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

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 A

2018 (EU)

Afstyla (lonoctocog alfa), B-domain-truncated rh coagulation factor VIII, produced in CHO cells

CSL Behring (Marburg, Germany, & Kankakee, IL, USA)

Hemophilia A

2017 (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 A

2017 (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 A

2016 (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 A

2016 (EU & US)

Vonvendi (von Willebrand factor (recombinant)), produced in CHO cells

Baxalta (Westlake Village, CA, USA)

von Willebrand disease

2015 (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) Octapharma

Hemophilia A

2015 (US) 2014 (EU)

Obizur (susoctocog alfa), r B-domain-deleted porcine factor VIII, produced in BHK cells

Baxalta Innovations Baxter Healthcare (Westlake Village, CA, USA)

Acquired hemophilia due to development of autoantibodies against factor VIII

2015 (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)

Baxalta

Hemophilia A

2015 (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 cells

Swedish Orphan Biovitrum (Stockholm) Biogen Idec (Cambridge, MA, USA)

Hemophilia A

2015 (EU) 2014 (US)

NovoEight (turoctocog alfa), rh factor VIII analog that, when activated, is structurally comparable to endogenous human factor VIIIa, produced in CHO cells

Novo Nordisk (Bagsvaerd, Denmark, & Plainsboro, NJ, USA)

Hemophilia A

2013 (EU & US)

Xyntha (antihemophilic factor), rh coagulation factor VIII, produced in CHO cells

Pfizer/Wyeth (Philadelphia)

Hemophilia A

2008 (US)

Advate (octocog alfa), rh factor VIII, produced in CHO cells

Baxter Healthcare (Vienna & Deerfield, IL, USA)

Hemophilia A

2004 (EU)

2003 (US)

Helixate NexGen (octocog alfa), rh factor VIII, produced in BHK cells

Bayer (Berlin)

Hemophilia A

2000 (EU)

ReFacto (moroctocog alfa), B-domain-deleted rh factor VIII, produced in CHO cells

Pfizer/Wyeth (Sandwich, UK) Genetics Institute (Cambridge, MA, USA)

Hemophilia A

2000 (US)

1999 (EU)

Kogenate, Helixate (antihemophilic factor), rh factor VIII, produced in BHK cells. Sold as Helixate by Aventis Behring through a license agreement

Bayer (Leverkusen, Germany, & Berkeley, CA, USA)

Hemophilia A

2000 (EU)

1993 (US)

Bioclate (antihemophilic factor), rh factor VIII, produced in CHO cells

Aventis Behring (King of Prussia, PA, USA)

Hemophilia A

1993 (US)

Recombinate (antihemophilic factor), rh factor VIII, produced in CHO cells

Baxter Healthcare (Deerfield, IL, USA), Genetics Institute

Hemophilia A

1992 (US)

Andexxa (coagulation factor Xa recombinant inactivated-zhzo), r modified human factor Xa, produced in CHO cells

Portola 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 bleeding

2018 (US)

Rebinyn (rh coagulation factor IX) in US, Refixia (nonacog beta pegol) in EU: rh coagulation factor IX, produced in CHO cells and PEGylated

Novo Nordisk

Hemophilia B

2017 (EU & US)

Alprolix (eftrenonacog alfa), rh coagulation factor IX fused to a human IgG1 Fc domain, produced in HEK cells

Biogen Idec (Maidenhead, UK, & Cambridge, MA, USA)

Hemophilia B

2016 (EU) 2014 (US)

Idelvion (albutrepenonacog alfa), rh factor IX–albumin fusion protein, produced in CHO cells

CSL Behring

Hemophilia B

2016 (EU & US)

Ixinity (coagulation factor IX (recombinant)), rh coagulation factor IX, produced in CHO cells

Aptevo BioTherapeutics (Berwyn, PA, USA)

Hemophilia B

2015 (US)

Rixubis (nonacog gamma), rh factor IX, produced in CHO cells

Baxalta Innovations (Vienna) Baxter Healthcare (Westlake Village, CA, USA)

Hemophilia B

2014 (EU) 2013 (US)

Tretten in US, Novothirteen in EU (catridecog), rh factor XIII A-subunit, produced in S. cerevisiae

Novo Nordisk

Congenital factor XIII A-subunit deficiency

2013 (US)

2012 (EU)

Recothrom (thrombin), rh factor IIa, produced in CHO cells

ZymoGenetics (Seattle)

Control of minor bleeding during surgery

2008 (US)

NovoSeven (eptacog alfa, activated), rh factor VIIa, produced in BHK cells

Novo Nordisk

Some forms of hemophilia

1996 (EU)

1999 (US)

Benefix (nonacog alfa), rh factor IX, produced in CHO cells

Pfizer/Wyeth

Hemophilia B

1997 (EU & US)

Metalyse (tenecteplase), modified rh tPA, produced in CHO cells

Boehringer Ingelheim (Ingelheim, Germany)

Myocardial infarction

2001 (EU)

Withdrawn 2005

TNKase (tenecteplase), modified rh tPA, produced in CHO cells

Roche/Genentech (South San Francisco, CA, USA)

Myocardial infarction

2000 (US)

Ecokinase (reteplase), r tPA, produced in Escherichia coli; differs from human tPA in that 3 of its 5 domains have been deleted

Roche (Welwyn Garden City, UK)

Acute myocardial infarction

1996 (EU)

Withdrawn 2000

Rapilysin (reteplase), r tPA (see Ecokinase above)

Actavis Group PTC (Hafnarfjordur, Iceland), Roche

Acute myocardial infarction

1996 (EU)

Retavase (reteplase), r tPA (see Ecokinase above)

Chiesi USA (Cary, NC, USA)

Acute myocardial infarction

1996 (US)

Activase (alteplase), rh tPA, produced in CHO cells

Roche/Genentech

Acute myocardial infarction

1987 (US)

Refludan (lepirudin), r hirudin, produced in S. cerevisiae

Celgene Europe (Windsor, UK) Bayer HealthCare

Anticoagulation therapy for heparin-associated thrombocytopenia

1997 (EU)

1998 (US)

Withdrawn 2012 (EU)

Revasc (desirudin), r hirudin, produced in S. cerevisiae

Canyon Pharmaceuticals (London)

Prevention of venous thrombosis

1997 (EU)

Withdrawn 2014

Ruconest (conestat alfa), rh C1 esterase inhibitor, produced in the milk of transgenic rabbits

Santarus (Raleigh, NC, USA) Pharming Group (Leiden, the Netherlands)

Acute angioedema

2014 (US) 2010 (EU)

Jetrea (ocriplasmin), r truncated form of human plasmin, produced in Pichia pastoris

ThromboGenics (Leuven, Belgium)

Symptomatic vitreomacular adhesion, vitreomacular traction

2013 (EU)

2012 (US)

Atryn (rh antithrombin), produced in milk of transgenic goats

Laboratoire français du fractionnement et des biotechnologies (Les Ulis, France), rEVO Biologics (Framingham, MA, USA)

Hereditary antithrombin deficiency

2009 (US)

2006 (EU)

Kalbitor (ecallantide), plasma kallikrein inhibitor, produced in P. pastoris

Dyax (Cambridge, MA, USA)

Hereditory angioedema

2009 (US)

Xigris (drotrecogin alfa), rh activated protein C, produced in a human cell line

Eli Lilly (Houten, the Netherlands)

Severe sepsis

2001 (US)

2002 (EU)

Withdrawn 2012 (EU)

Semglee (insulin glargine), r insulin glargine, produced in P. pastoris, biosimilar to Lantus

Mylan (Saint-Priest, France)

Diabetes mellitus

2018 (EU)

Admelog (insulin lispro injection), rapid-acting human insulin analog, produced in E. coli

Sanofi (Bridgewater, NJ, USA)

Diabetes mellitus

2017 (US)

Fiasp (insulin aspart injection), rapid-acting insulin analog, produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

2017 (US)

Insulin lispro Sanofi, produced in E. coli, biosimilar to Humalog

Sanofi-Aventis (Paris)

Diabetes mellitus

2017 (EU)

Lusduna (insulin glargine), engineered insulin, produced in E. coli, biosimilar to Lantus

Merck Sharp & Dohme (Hoddesdon, UK)

Diabetes mellitus

2017 (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 analog

Sanofi-Aventis (Paris) Sanofi (Bridgewater, NJ, USA)

Diabetes mellitus type 2

2017 (EU) 2016 (US)

Xultophy (insulin degludec/liraglutide), a combination of 2 previously approved products, Victoza and Tresiba

Novo Nordisk

Diabetes mellitus type 2

2016 (US) 2014 (EU)

Abasaglar (previously Abasria) in EU, Basaglar in US (insulin glargine), produced in E. coli, biosimilar (in EU) to Lantus

Eli Lilly (Indianapolis), Boehringer Ingelheim (Ridgefield, CT, USA) Eli Lilly (Vienna)

