Biosimilars of adalimumab Posted 03/10/2014

Last update: 15 November 2019

Adalimumab is a human monoclonal antibody that treats autoimmune diseases by inhibiting tumour necrosis factor (TNF); a soluble inflammatory cytokine. Adalimumab binds to TNF-alpha (TNF-α), preventing it from activating TNF receptors, which cause the inflammatory reactions associated with autoimmune diseases. Adalimumab is indicated for the treatment of rheumatoid, juvenile idiopathic and psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and ulcerative colitis.

The originator product, AbbVie’s Humira (adalimumab), was approved by the US Food and Drug Administration (FDA) in December 2002 and by the European Medicines Agency (EMA) in September 2003 [1]. Humira had worldwide sales of US$18.4 billion in 2017 and accounted for approximately 65% of AbbVie’s total net revenues in 2017.

The patents on Humira expired in Europe in June 2017 [1]. However, in the US AbbVie has stated that although the composition of matter patent covering Humira expired in December 2016, non-composition of matter patents covering Humira expire no earlier than 2022. The company has therefore made settlement agreements with Amgen and Samsung Bioepis delaying the launch of biosimilars in the US until January 2023 [2, 3]. Some of the adalimumab biosimilars approved or in development are presented in Table 1.

Table 1: Biosimilars and non-originator biologicals* of adalimumab approved or in development

Company name, Country

Product name

Stage of development

Adello Biologics

-

Preclinical

AET BioTech/BioXpress Therapeutics, Germany/Switzerland

-

Biosimilar in pipeline. Development partnership announced in November 2012 [4]

Alvotech, Iceland

AVT02

Phase III trial started in March 2019

Amgen, USA

Amjevita (US)/ Amgevita (EU)/ Solymbic (EU)
(ABP 501)

Approved by FDA in September 2016 [5] and by EC in March 2017 [6]. Launched in EU in October 2018 [7]

BIOCND, South Korea

BCD100

Phase I trial ongoing. Marketing approval expected by 2023

Baxalta (now part of Shire), USA

BAX 923

Phase III confirmatory trial ongoing

Biocad, Russia

BCD-057

Phase III results reported in March 2019 [8]

Bio-Thera Solutions, China*

BAT1406

Submitted to NMPA in August 2018 [9]

Boehringer Ingelheim, Germany

Cyltezo (BI 695501)

Approved by FDA in August 2017 [5]. Approved by EC in November 2018 [6]. Announced that it will only pursue biosimilars in the US in November 2018 [10]

Celltrion, South Korea

CT-P17

Phase III trial started in March 2019 [5]

CinnaGen, Iran*

CinnoRA

Phase III trial in RA completed in January 2017 [14]

Coherus Biosciences, USA

CHS-1420

Pharmacokinetic study completed in August 2014 [15]. Ongoing phase III trial met primary endpoint demonstrating similarity in January 2017 [16]

Fresenius Kabi, Germany [Bought from Merck KGaA (Merck Group) in [14]

Idacio/Kromeya (MSB11022)

Approved by EC in April 2019 [6]

Fujifilm/Kyowa Hakko Kirin (Fujifilm Kyowa Kirin Biologics), )/Mylan [15], Japan/USA

Hulio (FKB327)

50:50 joint venture announced in March 2012.  Approved by EC in September 2018 [6]. Launched in EU in October 2018

Hetero Drugs, India*

Mabura

''Similar biologic’ launched in India in January 2018 [16]

Hisun Pharmaceuticals, China*

-

Submitted to NMPA in August 2018 [9]

Innovent Biologics, China*

IBI-303

Phase III clinical trial ongoing in China in April 2017. Submitted to NMPA in November 2018 [17]

LG Life Sciences/Mochida Pharmaceutical, South Korea/Japan

LBAL

Phase I trial expected to be completed in March 2015. Under phase III development in January 2018

mAbxience, Spain

-

In pipeline

Momenta Pharmaceuticals, USA

M923

Positive results from phase III trial reported in November 2016 [18]

Neuclone, Australia

-

Preclinical

Outlook Therapeutics (Oncobiologics)/Viropro, USA

ONS-3010

Phase III trial ongoing in November 2019

Pfizer, USA

PF-06410293

Phase III trial in RA completed in December 2017

PlantForm, Canada

-

Clinical trials in humans began in 2014. Launch, in partnership with a pharmaceutical company, in world markets expected in 2016 [19]

Prestige Biopharma, Singapore

PBP1502

In phase I development

Samsung Bioepis (Biogen/Samsung)/ Merck , South Korea/USA

mraldi (EU)/Hadlima (Australia/Korea) (SB5)

Imraldi approved by EC in August 2017 [6]. Hadlima approved by Korea’s MFDS in September 2017 [20], by Australia’s TGA in January 2018 [21] and by Health Canada in May 2018 [22]. Launched in Europe in October 2018 [7]

Sandoz, Switzerland

Halimatoz (EU)/ Hefiya (EU)/ Hyrimoz (EU/ US) (GP2017)

Approved by EC in July 2018 [6] and by FDA in October 2018 [5]

Shanghai Henlius Biotech (Fosun Pharma), China*

HLX03

Phase I trial in RA in China completed in November 2018. Phase III trial in psoriasis initiated in October 2017

