spondyloarthritis2016 (EU)
Zaltrap (aflibercept), combination drug consisting of binding domains of VEGF receptors 1 and 2 fused to an IgG Fc, produced in CHO cells. Same active substance as in Eylea (see below)Sanofi (Paris) Sanofi-aventis US (Bridgewater, NJ, USA)Metastatic colorectal cancer2013 (EU)
2012 (US)
Eylea (aflibercept), fusion protein consisting of extracellular ligand binding domains of VEGF receptor fused to IgG Fc, produced in CHO cells). Same active substance as in Zaltrap (see above)Bayer (Berlin) Regeneron Pharmaceuticals (Tarrytown, NY)Neovascular (wet) age-related macular degeneration2012 (EU)
2011 (US)
Nulojix (belatacept), fusion protein consisting of the extracellular domain of human CTLA4 fused to IgG Fc; binds CD80 and CD86 on antigen-presenting cells, thereby inhibiting T cell activation, produced in CHO cellsBristol-Myers Squibb (Uxbridge, UK)Prophylaxis of organ rejection following kidney transplant2011 (EU & US)
Arcalyst in US, Rilonacept Regeneron in EU (rilonacept), dimeric fusion protein with each monomer consisting of the ligand-binding domains of the human IL-1 receptor and the IL-1 receptor accessory protein along with the Fc region of human IgG-1, produced in CHO cellsRegeneron Pharmaceuticals (London, UK, & Tarrytown, NY, USA)Cryopyrin-associated periodic syndromes (CAPS)2009 (EU)
2008 (US)
Withdrawn 2012 (EU)
Nplate (romiplostim), dimeric fusion protein with each monomer consisting of two thrombopoietin receptor binding domains and the Fc region of human IgG-1, produced in E. coliAmgen EuropeThrombocytopenia2009 (EU)
2008 (US)
Orencia (abatacept), fusion protein that links the extracellular domain of human cytotoxic T-lymphocyte associated antigen-4 with modified Fc region of IgG1, produced in a mammalian cell lineBristol-Myers Squibb (Uxbridge, UK)Rheumatoid arthritis2007 (EU)
2005 (US)
Amevive (alefacept), dimeric fusion protein consisting of the extracellular CD2-binding portion of human LFA-3 linked to the Fc region of human IgG1, produced in CHO cellsAstellas Pharma (Deerfield, IL, USA)Moderate to severe chronic plaque psoriasis in adults2003 (US)
Withdrawn 2011
Enbrel (etanercept), r TNF receptor–IgG fragment fusion protein, produced in CHO cells. Same product as Lifmior (see above)Amgen (Thousand Oaks, CA, USA) Pfizer (Sandwich, UK)Rheumatoid arthritis2000 (EU)
1998 (US)
Ontak (denileukin diftitox), r IL-2–diphtheria toxin fusion protein that targets cells displaying a surface IL-2 receptor, produced in E. coliEisai (Tokyo), Ligand Pharmaceuticals (San Diego)Cutaneous T-cell lymphoma1999 (US)
Gene therapy and nucleic acid–based
Tegsedi (inotersen), a 20-nucleotide single-stranded oligonucleotide manufactured by direct chemical synthesisIonis USA (London)Hereditary transthyretin amyloidosis2018 (EU)
Luxturna (voretigene neparvovec-rzyl), a live, nonreplicating adeno-associated virus genetically modified to express the human RPE65 geneSpark Therapeutics (Philadelphia)Retinal dystrophy2017 (US)
Spinraza (nusinersen sodium), an 18-nucleotide antisense oligonucleotide manufactured by direct chemical synthesisBiogen Idec (Maidenhead, UK) Biogen (Cambridge, MA, USA)Spinal muscular atrophy2017 (EU) 2016 (US)
Exondys 51 (eteplirsen), a chemically synthesized antisense oligonucleotideSarepta Therapeutics (Cambridge, MA, USA)Duchenne muscular dystrophy2016 (US)
Imlygic (talimogene laherparepvec), an engineered herpes simplex virus type 1 capable of producing GM-CSFAmgen EuropeAmgenMelanoma2015 (EU & US)
Kynamro (mipomersen sodium), a chemically synthesized antisense oligonucleotideKastle Therapeutics (Chicago)Familial hypercholesterolemia2013 (US)
Glybera (alipogene tiparvovec), human LPL gene housed in an engineered AAV1 vectoruniQure (Amsterdam)Lipoprotein lipase deficiency2012 (EU)
Withdrawn 2017
Macugen (pegaptanib sodium injection), a synthetic PEGylated oligonucleotide that specifically binds VEGFPfizer, PharmaSwiss Ceska Republika (Prague) Eyetech (Palm Beach Gardens, FL, USA),Neovascular, age-related macular degeneration2006 (EU)
2004 (US)
Vitravene (fomivirsen), an antisense oligonucleotideNovartis Ophthalmics Europe (Farnborough, UK) Isis Pharmaceuticals (Carlsbad, California)Cytomegalovirus retinitis in AIDS patients1999 (EU)
1998 (US)
Withdrawn 2002 (EU)
Engineered cell–based
Kymriah (tisagenlecleucel), autologous T cells genetically modified to encode an anti-CD19 chimeric antigen receptor comprising a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB (CD137) and CD3ζNovartis (East Hanover, NJ, USA)Acute lymphoblastic leukemia, large B-cell lymphoma2017 (US)
Yescarta (axicabtagene ciloleucel), autologous T cells genetically modified to express a chimeric antigen receptor comprising a murine anti-CD19 single-chain variable fragment (scFv) linked to CD28 and CD3ζ co-stimulatory domainsKite Pharma (Santa Monica, CA, USA)Large B-cell lymphoma2017 (US)
Strimvelis, autologous CD34+ cells transduced with an engineered retroviral vector encoding the human adenosine deaminase sequenceGlaxoSmithKline (Cork, Ireland)Severe combined immunodeficiency2016 (EU)
Zalmoxis, allogeneic T cells genetically modified to express the herpes simplex thymidine kinase suicide gene and a truncated form of the human low-affinity nerve growth factor receptor geneMolMed (Milan)Hematopoietic stem cell transplantation, graft-versus-host disease2016 (EU)
Data were collected from several sources (http://www.fda.gov/, https://www.ema.europa.eu/en). r, recombinant; rh, recombinant human; CHO, Chinese hamster ovary cell line; HEK, human embryo kidney cell line; BHK, baby hamster kidney cell line; PEG, polyethylene glycol; mAb, monoclonal antibody; tPA, tissue plasminogen activator; hGH, human growth hormone; FSH, follicle stimulating hormone; EPO, erythropoietin; IGF, insulin-like growth factor; BMP, bone morphogenetic protein; EGF, epidermal growth factor; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor; VEGF, vascular endothelial growth factor; IFN, interferon; IL, interleukin; HPV, human papillomavirus; HBsAg, hepatitis B surface antigen; TNF, tumor necrosis factor; GLP, glucagon-like peptide; HER2, human epidermal growth factor receptor 2, CLL, chronic lymphocytic leukemia.