Diabetes mellitus

2015 (US) 2014 (EU)

Ryzodeg 70/30 in US, Ryzodeg in EU (insulin degludec/insulin aspart), combination of two engineered insulins, produced in S. cerevesiae

Novo Nordisk

Diabetes mellitus type 1 and 2

2015 (US) 2013 (EU)

Toujeo (insulin glargine), produced in E. coli

Sanofi (Bridgewater, NJ, USA)

Diabetes mellitus

2015 (US)

Tresiba (insulin degludec), engineered long-acting human insulin analog, produced in S. cerevisiae (see also Ryzodeg above)

Novo Nordisk

Diabetes mellitus type 1 and 2

2015 (US) 2013 (EU)

Afrezza (rh insulin), produced in E. coli

MannKind (Danbury, CT, USA)

Diabetes mellitus

2014 (US)

Novolog mix (insulin aspart mix), a 50:50 mixture of engineered rh insulin, produced in S. cerevisiae in soluble and protamine suspension forms

Novo Nordisk

Diabetes mellitus

2008 (US)

Insulin Human Winthrop (rh insulin), produced in E. coli

Sanofi (Frankfurt)

Diabetes mellitus

2007 (EU)

Withdrawn 2018

Exubera (inhalable rh insulin), produced in E. coli

Pfizer (Sandwich, UK)

Diabetes mellitus

2006 (EU & US)

Withdrawn 2008 (EU)

Levemir (insulin detemir), long-acting rh insulin, produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

2005 (US)

2004 (EU)

Apidra (insulin glulisine), rapid-acting insulin analog, produced in E. coli

Sanofi (Frankfurt)

Diabetes mellitus

2004 (EU & US)

Actrapid, Velosulin, Monotard, Insulatard, Protaphane, Mixtard, Actraphane, Ultratard: rh insulin formulated as short-, intermediate- or long-acting product, produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

2002 (EU)

Monotard and Ultratard withdrawn 2006

Velosulin withdrawn 2009

Novolog (insulin aspart), short-acting rh insulin analog, produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

2001 (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 Nordisk

Diabetes mellitus

2001 (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 Nordisk

Diabetes mellitus

2000 (EU)

Lantus (insulin glargine), long-acting rh insulin analog, produced in E. coli

Sanofi (Frankfurt)

Diabetes mellitus

2000 (EU & US)

Optisulin (insulin glargine), long-acting rh insulin analog, produced in E. coli (see also Lantus above)

Sanofi (Frankfurt)

Diabetes mellitus

2000 (EU)

NovoRapid (insulin aspart), rh insulin analog), produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

1999 (EU)

Liprolog (insulin lispro), insulin analog, produced in E. coli

Eli Lilly (Houten, the Netherlands)

Diabetes mellitus

1997 (EU)

Withdrawn 2001

Insuman (rh insulin), produced in E. coli

Sanofi (Frankfurt)

Diabetes mellitus

1997 (EU)

Humalog (insulin lispro), insulin analog, produced in E. coli

Eli Lilly (Houten, the Netherlands)

Diabetes mellitus

1996 (EU & US)

Novolin (rh insulin), produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus

1991 (US)

Withdrawn 2010

Humulin (rh insulin), produced in E. coli

Eli Lilly (Indianapolis)

Diabetes mellitus

1982 (US)

Somatropin Biopartners (somatropin), r hGH, produced in S. cerevisiae

Biopartners (Reutlingen, Germany)

Growth failure, growth hormone deficiency

2013 (EU)

Withdrawn 2017

Accretropin (somatropin), r hGH, produced in E. coli

Emergent Biosolutions (Rockville, MD, USA) Cangene (Winnipeg, MB, Canada)

Growth failure or short stature associated with Turner syndrome in children

2008 (US)

Valtropin (somatropin), r hGH, produced in S. cerevisiae, biosimilar to Humatrope

Biopartners

LG Life Sciences (Reutlingen, Germany)

Certain forms of growth disturbance in children and adults

2007 (US)

2006 (EU)

Withdrawn 2012 (EU)

Omnitrope (somatropin), r hGH, produced in E. coli, biosimilar (in EU) to Genotropin

Sandoz (Kundl, Austria) Novartis (Princeton, NJ, USA)

Certain forms of growth disturbance in children and adults

2006 (EU & US)

Somavert (pegvisomant), PEGylated r hGH analog (antagonist), produced in E. coli

Pfizer (Brussels & New York) Nektar Therapeutics (San Francisco)

Acromegaly

2003 (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 syndrome

2001 (EU)

1994 (US)

Withdrawn 2008 (EU)

Serostim (somatropin), r hGH, produced in mouse C127 cells

EMD Serono (Geneva)

AIDS-associated catabolism and wasting

1996 (US)

Saizen (somatropin), r hGH, produced in mouse C127 cells

EMD Serono (Rockland, MA, USA)

hGH deficiency in children

1996 (US)

Genotropin (somatropin), r hGH, produced in E. coli

Pfizer (New York)

hGH deficiency in children

1995 (US)

Norditropin (somatropin), r hGH, produced in E. coli

Novo Nordisk

Growth failure in children due to inadequate growth hormone secretion

1995 (US)

Tev-Tropin, Bio-tropin (somatropin), r hGH, produced in E. coli

Teva Pharmaceuticals (North Wales, PA, USA)

hGH deficiency in children

1995 (US)

Nutropin (somatropin), r hGH, produced in E. coli

Roche/Genentech

hGH deficiency in children

1994 (US)

Humatrope (somatropin), r hGH, produced in E. coli

Eli Lilly (Indianapolis)

hGH deficiency in children

1987 (US)

Protropin (somatrem), r hGH differing from hGH by an extra N-terminal methionine, produced in E. coli

Genentech

hGH deficiency in children

1985 (US)

Withdrawn 2004

Rekovelle (follitropin delta), rh FSH, produced in PER.C6 cells

Ferring Pharmaceuticals (Copenhagen)

Anovulation

2016 (EU)

Bemfola (follitropin alfa), rh FSH, produced in CHO cells, biosimilar to Gonal F

Finox Biotech (Burgdorf, Switzerland)

Anovulation (women), failure of spermatogenesis (men)

2014 (EU)

Ovaleap (follitropin alfa), rh FSH, produced in CHO cells, biosimilar to Gonal F

Teva Pharma (Utrect, the Netherlands)

Infertility, subfertility

2013 (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 cells

Merck Sharp & Dohme

Controlled ovarian stimulation

2010 (EU)

Fertavid (follitropin beta), rh FSH, produced in CHO cells. Active substance same as that in Puregon (see below)

Merck Sharp & Dohme

Infertility

2009 (EU)

Pergoveris (follitropin alfa/lutropin alfa) combination product containing rh FSH and rh luteinizing hormone, both produced in CHO cells

Merck Serono (London)

Stimulation of follicular development in women with severe luteinizing hormone and FSH deficiency

2007 (EU)

Follistim (follitropin beta), rh FSH, produced in CHO cells

Merck (Whitehouse Station, NJ, USA)

Infertility

1997 (US)

Puregon (follitropin beta), rh FSH, produced in CHO cells

Merck Sharp & Dohme (Haarlem, the Netherlands)

Anovulation and superovulation

1996 (EU)

Gonal F (follitropin alfa), rh FSH, produced in CHO cells

Merck Serono EMD Serono (Rockland, MD, USA)

Anovulation and superovulation

1997 (US)

1995 (EU)

Myalepta in EU, Myalept in US (metreleptin), rh leptin analog, produced in E. coli

Aegerion Pharmaceuticals (Amsterdam & Cambridge, MA, USA)

Some forms of lipodystrophy

2018 (EU) 2014 (US)

Ozempic (semaglutide), human GLP-1 receptor agonist, produced in yeast and covalently modified by attachment of a C18 fatty acid

Novo Nordisk

Diabetes mellitus type 2

2018 (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)

Osteoporosis

2017 (EU)

Natpar (parathyroid hormone), rh parathyroid hormone, full length, produced in E. coli. Same product as Preotact (see below).

