Biosimilars approved in Europe

Biosimilars/General | Posted 08/07/2011 post-comment1 Post your comment

Last update: 12 February 2021

In the European Union (EU), a legal framework for approving biosimilars was established in 2003. This framework means that biosimilars can only be approved centrally via the European Medicines Agency (EMA) and not nationally.

Biosimilars V13E10

EMA first developed guidelines for the approval of biosimilars via an abbreviated registration process during 2005 to 2006, and since then EMA has developed many general and specific guidelines for biosimilars [1].

Omnitrope (somatropin) was the first product approved in the EU as a biosimilar in 2006 [2]. To date, EMA has recommended the approval of 77 biosimilars within the product classes of: 1) human growth hormone; 2) granulocyte colony-stimulating factor; 3) erythropoiesis stimulating agent; 4) insulin; 5) follicle-stimulating hormone (FSH); 6) parathyroid hormone; 7) tumour necrosis factor (TNF)-inhibitor; and 8) monoclonal antibodies for use in the EU, see Table 1.

Table 1: EU approved biosimilars*
Product name Active substance Therapeutic area Authorization date Manufacturer/ Company name
Abasaglar (previously Abasria) insulin glargine Diabetes 9 Sep 2014 Eli Lilly/Boehringer
Ingelheim
Abseamed epoetin alfa Anaemia
Cancer
Chronic kidney failure
27 Aug 2007 Medice Arzneimittel Pütter
Accofil filgrastim Neutropenia 17 Sep 2014 Accord Healthcare
Amgevita adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile rheumatoid arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative colitis
21 Mar 2017  Amgen
Amsparity  adalimumab Ankylosing spondylitis
Hidradenitis Suppurativa
Crohn’s disease
Juvenile rheumatoid arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
13 Feb 2020 Pfizer
Aybintio bevacizumab Breast neoplasms
Colorectal neoplasms
Fallopian tube neoplasms
Non-small-cell lung carcinoma
Ovarian neoplasms
Peritoneal neoplasms
Renal cell carcinoma
Uterine cervical neoplasms
19 Aug 2020 Samsung Bioepis
Bemfola follitropin alfa Anovulation (IVF) 26 Mar 2014 Finox Biotech
Benepali etanercept Axial spondyloarthritis
Psoriatic arthritis
Plaque psoriasis
Rheumatoid arthritis 
13 Jan 2016 Samsung Bioepis
Binocrit epoetin alfa Anaemia
Chronic kidney failure
28 Aug 2007 Sandoz
Blitzima rituximab Non-Hodgkin lymphoma
Chronic B-cell lymphocytic leukaemia
13 Jul 2017 Celltrion
Cegfila (previously Pegfilgrastim Mundipharma) pegfilgrastim Neutropenia 19 Dec 2019 Mundipharma Biologics
Enoxaparin BECAT enoxaparin sodium Venous thromboembolism 24 Mar 2017 Laboratorios ROVI
Epoetin alfa Hexal epoetin alfa Anaemia
Cancer
Chronic kidney failure
27 Aug 2007 Hexal
Equidacent bevacizumab Breast neoplasms
Colorectal neoplasms
Non-small-cell lung carcinoma
Ovarian neoplasms
Renal cell carcinoma
24 Sep 2020 Centus Biotherapeutics
Erelzi etanercept Ankylosing spondylitis
Juvenile rheumatoid arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
23 Jun 2017 Sandoz
Filgrastim Hexal filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
6 Feb 2009 Hexal
