Biosimilars approved in Europe

Biosimilars/General | Posted 08/07/2011 2 Post your comment

Last update: 12 May 2023

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.

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 93 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: EMA approved biosimilars*

Product name	Active substance	Therapeutic area	Authorization date	Manufacturer/ Company name
Abasaglar (previously Abasria)	insulin glargine	Diabetes mellitus	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
Abevmy	bevacizumab	Breast cancer Carcinoma of the cervix Colon cancer Fallopian tube cancer Non-small-cell lung carcinoma Ovarian cancer Peritoneal cancer Renal cell cancer	21 Apr 2021	Mylan (now Viatris)
Alymsys	bevacizumab	Breast cancer Carcinoma of the cervix Colon cancer Fallopian tube cancer Non-small-cell lung carcinoma Ovarian cancer Peritoneal cancer Renal cell cancer	26 Mar 2021	mAbxience Research
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 Uvetis	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
Bekemv	eculizumab	Atypical haemolytic uraemic syndrome (aHUS) Paroxysmal nocturnal haemoglobinuria (PNH)	24 Feb 2023	Amgen
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
Byooviz	ranibizumab	Degenerative myopia Diabetic retinopathy Macular edema Wet macular degeneration	18 Aug 2021	Samsung Bioepis
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
Epysqli	eculizumab	Paroxysmal nocturnal hemoglobinuria: adult and children	CHMP positive opinion 31 Mar 2023	Samsung Bioepis
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)
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
Hukyndra	adalimumab	Ankylosing spondylitis Crohn’s Disease Hidradenitis suppurativa Psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative Colitis Uveitis	15 Nov 2021	Alvotech/Stada Artnimettel
Hulio	adalimumab	Ankylosing spondylitis Crohn’s Disease Hidradenitis suppurativa Psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative Colitis Uveitis	17 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	2 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 (Pfizer)
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
Kirsty (previously Kixelle)	insulin aspart	Diabetes mellitus	5 February 2021	Biocon/Viatris (formerly Mylan)
Libmyris	adalimumab	Ankylosing spondylitis Crohn’s Disease Hidradenitis suppurativa Psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative Colitis Uveitis	12 Nov 2021	Alvotech/Stada Artnimettel
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	11 Jan 2021	Samsung Bioepis
Ontruzant	trastuzumab	Early breast cancer Metastatic breast cancer Metastatic gastric cancer	15 Nov 2017	Samsung Bioepis
Oyavas	bevacizumab	Breast cancer Carcinoma of the cervix Colon cancer Fallopian tube cancer Non-small-cell lung carcinoma Ovarian cancer Peritoneal cancer Renal cell cancer	26 Mar 2021	Stada Arzneimittel
Ovaleap	follitropin alfa	Anovulation (IVF)	27 Sep 2013	Teva Pharma
Pelgraz	pegfilgrastim	Neutropenia	21 Sep 2018	Accord Healthcare
Pelmeg	pegfilgrastim	Neutropenia	20 Nov 2018	Cinfa Biotech/Mundipharma
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
Ranivisio	ranibizumab	Diabetes complications Diabetic retinopathy Macular edema Wet macular degeneration	25 Aug 2022	Bioeq/Teva Pharma
Retacrit	epoetin zeta	Anaemia Autologous blood transfusion Cancer Chronic kidney failure	18 Dec 2007	Hospira (Pfizer)
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 mellitus	28 Mar 2018	Biocon/Viatris (formerly Mylan)
Silapo	epoetin zeta	Anaemia Autologous blood transfusion Cancer Chronic kidney failure	18 Dec 2007	Stada Arzneimittel
Sondelbay	teriparatide	Osteoporosis	24 Mar 2022	Accord Healthcare
Stimufend	pegfilgrastim	Neutropenia	24 Mar 2022	Fresenius Kabi
Terrosa	teriparatide	Osteoporosis	4 Jan 2017	Gedeon Richter
Tevagrastim	filgrastim	Cancer Haematopoietic stem cell transplantation Neutropenia	15 Sep 2008	Teva Generics
Trazimera	trastuzumab	Stomach Neoplasms Breast Neoplasms	26 Jul 2018	Pfizer
Truvelog Mix 30	insulin aspart	Diabetes mellitus	Apr 2022	Sanofi-Aventis
Truxima	rituximab	Chronic lymphocytic leukaemia Granulomatosis with polyangiitis Microscopic polyangiitis Non-Hodgkin’s lymphoma Rheumatoid arthritis	17 Feb 2017	Celltrion Healthcare
Vegzelma	bevacizumab	Breast neoplasms Colorectal neoplasms Non-small-cell lung carcinoma Ovarian neoplasms Renal cell carcinoma	17 Aug 2022	Celltrion Healthcare
Ximluci	ranibizumab	Diabetes complications Diabetic retinopathy Macular edema Wet macular degeneration	9 Nov 2022	Stada Arzneimittel/Xbrane Biopharma
Yuflyma	adalimumab	Axial spondyoarthritis Crohn’s Disease Juvenile idiopathic arthritis Hidradenitis suppurativa Psoriatic arthritis Psoriasis Rheumatoid arthritis Ulcerative colitis Uveitis	11 Feb 2021	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 May 2023
CHMP: Committee for Medicinal Products for Human Use; IVF: in vitro fertilization.
Source: EMA