Shire Pharmaceuticals Ireland (Dublin)

Hypoparathyroidism

2017 (EU)

Terrosa (teriparatide), rh parathyroid hormone fragment, produced in E. coli, biosimilar to Fortseo. Same product as Movymia (see above)

Gedeon Richter (Budapest)

Osteoporosis

2017 (EU)

Natpara (parathyroid hormone), rh parathyroid hormone, produced in E. coli

Shire-NPS Pharmaceuticals (Lexington, MA, USA)

Hypocalcemia

2015 (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 Nordisk

Obesity

2015 (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. cerevisiae

GSK (Carrigaline, Ireland, & Research Triangle Park, NC, USA)

Diabetes mellitus type 2

2014 (EU & US)

Trulicity (dulaglutide), fusion protein consisting of a GLP-1 analog linked to a human IgG Fc domain, produced in a mammalian cell line

Eli Lilly (Utrecht, the Netherlands, & Indianapolis)

Diabetes mellitus type 2

2014 (EU & US)

Gattex in US, Revestive in EU (teduglutide), rh GLP-2 analog, produced in E. coli

NPS Pharma (Dublin)

Short bowel syndrome

2012 (EU & US)

Victoza (liraglutide), GLP-1 analog with attached fatty acid, produced in S. cerevisiae

Novo Nordisk

Diabetes mellitus type 2

2010 (US)

2009 (EU)

Preotact, rh parathyroid hormone, produced in E. coli

NPS Pharma

Osteoporosis

2006 (EU)

Withdrawn 2014

Fortical, r salmon calcitonin, produced in E. coli

Upsher-Smith Laboratories (Minneapolis) Unigene Laboratories (Fairfield, NJ, USA)

Postmenopausal osteoporosis

2005 (US)

Luveris (lutropin alfa), rh luteinizing hormone, produced in CHO cells

EMD Serono (Rockland, MA, USA) Merck Europe (Amsterdam)

Some forms of infertility

2004 (US)

2000 (EU)

Forsteo in EU, Forteo in US (teriparatide), r shortened human parathyroid hormone, produced in E. coli

Eli Lilly (Houten, the Netherlands)

Established osteoporosis in some postmenopausal women

2003 (EU)

2002 (US)

Natrecor (nesiritide), rh natriuretic peptide, produced in E. coli

Johnson & Johnson/Scios (Titusville, NJ, USA)

Acutely decompensated congestive heart failure

2001 (US)

Ovitrelle in EU, Ovidrel in US (choriogonadotropin alfa) rh chorionic gonadotropin, produced in CHO cells

Merck Serono

Selected assisted reproductive techniques

2001 (EU)

2000 (US)

Thyrogen (thyrotropin alfa), rh thyroid-stimulating hormone, produced in CHO cells

Sanofi Genzyme (Cambridge, MA, USA)

Thyroid cancer (detection and treatment)

1998 (US)

2000 (EU)

Forcaltonin, r salmon calcitonin, produced in E. coli

Unigene UK (Bushey Heath, UK)

Paget disease

1999 (EU)

Withdrawn 2008

Glucagen, rh glucagon, produced in S. cerevisiae

Novo Nordisk

Hypoglycemia

1998 (US)

Glucagon (glucagon, recombinant), rh glucagon, produced in E. coli

Eli Lilly (Indianapolis)

Hypoglycemia

1998 (US)

Retacrit (epoetin zeta in EU, epoetin alfa-epbx in US), rh EPO, produced in CHO cells, biosimilar to Eprex and Erypo

Hospira (Royal Leamington Spa, UK) Pfizer (Lake Forest, IL, USA)

Anemia

2018 (US) 2007 (EU)

Biopoin (epoetin theta), rh EPO, produced in CHO cells

Teva (Ulm, Germany)

Anemia

2009 (EU)

Eporatio (epoetin theta), rh EPO, produced in CHO cells

Teva (Ulm, Germany)

Anemia

2009 (EU)

Abseamed (epoietin alfa), produced in CHO cells, biosimilar to Eprex/Erypo

Medice Arzneimittel Pütter (Iserlon, Germany)

Anemia associated with chronic renal failure

2007 (EU)

Binocrit (epoetin alfa), produced in CHO cells, biosimilar to Eprex/Erypo

Sandoz

Anemia associated with chronic renal failure

2007 (EU)

Epoetin alfa Hexal (epoietin alfa), produced in CHO cells, biosimilar to Eprex/Erypo

Hexal (Holzkirchen, Germany)

Anemia associated with chronic renal failure

2007 (EU)

Mircera (methoxy polyethylene glycol-epoetin beta) PEGylated rh EPO, produced in CHO cells

Roche (Welwyn Garden City, UK)

Anemia associated with chronic kidney disease

2007 (EU & US)

Silapo (epoetin zeta), produced in CHO cells, biosimilar to Eprex/Erypo

STADA (Bad Vilbel, Germany) yes

Anemia associated with chronic renal failure

2007 (EU)

Dynepo (epoetin delta), rh EPO, produced in a human cell line

Shire Pharmaceuticals (Basingstoke, UK)

Anemia

2002 (EU)

Withdrawn 2009

Aranesp (darbepoetin alfa), long-acting r EPO analog, produced in CHO cells (see Nespo below)

Amgen (Breda, the Netherlands)

Anemia

2001 (EU & US)

Nespo (darbepoetin alfa), long-acting r EPO analog, produced in CHO cells (see Aranesp above)

Dompé Biotec (Milan)

Anemia

2001 (EU)

Withdrawn 2008

Neorecormon (epoietin beta), rh EPO, produced in CHO cells

Roche

Anemia

1997 (EU)

Procrit (epoietin alfa), rh EPO, produced in a mammalian cell line

Janssen Biotech (Horsham, PA, USA)

Anemia

1990 (US)

Epogen (epoietin alfa), rh EPO, produced in CHO cells

Amgen

Anemia

1989 (US)

Fulphila (pegfilgrastim-jmdb), PEGylated rh G-CSF, produced in E. coli, biosimilar to Neulasta

Mylan (Rockford, IL USA)

Neutropenia

2018 (US)

Nivestym (filgrastim-aafi) in US, Nivestim (filgrastim) in EU: rh G-CSF, produced in E. coli, biosimilar to Neupogen

Pfizer (Lake Forest, IL, USA) Hospira (Royal Leamington Spa, UK)

Neutropenia

2018 (US) 2010 (EU)

Ristempa (pegfilgrastim), covalent conjugate of rh G-CSF, produced in E. coli and conjugated to 20-kDa polyethylene glycol

Amgen (Breda, the Netherlands)

Neutropenia

2015 (EU) Withdrawn 2017

Zarxio in US, Zarzio in EU (filgrastim-sndz), rh G-CSF, produced in E. coli

Sandoz (Princeton, NJ, USA, & Kundl, Austria)

Neutropenia

2015 (US) 2009 (EU)

Accofil (filgrastim), G-CSF, produced in E. coli, biosimilar to Neupogen. Same product as Grastofil (see below)

Accord Healthcare (Ahmedabad, India)

Neutropenia

2014 (EU)

Grastofil (filgrastim), rh G-CSF, produced in E. coli, biosimilar to Neupogen. Same product as Accofil (see above)

Apotex (Leiden, the Netherlands)

Neutropenia

2013 (EU)

Lonquex (lipegfilgrastim), PEGylated rh G-CSF, produced in E. coli

Teva Pharma (Utrect, the Netherlands)

Neutropenia

2013 (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)

Neutropenia

2012 (US)

Filgrastim Hexal (filgrastim), produced in E. coli, biosimilar to Neupogen

Hexal

Neutropenia

2009 (EU)

Biograstim (filgrastim), produced in E. coli, biosimilar to Neupogen

ABZ-Pharma (Ulm, Germany)

Neutropenia

2008 (EU)

Withdrawn 2015

Ratiograstim (filgrastim), produced in E. coli, biosimilar to Neupogen

Ratiopharm (Ulm, Germany)

Neutropenia

2008 (EU)

Tevagrastim (filgrastim), produced in E. coli, biosimilar to Neupogen. Same product as Granix (see above)

Teva (Radebeul, Germany)

Neutropenia

2008 (EU)

Filgrastim Ratiopharm (filgrastim), produced in E. coli, biosimilar to Filgrastim

Ratiopharm

Neutropenia

2008 (EU)

Withdrawn 2011

Neulasta in EU and US, Neupopeg in EU (pegfilgrastim), PEGylated rh G-CSF

Amgen (Breda, the Netherlands)

Chemotherapy-induced neutropenia

2002 (EU & US)

Neupopeg withdrawn 2008 (EU)

Leukine (sargramostim), rh GM-CSF differing from the native protein by an R23L substitution, produced in E. coli

Sanofi-aventis U.S. (Bridgewater, NJ, USA)

Autologous bone marrow transplantation

1991 (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. coli

Amgen (Thousand Oaks, CA, USA)

Chemotherapy-induced neutropenia

1991 (US)

Oxervate (cenegermin), rh nerve growth factor, produced in E. coli

Dompé Farmaceutici (Milan)

Neurotophic keratitis

2017 (EU)

Increlex (mecaserim), rh IGF-1, produced in E. coli

Ipsen Pharma

Growth 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. coli

Insmed (Glen Allen, VA, USA)

Growth failure in children with severe primary IGF-1 deficiency or hGH gene deletion (long-term treatment

2005 (US)

Withdrawn 2007 for IGF-1 deficiency

Kepivance (palifermin), rh keratinocyte growth factor, produced in E. coli

Swedish Orphan Biovitrum

Severe oral mucositis in selected patients with hematologic cancers

2005 (EU)

2004 (US)

Withdrawn 2016 (EU)

GEM 21S: Regranex (see below) and tricalcium phosphate; growth-factor-enhanced matrix

BioMimetic Pharmaceuticals (Franklin, TN, USA)

Periodonatally related defects

2005 (US)

Regranex (becaplermin), rh platelet-derived growth factor receptor-BB, produced in S. cerevisiae

Johnson & Johnson (Raritan, NJ, USA) Janssen-Cilag International (Beerse, Belgium)

Lower extremity diabetic neuropathic ulcers

1997 (US)

1999 (EU)

Withdrawn 2012 (EU)

PEG-Intron/Rebetol combo pack (peginterferon alfa-2b/ribavirin) PEGylated rh IFN-α-2b, produced in E. coli, and ribavirin

Schering Plough (Kenilworth, NJ, USA)

Chronic hepatitis C

2008 (US)

Pegasys (peginterferon alfa-2a), PEGylated IFN-α-2b, produced in E. coli

Roche/Genentech (Welwyn Garden City, UK)

Hepatitis C

2002 (EU & US)

PEG-Intron (peginterferon alfa-2b), PEGylated IFN-α-2b, produced in E. coli.