Flixabi infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
26 May 2016 Samsung Bioepis
Fulphila pegfilgrastim Neutropenia 20 Nov 2018 Mylan
Grastofil filgrastim Neutropenia 17 Oct 2013 Apotex
Grasustek  pegfilgrastim Neutropenia 20 Jun 2019 Juta Pharma (USV)
Halimatoz adalimumab Ankylosing spondylitis
Hidradenitis suppurativa
Juvenile rheumatoid arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Uveitis
26 Jul 2018 Sandoz
Hefiya adalimumab Ankylosing spondylitis
Hidradenitis suppurativa
Juvenile rheumatoid arthritis
Psoriasis
Uveitis
26 Jul 2018 Sandoz
Herzuma trastuzumab Early breast cancer
Metastatic breast cancer
Metastatic gastric cancer
8 Feb 2018 Celltrion Healthcare
Hulio adalimumab Ankylosing spondylitis
Crohn’s Disease
Hidradenitis suppurativa
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative Colitis
Uveitis
16 Sep 2018 Mylan/Fujifilm Kyowa Kirin Biologics
Hyrimoz adalimumab Ankylosing spondylitis
Crohn’s Disease
Hidradenitis suppurativa
Juvenile rheumatoid arthritis
Papulosquamous skin disease
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative Colitis
Uveitis
26 Jul 2018 Sandoz
Idacio adalimumab Ankylosing spondylitis
Arthritis
Crohn’s Disease
Hidradenitis suppurativa
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
24 Apr 2019 Fresenius Kabi
Imraldi adalimumab Ankylosing spondylitis
Arthritis
Crohn’s Disease
Hidradenitis suppurativa
Psoriatic arthritis,
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
24 Aug 2017 Samsung Bioepis
Inflectra infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
10 Sep 2013 Hospira
Inhixa enoxaparin sodium Venous thromboembolism 15 Sep 2016 Techdow Europe
Insulin aspart Sanofi insulin aspart Diabetes mellitus 25 Jun 2020 Sanofi-Aventis
Insulin lispro Sanofi insulin lispro Diabetes mellitus 18 Jul 2017 Sanofi-Aventis
Kanjinti trastuzumab Early breast cancer
Metastatic breast cancer
Metastatic gastric cancer
16 May 2018 Amgen/Allergan
Kixelle insulin aspart Diabetes mellitus CHMP positive opinion 10 Dec 2020 Mylan
Livogiva teriparatide Osteoporosis 27 Aug 2020 Theramex Ireland
Movymia teriparatide Osteoporosis 11 Jan 2017 Stada Arzneimittel
Mvasi bevacizumab Breast neoplasms Fallopian tube neoplasms
Non-small-cell lung carcinoma
Ovarian neoplasms
Peritoneal neoplasms
Renal cell carcinoma
15 Jan 2018 Amgen
Nepexto etanercept Ankylosing spondylitis
Juvenile rheumatoid arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Spondylarthropathies
25 May 2020 Mylan
Nivestim filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
7 Jun 2010 Hospira (Pfizer)
Nyvepria pegfilgrastim Neutropenia 18 Nov 2020 Pfizer
Ogivri trastuzumab Early breast cancer
Metastatic breast cancer
Metastatic gastric cancer
12 Dec 2018 Biocon/Mylan
Omnitrope somatropin Pituitary dwarfism
Prader-Willi syndrome
Turner syndrome
12 Apr 2006 Sandoz
Onbevzi bevacizumab Breast neoplasms Colorectal neoplasms
Fallopian tube neoplasms
Non-small-cell lung carcinoma
Ovarian neoplasms
Peritoneal neoplasms
Renal cell carcinoma
Uterine Cervical Neoplasms
CHMP positive opinion 21 Nov 2020 Samsung Bioepis