Seventeen biosimilar approvals have been withdrawn after approval, see Table 2:
• four for adalimumab biosimilars: Boehringer Ingelheim’s Cyltezo in January 2019, Amgen’s Solymbic in March 2019, Fresenius Kabi’s Kromeya in December 2019 and Sandoz’s Halimatoz in January 2021
• two for bevacizumab biosimilars: Equidacent from Centus Biotherapeutics in November 2021 and Mylan’s (now Viatris) Lextemy in December 2021
• one for an enoxaparin sodium biosimilar: Pharmathen’s Thorinane in October 2019
• two for filgrastim biosimilars: Filgrastim ratiopharm in April 2011 and CT Arzneimittel’s Biograstim in December 2016
• one for an human insulin biosimilar: Biocon’s Inpremzia in April 2023
• one for an insulin glargine biosimilar: Merck’s Lusduna in October 2018
• one for a pegfilgrastim biosimilar: ERA Consulting’s (Coherus Biosciences) Udenyca in February 2021
• two for rituximab biosimilars: Celltrion’s Rituzena in April 2019 and Celltrion’s Ritemvia in August 2021
• two for somatropin biosimilars: Biopartner’s Valtropin in May 2012 and Somatropin Biopartners in November 2017
• one for a teriparatide biosimilar: Qutavina from EuroGenerics Holdings in January 2018

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 15 Mar 2011	Reliance GeneMedix
Equidacent	bevacizumab	Breast neoplasms Colorectal neoplasms Non-small-cell lung carcinoma Ovarian neoplasms Renal cell carcinoma	24 Sep 2020 Withdrawn on 23 Nov 2021	Centus Biotherapeutics
Filgrastim ratiopharm	filgrastim	Cancer Haematopoietic stem cell transplantation Neutropenia	15 Sep 2008 Withdrawn on 20 Apr 2011	Ratiopharm
Halimatoz	adalimumab	Ankylosing spondylitis Hidradenitis suppurativa Juvenile rheumatoid arthritis Psoriatic arthritis Psoriasis Rheumatoid arthritis Uveitis	26 Jul 2018 Withdrawn on 29 Jan 2021	Sandoz
Inpremzia	insulin human	Diabetes	25 Apr 2022 Withdrawn on 20 Apr 2023
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
Lextemy	bevacizumab	Breast cancer Carcinoma of the cervix Colon cancer Fallopian tube cancer Non-small-cell lung carcinoma Ovarian cancer Peritoneal cancer Renal cell cancer	CHMP positive opinion 25 Feb 2021 Withdrawn on 14 Dec 2021	Mylan (now Viatris)
Lusduna	insulin glargine	Diabetes	3 Jan 2017 Withdrawn on 29 Oct 2018	Merck (MSD)
Qutavina	teriparatide	Osteoporosis	27 Aug 2020 Withdrawn on 18 Jan 2021	EuroGenerics Holdings
Ritemvia	rituximab	Wegener granulomatosis Microscopic polyangiitis Non-Hodgkin Lymphoma	13 Jul 2017 Withdrawn on 16 Aug 2021	Celltrion
Rituximab Mabion	rituximab	Chronic lymphocytic leukaemia Granulomatosis with polyangiitis Microscopic polyangiitis Non-Hodgkin Lymphoma	Withdrawn on 16 Mar 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
Solymbic	adalimumab	Ankylosing spondylitis Crohn’s disease Hidradenitis suppurativa Psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative colitis	22 Mar 2017 Withdrawn on 5 Mar 2019	Amgen
Somatropin Biopartners	somatropin	Pituitary dwarfism Turner syndrome	9 Sep 2013 Withdrawn on 9 Nov 2017	BioPartners
Thorinane	enoxaparin sodium	Venous thromboembolism	14 Sep 2016 Withdrawn on 24 Oct 2019	Pharmathen
Udenyca	pegfilgrastim	Neutropenia	21 Sep 2018 Withdrawn on 15 Feb 2021	ERA Consulting (Coherus Biosciences)
Valtropin	somatropin	Pituitary dwarfism Turner syndrome	24 Apr 2006 Withdrawn on 10 May 2012	BioPartners

*Data updated on 12 May 2023
Source: EMA

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: an interferon alfa-2a biosimilar, Alpheon, from Biopartners; and a human insulin biosimilar, Solumarv, from Marvel Lifesciences, see Table 2.

By end of February 2023, there is a total of 25 biosimilars withdrawn pre-approval, in the classes of: adalimumab (1); infliximab (1); insulin (6); pegfilgrastim (6, 2 resubmitted); teriparatide (2); trastuzumab (4), including one each of epoetin and rituximab mentioned above.

This leaves a total of 76 biosimilars approved for use in Europe.

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

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

Comments (2)

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Posted 07/01/2022 by Anthika U, GaBI Online Editorial Office

Response to ‘Thorinane MA’ of Biosimilars approved in Europe

Dear Alexis Vaujany,
Thank you for your valuable comment received on 20/9/2021. We have updated the article tables of ‘Biosimilars approved in Europe’ with the correct information.
We very much appreciate your kind feedback. Thank you for your interest in GaBI, and please continue with your valuable comments to GaBI Online.
Best Regards, Anthika

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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