Merck Sharp & Dohme

Chronic hepatitis C

2001 (US)

2000 (EU)

Viraferon (interferon alfa-2b), produced in E. coli

Schering Plough (Brussels, Belgium)

Chronic hepatitis B, C

2000 (EU)

Withdrawn 2008

ViraferonPeg (peginterferon alfa-2b), PEGylated IFN-α-2b, produced in E. coli

Merck Sharp & Dohme

Chronic hepatitis C

2000 (EU)

Intron A, Alfatronol (interferon alfa-2b), produced in E. coli

Merck Sharp & Dohme

Cancer, genital warts, hepatitis B and C, HPV

2000 (EU)

1986 (US)

Rebetron (ribavirin/interferon alfa-2b), produced in E. coli

Schering Plough

Chronic hepatitis C

1999 (US)

Infergen (interferon alficon-1), r IFN-α, synthetic type I, produced in E. coli

Astellas Pharma Europe (Leiderdorp, the Netherlands) Kadmon Pharmaceuticals (Warrendale, PA, USA)

Chronic hepatitis C

1999 (EU)

1997 (US)

Withdrawn 2006 (EU)

Roferon A (interferon alfa-2a), produced in E. coli

Roche

Hairy cell leukemia

1986 (US)

Withdrawn 2007

Plegridy (peginterferon beta-1a), rh PEGylated IFN- β-1a, produced in CHO cells

Biogen Idec (Maidenhead, UK)

Multiple sclerosis

2014 (EU & US)

Extavia (interferon beta-1b), rh IFN β-1b, produced in E. coli

Novartis Europharm (Camberley, UK) Novartis Pharmaceuticals (East Hanover, NJ, USA)

Multiple sclerosis

2009 (US)

2008 (EU)

Rebif (interferon beta-1a), rh IFN-β-1a, produced in CHO cells

EMD Serono (London)

Relapsing/remitting multiple sclerosis

2002 (US)

1998 (EU)

Avonex (interferon beta-1a), rh IFN-β-1a, produced in CHO cells

Biogen Idec (Maidenhead, UK)

Relapsing multiple sclerosis

1997 (EU)

1996 (US)

Betaferon (interferon beta-1b), r IFN-β-1b differing from native protein by C17S, produced in E. coli

Bayer Pharma

Multiple sclerosis

1995 (EU)

Betaseron (interferon beta-β-1b), differing from human protein by C17S, produced in E. coli

Berlex Laboratories (Richmond, CA, USA) Chiron (Emeryville, CA, USA)

Relapsing/remitting multiple sclerosis

1993 (US)

Actimmune (interferon gamma-1b), produced in E. coli

Vidara Therapeutics (Dublin)

Chronic granulomatous disease

1990 (US)

Kineret (anakinra), rh IL-1 receptor antagonist, produced in E. coli

Swedish Orphan Biovitrum

Rheumatoid arthritis

2001 (US)

Beromun (tasonermin), rh TNF-α, produced in E. coli

Boehringer Ingelheim (Ingelheim, Germany)

Adjunct to surgery for subsequent tumor removal to prevent or delay amputation

1999 (EU)

Neumega (oprelvekin), r IL-11 lacking N-terminal proline of native molecule, produced in E. coli

Pfizer (Philadelphia), Genetics Institute

Prevention of chemotherapy-induced thrombocytopenia

1997 (US)

Proleukin (aldesleukin) r IL-2, differs from native molecule in absence of N-terminal alanine and presence of C125S substitution, produced in E. coli

Prometheus Laboratories (San Diego)

Renal cell carcinoma

1992 (US)

HEPLISAV-B (hepatitis B vaccine (recombinant) adjuvanted), HBsAg, produced in Hansenula polymorpha yeast

Dynavax Technologies (Berkeley, CA, USA)

Prevention of infection caused by all known subtypes of hepatitis B virus

2017 (US)

Hexacima, also sold as Hexyon, multi-component vaccine containing r HBsAg, produced in H. polymorpha as one component

Sanofi Pasteur (Lyon, France)

Immunization against several pathogens and toxins

2013 (EU)

Ambirix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK (Rixensart, Germany)

Immunization against hepatitis A and B

2002 (EU)

Pediarix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization of children against various conditions inducing hepatitis B

2002 (US)

HBVAXPRO (r HBsAg), produced in S. cerevisiae

Sanofi Pasteur

Immunization of children and adolescents against hepatitis B

2001 (EU)

Twinrix, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization against hepatitis A and B

2001 (US)

1997 (EU pediatric form)

1996 (EU adult form)

Infanrix-hexa, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae b, hepatitis B and polio

2000 (EU)

Infanrix-penta, combination vaccine, containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization against diphtheria, tetanus, pertussis, polio, and hepatitis B

2000 (EU)

Withdrawn 2013

Hepacare (r S, pre-S & pre-S2 HBsAg), produced in a murine cell line

Evans Vaccines (Liverpool, UK)

Immunization against hepatitis B

2000 (EU)

Withdrawn 2002

Hexavac, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

Sanofi Pasteur

Immunization against diphtheria, tetanus, pertussis, hepatitis B, polio and H. influenzae b

2000 (EU)

Withdrawn 2012

Procomvax, combination vaccine containing r HBsAg as one component

Sanofi Pasteur

Immunization against H. influenzae b and hepatitis B

1999 (EU)

Withdrawn 2009

Primavax, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

Sanofi Pasteur

Immunization against diphtheria, tetanus and hepatitis B

1998 (EU)

Withdrawn 2000

Engerix B, r HBsAg, produced in S. cerevisiae

GSK

Immunization against hepatitis B

1998 (US)

Infanrix Hep B, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization against diphtheria, tetanus, pertussis and hepatitis B

1997 (EU)

Withdrawn 2005

Comvax, combination vaccine containing HBsAg, produced in S. cerevisiae as one component

Merck (Whitehouse Station, NJ, USA)

Immunization of infants against H. influenzae b and hepatitis B

1996 (US)

Tritanrix-Hep B, combination vaccine containing r HBsAg, produced in S. cerevisiae as one component

GSK

Immunization against hepatitis B, diphtheria, tetanus and pertussis

1996 (EU)

Withdrawn 2014

Recombivax, r HBsAg, produced in S. cerevisiae

Merck (WhitehouseStation, NJ, USA)

Immunization against hepatitis B

1986 (US)

Shingrix (zoster vaccine recombinant, adjuvanted), recombinant varicella zoster virus surface glycoprotein E antigen component, produced in CHO cells

GlaxoSmithKline 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. coli

Pfizer (Philadelphia)

Vaccine against N. meningitides serogroup B

2017 (EU) 2014 (US)

Pandemic influenza vaccine H5N1, vaccine derived from engineered viral strain containing gene segments from appropriate viral influenza strains, produced in embryonated eggs

MedImmune (Nijmegen, the Netherlands

Influenza vaccine

2016 (EU)

Bexsero (meningococcal group B vaccine), mixture of 3 N. meningitidis serogroup B proteins, produced in E. coli

Novartis (Cambridge, MA, USA, & Siena, Italy)

Active immunization against N. meningitidis serogroup B

2015 (US) 2013 (EU)

Gardasil 9, mixture of the major capsid protein (L1) of 9 strains of HPV, each produced in S. cerevisiae

MSD (Lyon, France) Merck (Whitehouse Station, NJ, USA)

Active immunization for those above 9 years of age against HPV-caused cancers and genital warts

2015 (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. cerevisiae

GlaxoSmithKline Biologicals (Rixensart, Belgium)

Vaccination against malaria caused by the parasite Plasmodium falciparum

2015 (EU); approved for use outside the EU

Flublok, r hemagglutinin proteins from 3 influenza viruses, produced in an insect cell line

Protein Sciences (Meriden, CT, USA)

Immunization against influenza

2013 (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 line

Dendreon (London)