Ontruzant trastuzumab Early breast cancer
Metastatic breast cancer
Metastatic gastric cancer
15 Nov 2017 Samsung Bioepis
Ovaleap follitropin alfa Anovulation (IVF) 27 Sep 2013 Teva Pharma
Pelgraz pegfilgrastim Neutropenia 20 Sep 2018 Accord Healthcare
Pelmeg  pegfilgrastim Neutropenia 20 Nov 2018 Cinfa Biotech/ Mundipharma
Qutavina teriparatide Osteoporosis 27 Aug 2020 EuroGenerics Holdings
Ratiograstim filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
15 Sep 2008 Ratiopharm
Remsima infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
10 Sep 2013 Celltrion
Retacrit epoetin zeta Anaemia
Autologous blood transfusion
Cancer
Chronic kidney failure
18 Dec 2007 Hospira
Ritemvia rituximab Wegener granulomatosis
Microscopic polyangiitis
Non-Hodgkin Lymphoma
13 Jul 2017 Celltrion
Rixathon rituximab Chronic B-cell lymphocytic leukaemia
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Rheumatoid arthritis
Wegener granulomatosis
15 Jun 2017 Sandoz
Riximyo rituximab Chronic B-cell lymphocytic leukaemia
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Rheumatoid arthritis
Wegener granulomatosis
15 Jun 2017 Sandoz
Ruxience rituximab Chronic lymphocytic leukaemia
Granulomatosis with polyangiitis
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Rheumatoid arthritis
Pemphigus vulgaris
1 Apr 2020 Pfizer
Semglee insulin glargine Diabetes 28 Mar 2018 Mylan
Silapo epoetin alfa Anaemia
Autologous blood transfusion
Cancer
Chronic kidney failure
18 Dec 2007 Stada Arzneimittel
Solymbic adalimumab Ankylosing spondylitis
Crohn’s disease
Hidradenitis suppurativa
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative colitis
22 Mar 2017 Amgen
Terrosa teriparatide Osteoporosis 4 Jan 2017 Gedeon Richter
Tevagrastim filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
15 Sep 2008 Teva Generics
Thorinane enoxaparin sodium Venous thromboembolism 14 Sep 2016 Pharmathen
Trazimera trastuzumab Stomach Neoplasms
Breast Neoplasms
26 Jul 2018 Pfizer
Truxima rituximab Chronic lymphocytic leukaemia
Granulomatosis with polyangiitis
Microscopic polyangiitis
Non-Hodgkin’s lymphoma
Rheumatoid arthritis
17 Feb 2017 Celltrion
Udenyca pegfilgrastim Neutropenia 21 Sep 2018 ERA Consulting (Coherus Biosciences)
Yuflyma adalimumab Axial spondyoarthritis
Crohn’s Disease
Juvenile idiopathic arthritis
Hidradenitis suppurativa
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
CHMP positive opinion 10 Dec 2020 Celltrion Healthcare
Zarzio filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
6 Feb 2009 Sandoz
Zercepac trastuzumab "Stomach Neoplasms
Breast Neoplasms"
27 Jul 2020 Accord Healthcare
Zessly infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
psoriasis
Rheumatoid arthritis
Ulcerative colitis
18 May 2018 Sandoz
Ziextenzo  pegfilgrastim Neutropenia 22 Nov 2018 Sandoz
Zirabev bevacizumab Breast neoplasms
Colorectal neoplasms
Non-small-cell lung carcinoma
Renal cell carcinoma
Uterine cervical neoplasms
14 Feb 2019 Pfizer
*Data updated on 12 February 2021.
CHMP: Committee for Medicinal Products for Human Use; IVF: in vitro fertilization.
Source: EMA.