Prostate cancer

2013 (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 system

GSK

Prevention of cervical cancer

2009 (US)

2007 (EU)

Gardasil in EU & US, Silgard in EU, r vaccine containing major capsid proteins from four HPV types, produced in S. cerevisiae

Sanofi Pasteur Merck (Whitehouse Station, NJ, USA)

Vaccination against diseases caused by HPX

2006 (EU & US)

Dukoral (Vibrio cholerae and r cholera toxin B subunit)

Valneva Sweden (Stockholm)

Immunization against disease caused by V. cholerae subunit O1

2004 (EU)

Lymerix (r OspA), a lipoprotein found on the surface of B. burgdorferi, produced in E. coli

GSK

Immunization against Lyme disease

1998 (US)

Withdrawn 2002

Triacelluvax, combination vaccine containing r modified pertussis toxin as one component

Chiron (Siena, Italy)

Immunization against diphtheria, tetanus and pertussis

1999 (EU)

Withdrawn 2002

Aimovig (erenumab-aooe in USA, erenumab in EU), human IgG2 targeting the calcitonin gene-related peptide receptor, produced in CHO cells

Amgen (Thousand Oaks, CA, USA) Novartis (East Hanover, NJ, USA) Novartis Europharm (Dublin)

Migraine

2018 (EU & US)

Crysvita (burosumab in EU, burosumab-twza in USA), human IgG1 antibody to soluble fibroblast growth factor-23, produced in CHO cells

Kyowa Kirin (Galashiels, UK) Ultragenyx Pharmaceutical (Novato, CA, USA)

X-linked hypophosphatemia

2018 (EU & US)

Fasenra (benralizumab), humanized, afucosylated IgG1 targeting the α subunit of the human IL-5 receptor, produced in CHO cells

AstraZeneca (Södartälje, Sweden, & Wilmington, DE, USA)

Asthma

2018 (EU) 2017 (US)

Halimatoz (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Hefiya and Hyrimoz (see below)

Sandoz

Various inflammatory conditions mediated by TNF, including rheumatoid arthritis and plaque psoriasis

2018 (EU)

Hefiya (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Halimatoz and Hyrimoz (see above and below)

Sandoz

Various inflammatory conditions mediated by TNF, including polyarticular juvenile idiopathic arthritis and plaque psoriasis

2018 (EU)

Hemlibra (emicizumab in EU, emicizumab-kxwh in US), humanized, bispecific IgG4 capable of binding factor IXa and factor X, produced in CHO cells

Roche Registration (Welwyn Garden City, UK) Roche/Genentech (South San Francisco, CA, USA)

Hemophilia A

2018 (EU) 2017 (US)

Herzuma (trastuzumab), r humanized IgG1 against HER2, produced in CHO cells, biosimilar to Herceptin

Celltrion Healthcare (Budapest)

Breast and gastric cancers

2018 (EU)

Hyrimoz (adalimumab), anti-TNF IgG, produced in CHO cells, biosimilar to Humira. Same product as Halimatoz and Hefiya (see above)

Sandoz

Various inflammatory conditions mediated by TNF, including rheumatoid arthritis and plaque psoriasis

2018 (EU)

Ilumya (tildrakizumab-asmn), humanized IgG1 that binds the p19 subunit of IL-23, produced in CHO cells

Merck (Whitehouse Station, NJ, USA)

Plaque psoriasis

2018 (US)

Kanjinti (trastuzumab), r humanized IgG1 against HER2, produced in CHO cells, biosimilar to Herceptin

Amgen Europe (Breda, the Netherlands)

Breast and gastric cancers

2018 (EU)

Mvasi (bevacizumab in EU, bevacizumab-awwb in US), humanized IgG antibody to human VEGF-A1, produced in CHO cells, biosimilar to Avastin

Amgen EuropeAmgen (Thousand Oaks, CA, USA)

Various cancers

2018 (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 cells

Pfizer Europe (Brussels) Pfizer/Wyeth (Philadelphia)

Acute myeloid leukemia

2018 (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 cells

Roche Registration Genentech (South San Francisco, CA, USA)

Multiple sclerosis

2018 (EU) 2017 (US)

Trazimera (trastuzumab), humanized IgG, produced in a CHO cells, biosimilar to Herceptin

Pfizer (Brussels)

Breast cancer, gastric or gastro-esophageal junction adenocarcinoma

2018 (EU)

TROGARZO (ibalizumab-uiyk), humanized IgG4 targeting the CD4 domain, produced in NS0 cells

TaiMed Biologics (Irvine, CA, USA) Theratechnologies (Montreal)

Human immunodeficiency virus type 1 infection

2018 (US)

Zessly (infliximab), chimeric anti-TNF IgG1 produced in CHO cells, biosimilar to Remicade (infliximab)

Sandoz

Rheumatoid arthritis and selected additional inflammatory diseases

2018 (EU)

Amgevita (adalimumab), anti-TNF human IgG1, produced in CHO cells, biosimilar to Humira. Same product as Solymbic and Amjevita (see below)

Amgen Europe

Rheumatoid arthritis and selected additional inflammatory diseases

2017 (EU)

Bavencio (avelumab), human IgG1 specific for programmed death ligand-1 (PD-L1), produced in CHO cells

Merck Europe (Amsterdam) Pfizer (New York)

Metastatic Merkel cell carcinoma, urothelial carcinoma

2017 (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 dimethylhydrazide

Pfizer (Sandwich, UK) Pfizer/Wyeth (Philadelphia)

Acute lymphoblastic leukemia

2017 (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, granulomatosis

2017 (EU)

Cyltezo (adalimumab in EU, adalimumab-adbm in USA), rh IgG1 against human TNF, produced in CHO cells, biosimilar to Humira

Boehringer Ingelheim (Rhein, Germany) Boehringer Ingelheim (Ridgefield, CT, USA)

Range of inflammatory conditions, including psoriasis, rheumatoid arthritis and Crohn's disease

2017 (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)

Neuroblastoma

2017 (EU)

Dupixent (dupilumab), human IgG4 that binds the IL-4α receptor subunit, produced in CHO cells

Sanofi-Aventis (Paris & Bridgewater, NJ, USA), Regeneron Pharmaceuticals (Tarrytown, NY, USA)

Atopic dermatitis

2017 (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 cells

AstraZeneca (Wilmington, DE, USA)

Urothelial carcinoma

2017 (US)

Imraldi (adalimumab), produced in CHO cells, biosimilar to Humira

Samsung Bioepis UK (Chertsey, UK)

Rheumatoid arthritis, selected additional inflammatory diseases

2017 (EU)

Ixifi (infliximab-qbtx), produced in a mammalian cell line, biosimilar to Remicade

Pfizer (New York)

Various inflammatory conditions, including rheumatoid arthritis, Crohn's disease and psoriasis

2017 (US)

Kevzara (sarilumab), human IgG1 that binds IL-6 receptors, produced in CHO cells

Sanofi-Aventis (Paris & Bridgewater, NJ, USA), Regeneron Pharmaceuticals (Tarrytown, NY, USA)

Rheumatoid arthritis

2017 (EU) 2017 (US)

Kyntheum in EU, Siliq in US (brodalumab), human IgG2 against human IL-17 receptor A, produced in CHO cells

LEO Pharma (Ballerup, Denmark) Valeant Pharmaceuticals (Bridgewater, NJ, USA)

Psoriasis

2017 (EU) 2017 (US)

Ogivri (trastuzumab-dkst), produced in CHO cells, biosimilar to Herceptin

Mylan (Morgantown, WV, USA, & Zurich)

Breast and gastric cancers

2017 (US)

Ontruzant, produced in CHO cells, biosimilar to Herceptin

Samsung Bioepis UK (Brentford, UK)

Breast and gastric cancers

2017 (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 cells

EUSA Pharma (Hemel Hempstead, UK)

Neuroblastoma

2017 (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 conditions

2017 (US)

Ritemvia (rituximab), produced in CHO cells, biosimilar to MabThera. Same product as Blitzima, Rituzena and Truxima (see above and below)

Celltrion Healthcare Hungary

Non-Hodgkin lymphoma, granulomatosis with polyangiitis, microscopic polyangiitis

2017 (EU)

Rituxan Hycela (rituximab and hyaluronidase human), both produced in CHO cells

Biogen (Cambridge, MA, USA), Genentech

Follicular lymphoma, diffuse large B-cell lymphoma, CLL

2017 (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 Hungary

Non-Hodgkin lymphoma, CLL, granulomatosis with polyangiitis

2017 (EU)

Rixathon (rituximab), chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabThera. Same product as Riximyo (see below)

Sandoz

Various conditions including non-Hodgkin lymphoma, CLL, rheumatoid arthritis

2017 (EU)

Riximyo (rituximab), chimeric IgG1 against cell surface antigen CD20, produced in CHO cells, biosimilar to MabThera. Same product as Rixathon (see above)

Sandoz

Various conditions including non-Hodgkin lymphoma and rheumatoid arthritis, but excluding CLL

2017 (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 Europe

Rheumatoid arthritis and selected additional inflammatory diseases

2017 (EU)

Tecentriq (atezolizumab), humanized IgG1 specific for programmed death ligand 1 (PD-L1), engineered to lack Fc glycosylation, produced in CHO cells

Roche Registration (Grenzach-Wyhlen, Germany) Genentech (South San Francisco, CA, USA)

Urothelial carcinoma, non-small-cell lung cancer

2017 (EU) 2016 (US)

Tremfya (guselkumab), human IgG1 that selectively binds the p19 subunit of IL-23, produced in CHO cells

Janssen-Cilag (Beerse, Belgium) Janssen Biotech (Horsham, PA, USA)

Psoriasis

2017 (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)

Celltrion

Selected cancers and autoimmune disorders

2017 (EU)

Zinplava (bezlotoxumab), human IgG directed against Clostridium difficile toxin B, produced in CHO cells

Merck Sharp & DohmeMerck (Whitehouse Station, NJ, USA)

C. difficile infection

2017 (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 diseases

2016 (US)

Anthim (obiltoxaximab), chimeric IgG1 against Bacillus anthracis toxin, produced in NS0 cells

Elusys Therapeutics (Pine Brook, NJ, USA)

Inhalational anthrax

2016 (US)

Cinqair in US, Cinqaero in EU (reslizumab), humanized IgG4 against IL-5, produced in NS0 cells

Teva Respiratory (Frazer, PA USA) Teva (Haarlem, the Netherlands)

Asthma

2016 (US) 2016 (EU)

Darzalex (daratumumab), human IgG1 against CD-38, produced in CHO cells

Janssen-Cilag Janssen Biotech

Multiple myeloma

2016 (EU) 2015 (US)

Empliciti (elotuzumab) humanized IgG1 against the cell surface receptor SLAMF7, produced in NS0 cells

Bristol-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 spondylitis

2016 (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 Remicade

Inflectra: 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 spondylitis

2016 (US) 2013 (EU)

Lartruvo (olaratumab), rh IgG1 specific for human platelet-derived growth factor receptor-α, produced in NS0 cells

Eli Lilly (Utrecht, the Netherlands, & Indianapolis)

Sarcoma

2016 (EU & US)

Portrazza (necitumumab), human IgG1 against the ligand binding site of human EGF receptor, produced in NS0 cells

Eli 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 cells

Eli Lilly (Utrecht, the Netherlands, & Indianapolis)

Psoriasis

2016 (EU & US)

Zinbryta (daclizumab), humanized IgG1 against IL-2Rα, produced in NS0 cells

Biogen (Cambridge, MA US) Biogen Idec (Maidenhead, UK)

Multiple sclerosis

2016 (EU & US) Withdrawn 2018 (EU & US)

Blincyto (blinatumomab), bispecific T-cell engager antibody construct (BiTE), produced in CHO cells

Amgen Europe Amgen (Thousand Oaks, CA, USA)

Acute lymphoblastic leukemia

2015 (EU) 2014 (US)

Cosentyx (secukinumab), human IgG1 selectively binding human IL-17a, produced in CHO cells

Novartis Europharm (Camberley, UK) Novartis (East Hanover, NJ, USA)

Moderate to severe plaque psoriasis in adults

2015 (EU & US)

Keytruda (pembrolizumab), humanized IgG4 capable of binding to the receptor PD-1, produced in CHO cells

Merck Sharp & Dohme Merck (Whitehouse Station, NJ, USA)

Advanced (unresectable or metastatic) melanoma in adults

2015 (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 adults

July 2015 (EU) Withdrawn November 2015

Nucala (mepolizumab), humanized IgG1 capable of binding human IL-5, produced in CHO cells

GlaxoSmithKline (Cork, Ireland) GSK (Research Triangle Park, NC, USA)

Add-on treatment for severe refractory eosinophilic asthma in adult patients

2015 (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 carcinoma

2015 (EU) 2014 (US)

Praluent (alirocumab), human IgG1 targeting PCSK9, produced in CHO cells

Sanofi-Aventis (Paris & Bridgewater, NJ, USA) Regeneron Pharmaceuticals (Tarrytown, NY, USA)

Primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet

2015 (EU & US)

Praxbind (idarucizumab), humanized IgG1 Fab fragment capable of binding the anticoagulant drug dabigatran, produced in CHO cells

Boehringer Ingelheim (Rhein, Germany, & Ridgefield, CT, USA)

Rapid reversal agent for the anticoagulant drug dabigatran

2015 (EU & US)

Repatha (evolocumab), human IgG2 capable of binding human PCSK-9, produced in CHO cells

Amgen Europe Amgen (Thousand Oaks, CA, USA)

Hypercholesterolemia and mixed dyslipidemia

2015 (EU & US)

Unituxin (dinutuximab), chimeric IgG1 targeting human disialoganglioside (GD2), produced in Sp2/0 cells

United 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 cells

Eli Lilly Nederland (Utrecht, the Netherlands) Eli Lilly (Indianapolis)

Gastric cancer

2014 (EU & US)

Entyvio (vedolizumab), humanized IgG targeting the human α4β7 integrin, produced in CHO cells

Takeda Pharmaceuticals (Deerfield, IL, USA) Takeda Pharma (Taastrup, Denmark)

Ulcerative colitis, Crohn's disease

2014 (EU & US)

Gazyva in US, Gazyvaro in EU (obinutuzumab), humanized, glycoengineered mAb specific for B-cell antigen CD20, produced in CHO cells

Roche/GenentechRoche (Welwyn Garden City, UK)

CLL

2014 (EU) 2013 (US)

Sylvant (siltuximab), chimeric mAb that binds human IL-6, produced in CHO cells

Janssen Biotech

Multicentric Castleman disease

2014 (EU & US)

Kadcyla (trastuzumab emtansine), humanized mAb specific for HER2 antigen, produced in CHO cells and conjugated to the small molecule cytotoxin DM1

Roche (Welwyn Garden City, UK)

Breast cancer

2013 (EU & US)

Simponi Aria (golimumab). Active substance same as that in Simponi (see below); different strength and mode of administration

Janssen Biotech

Rheumatoid arthritis

2013 (US)

Perjeta (pertuzumab), human mAb specific for HER2, produced in CHO cells

Roche/Genentech

Breast cancer

2013 (EU)

2012 (US)

Abthrax (raxibacumab), human IgG mAb against the protective antigen (PA) of B. anthracis, produced in NS0 cells

GSK/Human Genome Sciences (Rockville, MD, USA)

Inhalational anthrax

2012 (US)

Adcetris (brentuximab vedotin), chimeric mAb conjugate specific for human CD30 (expressed on the surface of lymphoma cells), produced in CHO cells

Takeda Pharma (Roskilde, Denmark)

Seattle Genetics

Lymphoma

2012 (EU)

2011 (US)

Benlysta (belimumab), human mAb that targets human B-lymphocyte stimulator (BLyS), a B cell survival factor. produced in NS0 cells

Human Genome Sciences Glaxo Group (Greenford, UK)

Lupus

2011 (EU & US)

Xgeva (denosumab) (see Prolia)

Amgen Europe

Bone loss associated with cancer

2011 (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 cells

Bristol-Myers Squibb (Uxbridge, UK)

Melanoma

2011 (EU & US)

Actemra in US, RoActemra in EU (tocilizumab), humanized mAb specific for IL-6, produced in a mammalian cell line

Roche (Welwyn Garden City, UK)

Rheumatoid arthritis

2010 (US)

2009 (EU)

Arzerra (ofatumumab), human mAb specific for CD20, produced in NS0 hybridoma cells

Novartis (East Hanover, NJ, USA), Genmab (Greenford, UK)

CLL

2010 (EU)

2009 (US)

Prolia (denosumab), human mAb specific for receptor activator of nuclear factor κB ligand (RANKL), produced in CHO cells

Amgen Europe

Osteoporosis in postmenopausal women

2010 (EU & US)

Scintimun (besilesomab), murine mAb against nonspecific cross-reacting antigen-95 (found on surface of granulocytes), produced in hybridoma cells

CIS Bio International (Gif-sur-Yvette, France)

In vivo diagnosis or investigation of sites of inflammation or infection via scintigraphic imaging

2010 (EU)

Cimzia (certolizumab pegol), anti-TNF-α humanized and PEGylated antibody Fab fragment, produced in E. coli

UCB Pharma (Brussels, Belgium)

Crohn's disease, rheumatoid arthritis

2009 (EU)

2008 (US)

Ilaris (canakinumab), human mAb specific for IL-1β, produced in Sp2/0 cells

Novartis 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 cells

Neovii Biotech (Gräfelfing, Germany)

Malignant ascites in patients with carcinomas expressing epithelial cell adhesion molecule

2009 (EU)