  
Eight biosimilar approvals have been withdrawn after approval, see Table 2:
• two for filgrastim biosimilars: Filgrastim ratiopharm in April 2011 and CT Arzneimittel’s Biograstim in December 2016
• one for somatropin biosimilars: Biopartner’s Valtropin in May 2012 and Somatropin Biopartners in November 2017
• one for an insulin glargine biosimilar: Merck’s Lusduna in October 2018
• two for adalimumab biosimilars: Boehringer Ingelheim’s Cyltezo in January 2019 and Fresenius Kabi’s Kromeya in December 2019
• one for a rituximab biosimilar: Celltrion’s Rituzena in April 2019

Two biosimilar were withdrawn before approval: Reliance GeneMedix’s epoetin alfa biosimilar, Epostim; and Mabion’s rituximab biosimilar, see Table 2.

Two biosimilar applications were refused by the agency, see Table 2: an interferon alfa-2a biosimilar, Alpheon, from Biopartners, and a human insulin biosimilar, Solumarv, from Marvel Lifesciences.

This leaves a total of 69 biosimilars approved for use in Europe.

Table 2: EMA refused/withdrawn biosimilars*
Product name Active substance Therapeutic area Authorization date Manufacturer/ Company name
Alpheon interferon alfa-2a Chronic hepatitis C Refused 5 Sep 2006 BioPartners
Biograstim filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
15 Sep 2008 
Withdrawn on 22 Dec 2016
CT Arzneimittel
Cyltezo adalimumab Crohn’s disease
Hidradenitis suppurativa
Juvenile idiopathic arthritis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
10 Nov 2017
Withdrawn on 15 Jan 2019
Boehringer Ingelheim
Epostim epoetin alfa anaemia Withdrawn on 15 Mar 2011 Reliance GeneMedix 
Filgrastim ratiopharm filgrastim Cancer
Haematopoietic stem cell transplantation
Neutropenia
15 Sep 2008
Withdrawn 20 Apr 2011 
Ratiopharm
Kromeya adalimumab Ankylosing spondylitis
Arthritis
Crohn’s Disease
Hidradenitis suppurativa
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
Uveitis
2 Apr 2019
Withdrawn on 17 Dec 2019
Fresenius Kabi
Lusduna insulin glargine Diabetes 3 Jan 2017
Withdrawn on 29 Oct 2018
Merck (MSD)
Mabion CD20 rituximab - Withdrawn on 16 April 2020 Mabion
Rituzena (previously Tuxella) rituximab Wegener granulomatosis
Microscopic polyangiitis
Non-Hodgkin Lymphoma
Chronic B-cell lymphocytic leukaemia
13 Jul 2017
Withdrawn on 10 Apr 2019
Celltrion
Solumarv insulin human Diabetes Refused 11 Feb 2016 Marvel Lifesciences
Somatropin Biopartners somatropin Pituitary dwarfism
Turner syndrome
9 Sep 2013
Withdrawn on 9 Nov 2017 
BioPartners
Valtropin somatropin Pituitary dwarfism
Turner syndrome
24 Apr 2006
Withdrawn on 14 Aug 2012 
BioPartners
*Data updated on 12 February 2021.
Source: EMA.

  
The positive opinion reached by the EMA’s Committee for Medicinal Products for Human Use (CHMP) on 26 July 2014 for the insulin glargine biosimilar Abasaglar (previously Abasria) came as a relief to diabetes sufferers in Europe, after the disappointing withdrawal of the applications for three biosimilar insulin products by Marvel LifeSciences in November 2012 [3].The positive opinion reached by the EMA’s Committee for Medicinal Products for Human Use (CHMP) on 27 June 2013 for the infliximab biosimilars Inflectra and Remsima was a landmark decision, proving that the biosimilar concept can be successfully applied to such complex molecules as monoclonal antibodies.

Related articles
Remsima approved in Colombia

EMA approves first monoclonal antibody biosimilar

Biosimilar monoclonal antibody approved in Korea

References
1.  GaBI Online - Generics and Biosimilars Initiative. EU guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jul 4]. Available from: www.gabionline.net/Guidelines/EU-guidelines-for-biosimilars
2.  GaBI Online - Generics and Biosimilars Initiative. Biosimilars use in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jul 4]. Available from: www.gabionline.net/Reports/Biosimilars-use-in-Europe
3. GaBI Online - Generics and Biosimilars Initiative. Marvel withdraws biosimilar insulin applications [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jul 4]. Available from: www.gabionline.net/Biosimilars/News/Marvel-withdraws-biosimilar-insulin-applications

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Source: EMA

comment icon Comments (1)
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Posted 20/09/2021 by Alexis Vaujany
Comment on updates

It seems that Thorinane's MA was withdrawn in 2019 because it has not been marketed in the European Union in the three years following the granting of the authorisation.

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