Withdrawn 2017

Simponi (golimumab), human mAb specific for TNF-α, produced in Sp2/0 cells

Janssen Biologics (Leiden, the Netherlands) Janssen Biotech (Horsham, PA, USA)

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

2009 (EU & US)

Stelara (ustekinumab), human MAb specific for the p40 subunit of IL-12 and IL-23, produced in Sp2/0 cells

Janssen-Cilag

Moderate to severe plaque psoriasis

2009 (EU & US)

Lucentis (ranibizumab), humanized IgG fragment that binds and inactivates VEGF-A, produced in E. coli

Roche/Genentech

Neovascular (wet) age-related macular degeneration

2007 (EU)

2006 (US)

Soliris (eculizumab), humanized IgG that binds human C5 complement protein, produced in a murine myeloma cell line

Alexion Pharmaceuticals (Cheshire, CT, USA, & Paris)

Paroxysmal nocturnal hemoglobinuria

2007 (EU & US)

Vectibix (panitumumab), human mAb that binds to human EGF receptor, produced in CHO cells

Amgen Europe Abgenix

EGF receptor–expressing colorectal carcinoma

2007 (EU)

2006 (US)

Tysabri (natalizumab), humanized mAb against selected leukocyte integrins, produced in murine myeloma cells

Biogen Inc. (Cambridge, MA, USA) Biogen Netherlands (Badhoevedorp, the Netherlands)

Relapsing forms of multiple sclerosis

2006 (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 cells

Roche/Genentech

Moderate to severe persistent asthma in adults and adolescents

2005 (EU)

2003 (US)

Zevalin (ibritumomab tiuxetan), murine mAb against the CD20 antigen, produced in CHO cells

Spectrum Pharmaceuticals (Amsterdam)

Non-Hodgkin lymphoma

2004 (EU)

2002 (US)

Erbitux (cetuximab), chimeric mAb against human EGF receptor, produced in Sp2/0 cells

Merck KGaA (Darmstadt, Germany) Eli Lilly (Indianapolis)

EGF receptor–expressing metastatic colorectal cancer

2004 (EU & US)

Raptiva (efalizumab), humanized mAb that binds to LFA-1, which is expressed on all leukocytes; produced in CHO cells

Serono (London, UK) Genentech

Chronic moderate to severe plaque psoriasis in adults

2004 (EU)

2003 (US)

Withdrawn 2009

Avastin (bevacizumab), humanized mAb against VEGF, produced in CHO cells

Roche/Genentech (Welwyn Garden City, UK)

Metastatic colorectal cancer, glioblastoma, metastatic renal carcinoma

2005 (EU)

2004 (US)

NeutroSpec (fanolesomab), murine mAb against CD15, a surface antigen of selected leukocytes, produced in hybridoma cells

Palatin Technologies (Cranbury, NJ, USA), Mallinckrodt Pharmaceuticals (Hazelwood, MO, USA)

Imaging of equivocal appendicitis

2004 (US)

Withdrawn 2005

Humira in EU & US, Trudexa in EU (adalimumab), anti-TNF human mAb, produced in CHO cells

AbbVie (Maidenhead, UK)

Rheumatoid arthritis

2003 (EU)

2002 (US)

Trudexa withdrawn 2007 (EU)

Bexxar (tositumomab), radiolabeled mAb against CD20, produced in murine hybridoma cells

GSK

CD20-positive follicular non-Hodgkin lymphoma

2003 (US)

Withdrawn 2014

Mabcampath (EU) or Campath (US) (alemtuzumab), humanized mAb against CD52, a surface antigen of B lymphocytes, produced in CHO cells

Genzyme (Naarden, the Netherlands) Millennium (Cambridge, MA, USA)

CLL

2001 (EU & US)

Withdrawn (EU) 2012

Herceptin (trastuzumab), humanized mAb against HER2, produced in a murine cell line

Roche (Welwyn Garden City, UK)

Treatment of metastatic breast cancer overexpressing HER2 protein

2000 (EU)

1998 (US)

Remicade (infliximab), chimeric mAb against TNF-α, produced in Sp2/0 cells

Janssen (Leiden, the Netherlands)

Crohn's disease

1999 (EU)

1998 (US)

Synagis (palivizumab) humanized mAb directed against an epitope on the surface of respiratory syncytial virus, produced in a murine myeloma cell line

MedImmune (Gaithersburg, MD, USA) AbbVie Deutschland (Ludwigshafen, Germany)

Prophylaxis of lower respiratory tract disease caused by syncytial virus in children

1999 (EU)

1998 (US)

Zenapax (daclizumab), humanized mAb against the IL-2 receptor α-chain, produced in NS0 cells

Roche (Welwyn Garden City, UK) Biogen (Cambridge, MA, USA)

Prevention of acute kidney transplant rejection

1999 (EU)

1997 (US)

Withdrawn 2009 (EU)

Humaspect (votumumab), human mAb against cytokeratin tumor-associated antigen, produced in a human lymphoblastoid cell line

KS Biomedix (Farnham, UK)

Detection of carcinoma of the colon or rectum

1998 (EU)

Withdrawn 2004

MabThera in EU, Rituxan in US (rituximab), chimeric mAb against CD20 surface antigen of B lymphocytes, produced in CHO cells

Roche (Welwyn Garden City, UK)

Non-Hodgkin lymphoma

1998 (EU)

1997 (US)

Simulect (basiliximab), chimeric mAb directed against the α-chain of the IL-2 receptor, produced in a murine myeloma cell line

Novartis (Horsham, UK)

Prophylaxis of acute organ rejection in allogeneic renal transplantation

1998 (EU)

LeukoScan (sulesomab), murine mAb Fab fragment against granulocyte surface nonspecific cross-reacting antigen-90, produced in Sp2/0 cells

Immunomedics (Darmstadt, Germany)

Diagnostic imaging for infection and inflammation in bone of patients with osteomyelitis

1997 (EU)

Withdrawn 2018

Verluma (nofetumomab), murine mAb Fab fragment directed against carcinoma-associated antigen, produced in a murine cell line

Boehringer Ingelheim, NeoRx (Seattle)

Detection of small-cell lung cancer

1996 (US)

Withdrawn 1999

Tecnemab KI (antimelanoma Mab fragments), murine mAb fragments (Fab/Fab₂ mix) against HMW-MAA, produced in murine ascites culture

Amersham Sorin (Milan)

Diagnosis of cutaneous melanoma lesions

1996 (EU)

Withdrawn 2000

ProstaScint (capromab pentetate), murine mAb against the tumor surface antigen PSMA, produced in a murine cell line

EUSA Pharma USA (Langhorne, PA, USA)

Detection, staging and follow-up of prostate adenocarcinoma

1996 (US)

MyoScint (imiciromab pentetate), murine mAb fragment directed against human cardiac myosin, produced in a murine cell line

Centocor

Myocardial infarction imaging

1996 (US)

Withdrawn 1999

CEA-scan (arcitumomab), murine mAb Fab fragment against human carcinoembryonic antigen (CEA), produced in mouse ascites

Immunomedics

Detection of recurrent or metastatic colorectal cancer

1996 (EU & US)

Withdrawn 2005 (EU & US)

Indimacis 125 (igovomab), murine mAb Fab₂ fragment against the tumor-associated antigen CA125, produced in a murine cell line

CIS Bio (Gif-sur-Yvette, France)

Diagnosis of ovarian adenocarcinoma

1996 (EU)

Withdrawn 2009

ReoPro (abciximab), Fab fragments derived from a chimeric mAb against the platelet surface receptor GPII_b/III, produced in a mammalian cell line

Janssen Biologics (Leiden, the Netherlands), Centocor

Prevention of blood clots

1994 (US)

OncoScint CR/OV (satumomab pendetide), murine mAb against the tumor-associated glycoprotein TAG-72, produced in a murine cell line

Cytogen (Princeton, NJ, USA)

Detection, staging and follow-up of colorectal and ovarian cancers

1992 (US)

Withdrawn 2002

Orthoclone OKT3 (muromomab CD3), murine mAb against the T-lymphocyte surface antigen CD3, produced in a murine cell line

Centocor Ortho Biotech Products (Raritan, NJ, USA)

Reversal of acute kidney transplant rejection

1986 (US)

Opgenra (eptotermin alfa), rh BMP-7, produced in CHO cells

Olympus Biotech (Limerick, Ireland)

Posterolateral lumbar spinal fusion

2009 (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 fracture

2004 (US)

Inductos (dibotermin alfa), rh BMP-2, produced in CHO cells

Medtronic BioPharma (Heerlen, the Netherlands) Wyeth EuropaGenetics Institute

Acute tibia fractures

2002 (EU)

Infuse (rh BMP2), produced in CHO cells

Medtronic Sofamor Danek (Memphis, TN, USA)

Promotes fusion of lower spine vertebrae

2002 (US)

OP-1 implant in US, Osigraft in EU (eptotermin alfa), rh BMP-7, produced in CHO cells

Olympus Biotech (Limerick, Ireland) Stryker Biotech (Hopkinton, MA, USA)

Non-union of tibia

2001 (EU & US)

Withdrawn 2015 (EU)

Palynziq (pegvaliase-pqpz), r phenylalanine ammonia lyase, produced in E. coli and PEGylated

BioMarin (Novato, CA, USA)

Phenylketonuria

2018 (US)

Lamzede (velmanase alfa), rh α-mannosidase, expressed in precursor form in CHO cells

Chiesi Farmaceutici (Parma, Italy

α-mannosidosis

2018 (EU)

Brineura (cerliponase alfa), rh serine tripeptidyl peptidase-1, expresses in proenzyme form in CHO cells

BioMarin (Cork, Ireland), BioMarin

CLN2 disease (tripeptidyl peptidase-1 deficiency)

2017 (EU & US)

Mepsevii (vestronidase alfa-vjbk), r human lysosomal β-glucuronidase, produced in CHO cells

Ultragenyx Pharmaceutical (Novato, CA, USA)

Mucopolysaccharidosis VII

2017 (US)

Oncaspar (pegaspargase), r asparaginase, produced in E. coli and conjugated to monomethoxypropylene glycol

Baxalta Innovations

Lymphoblastic leukemia, lymphoma

2016 (EU)

Spectrila (asparaginase), r asparaginase, produced in E. coli

Medac Gesellschaft für klinische Spezialpräparate (Wedel, Germany)

Lymphoblastic leukemia, lymphoma

2016 (EU)

Kanuma (sebelipase alfa), rh lysosomal acid lipase, produced in the eggs of transgenic chickens

Alexion Europe (Rueil-Malmaison, France) Alexion Pharmaceuticals (Cheshire, CT, USA)

Enzyme replacement therapy in patients with lysosomal acid lipase deficiency

2015 (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 cells

Alexion Europe (Rueil-Malmaison, France) Alexion (Cheshire, CT, USA)

Enzyme replacement therapy in patients with pediatric-onset hypophosphatasia

2015 (EU & US)

Vimizim (elosulfase alfa), rh N-acetlygalactosamine-6-sulfatase, produced in CHO cells

BioMarin (London, UK)

Mucopolysaccharidosis IVA (Morquio A syndrome)

2014 (EU & US)

Krystexxal (pegloticase), r urate oxidase, PEGylated after synthesis, produced in E. coli

Savient Pharma Ireland (Dublin) Crealta Pharmaceuticals (Lake Forest, IL, USA)

Gout

2013 (EU)

2010 (US)

Withdrawn 2016 (EU)

Elelyso (taliglucerase alfa), rh glucocerebrosidase, produced in engineered carrot root cell culture

Pfizer (New York), Protalix BioTherapeutics (Karmiel, Israel)

Gaucher disease

2012 (US)

Voraxaze (glucarpidase), r carboxypeptidase, produced in E. coli

BTG International (West Conshohocken, PA, USA)

Toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function

2012 (US)

Lumizyme (alglucosidase alfa), rh acid-α-glucosidase, produced in CHO cells

Sanofi Genzyme

Pompe disease (glycogen storage disease type II)

2010 (US)

VPRIV (velaglucerase alfa), rh glucocerebrosidase, produced in a human fibroblast cell line

Shire Human Genetic Therapies (Danderyd, Sweden)

Gaucher disease

2010 (EU & US)

Elaprase (idursulfase), rh iduronate-2-sulfatase, produced in a human cell line

Shire Human Genetic Therapies

Mucopolysaccharidosis II (Hunter syndrome)

2007 (EU)

2006 (US)

Naglazyme (galsulfase), rh N-acetylgalactosamine-4-sulfatase, produced in CHO cells

BioMarin (London & Novato, CA, USA)

Long-term enzyme replacement therapy in mucopolysaccharidosis VI

2006 (EU)

2005 (US)

Myozyme (algulcosidase alfa), rh acid glucosidase, produced in CHO cells

Sanofi Genzyme (Naarden, the Netherlands)

Pompe disease

2006 (EU & US)

Aldurazyme (laronidase), r α-l-iduronidase, produced in CHO cells

BioMarin

Long-term replacement in mucopolysaccharidosis I

2003 (EU & US)

Hylenex (hyaluronidase), rh hyaluronidase, produced in CHO cells

Halozyme Therapeutics (San Diego)

Adjuvant to increase absorption and dispersion of other drugs

2005 (US)

Fabrazyme (agalsidase beta), rh α-galactosidase, produced in CHO cells

Sanofi 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 line

Shire Human Genetic Therapies, TKT Europe

Fabry disease (α-galactosidase A deficiency)

2001 (EU)

Fasturtec in EU, Elitex in US (rasburicase), r urate oxidase, produced in S. cerevisiae

Sanofi (Paris)

Hyperuricemia

2002 (US)

2001 (EU)

Cerezyme (imiglucerase), rh β-glucocerebrosidase, produced in CHO cells

Genzyme (Naarden, the Netherlands)

Gaucher disease

1997 (EU)

1994 (US)

Pulmozyme (dornase alpha), r DNase, produced in CHO cells

Roche/Genentech

Cystic fibrosis

1993 (US)

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 Enbrel

Sandoz (Kundl, Austria, & Princeton, NJ, USA)

Rheumatoid arthritis, selected other inflammatory diseases

2017 (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 diseases

2017 (EU)

Benepali (etanercept), rh TNF receptor–IgG Fc fusion protein, produced in CHO cells, biosimilar to Enbrel

Samsung Bioepis (Chertsey, UK)

Arthritis, psoriasis, axial spondyloarthritis

2016 (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 cancer

2013 (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 degeneration

2012 (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 cells

Bristol-Myers Squibb (Uxbridge, UK)

Prophylaxis of organ rejection following kidney transplant

2011 (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 cells

Regeneron 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. coli

Amgen Europe

Thrombocytopenia

2009 (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 line

Bristol-Myers Squibb (Uxbridge, UK)

Rheumatoid arthritis

2007 (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 cells

Astellas Pharma (Deerfield, IL, USA)

Moderate to severe chronic plaque psoriasis in adults

2003 (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 arthritis

2000 (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. coli

Eisai (Tokyo), Ligand Pharmaceuticals (San Diego)

Cutaneous T-cell lymphoma

1999 (US)

Tegsedi (inotersen), a 20-nucleotide single-stranded oligonucleotide manufactured by direct chemical synthesis

Ionis USA (London)

Hereditary transthyretin amyloidosis

2018 (EU)

Luxturna (voretigene neparvovec-rzyl), a live, nonreplicating adeno-associated virus genetically modified to express the human RPE65 gene

Spark Therapeutics (Philadelphia)

Retinal dystrophy

2017 (US)

Spinraza (nusinersen sodium), an 18-nucleotide antisense oligonucleotide manufactured by direct chemical synthesis

Biogen Idec (Maidenhead, UK) Biogen (Cambridge, MA, USA)

Spinal muscular atrophy

2017 (EU) 2016 (US)

Exondys 51 (eteplirsen), a chemically synthesized antisense oligonucleotide

Sarepta Therapeutics (Cambridge, MA, USA)

Duchenne muscular dystrophy

2016 (US)

Imlygic (talimogene laherparepvec), an engineered herpes simplex virus type 1 capable of producing GM-CSF

Amgen EuropeAmgen

Melanoma

2015 (EU & US)

Kynamro (mipomersen sodium), a chemically synthesized antisense oligonucleotide

Kastle Therapeutics (Chicago)

Familial hypercholesterolemia

2013 (US)

Glybera (alipogene tiparvovec), human LPL gene housed in an engineered AAV1 vector

uniQure (Amsterdam)

Lipoprotein lipase deficiency

2012 (EU)

Withdrawn 2017

Macugen (pegaptanib sodium injection), a synthetic PEGylated oligonucleotide that specifically binds VEGF

Pfizer, PharmaSwiss Ceska Republika (Prague) Eyetech (Palm Beach Gardens, FL, USA),

Neovascular, age-related macular degeneration

2006 (EU)

2004 (US)

Vitravene (fomivirsen), an antisense oligonucleotide

Novartis Ophthalmics Europe (Farnborough, UK) Isis Pharmaceuticals (Carlsbad, California)

Cytomegalovirus retinitis in AIDS patients

1999 (EU)

1998 (US)

Withdrawn 2002 (EU)

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 CD3ζ

Novartis (East Hanover, NJ, USA)

Acute lymphoblastic leukemia, large B-cell lymphoma

2017 (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 domains

Kite Pharma (Santa Monica, CA, USA)

Large B-cell lymphoma

2017 (US)

Strimvelis, autologous CD34⁺ cells transduced with an engineered retroviral vector encoding the human adenosine deaminase sequence

GlaxoSmithKline (Cork, Ireland)

Severe combined immunodeficiency

2016 (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 gene

MolMed (Milan)

Hematopoietic stem cell transplantation, graft-versus-host disease

2016 (EU)