Shanghai Junshi Biosciences 

UBP1211

Submitted to NMPA in November 2018 [23]

Torrent Pharmaceuticals, India*

Adfrar

Similar biologic’ launched in India in January 2016 [16]

Zydus Cadila, India*

Exemptia 
(ZRC3197)

Similar biologic’ launched in India in December 2014 [16]

EC: European Commission; EMA: European Medicines Agency; EU: European Union; FDA: US Food and Drug Administration; MFDS: Ministry of Food and Drug Safety; PK: pharmacokinetic; RA: rheumatoid arthritis.
*See editor’s comment

FDA approved Amgen’s adalimumab biosimilar in September 2016 [5], and Europe approved Amgevita in March 2017 [6]. In August 2017, Samsung Bioepis received EC approval for Imraldi and in November 2018 Boehringer Ingelheim received EC approval for Cyltezo [6]. Then in April 2019, Fresenius Kabi received European approval for Idacio [6].

Indian generics maker Zydus Cadila launched its similar biologic in India in December 2014 under the brand name Exemptia (adalimumab) [16]. At the time, the company claimed that it was ‘the first company anywhere in the world to launch a biosimilar of adalimumab’.

Editor’s comment
It should be noted that ‘similar biologics’ approved in India, ‘biogenerics’ approved in Iran, copy biologicals approved in China, and ‘medicamento biológico similares’ approved in Argentina might not have been authorized following as strict a regulatory process as is required for approval of biosimilars in the European Union. The EMA (European Medicines Agency) regulatory requirements ensure the same high standards of quality, safety and efficacy for biosimilars as for originator biologicals, and also include a rigorous comparability exercise with the reference product.

Related articles
Biosimilars of ranibizumab

Biosimilars of rituximab

Biosimilars of infliximab

Biosimilars of trastuzumab

Biosimilars of cetuximab

Biosimilars of bevacizumab

References
1. Derbyshire M. Patent expiry dates for biologicals: 2018 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;8(1):24-31. doi:10.5639/gabij.2019.0801.003 
2. GaBI Online - Generics and Biosimilars Initiative. Amgen’s adalimumab biosimilar will only be launched in US in 2023 [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29] Available from: www.gabionline.net/Biosimilars/News/Amgen-s-adalimumab-biosimilar-will-only-be-launched-in-US-in-2023
3. GaBI Online - Generics and Biosimilars Initiative. AbbVie and Samsung Bioepis reach patent deal over Humira biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29] Available from: www.gabionline.net/Biosimilars/General/AbbVie-and-Samsung-Bioepis-reach-patent-deal-over-Humira-biosimilar
4. GaBI Online - Generics and Biosimilars Initiative. The latest biosimilars agreements [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/News/The-latest-biosimilars-agreements
5. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US
6. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
7. GaBI Online - Generics and Biosimilars Initiative. Adalimumab biosimilars Amgevita and Imraldi launched in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-biosimilars-Amgevita-and-Imraldi-launched-in-Europe
8. GaBI Online - Generics and Biosimilars Initiative. Biocad advancing its non-originator biologicals in Russia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Biocad-advancing-its-non-originator-biologicals-in-Russia
9. GaBI Online - Generics and Biosimilars Initiative. Adalimumab copy biologicals accepted for review in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-copy-biologicals-accepted-for-review-in-China
10. GaBI Online - Generics and Biosimilars Initiative. Boehringer Ingelheim and Sandoz abandon biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Boehringer-Ingelheim-and-Sandoz-abandon-biosimilars
11. GaBI Online - Generics and Biosimilars Initiative. MENA region biologicals maker CinnaGen received EU GMP certification [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Pharma-News/MENA-region-biologicals-maker-CinnaGen-received-EU-GMP-certification
12. GaBI Online - Generics and Biosimilars Initiative. Adalimumab biosimilar has comparable pharmacokinetics to Humira [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Feb 20]. Available from: www.gabionline.net/Biosimilars/Research/Adalimumab-biosimilar-has-comparable-pharmacokinetics-to-Humira
13. GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for adalimumab biosimilar from Coherus [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 21]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-adalimumab-biosimilar-from-Coherus
14. GaBI Online - Generics and Biosimilars Initiative. Fresenius Kabi acquires Merck KGaA’s biosimilars business [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Pharma-News/Fresenius-Kabi-acquires-Merck-KGaA-s-biosimilars-business
15. GaBI Online - Generics and Biosimilars Initiative. Mylan partners with Fujifilm Kyowa Kirin Biologics to commercialize adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Pharma-News/Mylan-and-Fujifilm-Kyowa-Kirin-Biologics-partner-on-adalimumab-biosimilar
16. GaBI Online - Generics and Biosimilars Initiative. ‘Similar biologics’ approved and marketed in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India
17. GaBI Online - Generics and Biosimilars Initiative. Another adalimumab copy biological accepted for review in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/News/Another-adalimumab-copy-biological-accepted-for-review-in-China
18. GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for adalimumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 21]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-adalimumab-and-trastuzumab-biosimilars
19. GaBI Online - Generics and Biosimilars Initiative. Biosimilar trastuzumab made in tobacco plants [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Aug 12]. Available from: www.gabionline.net/Biosimilars/News/Biosimilar-trastuzumab-made-in-tobacco-plants
20. GaBI Online - Generics and Biosimilars Initiative. Adalimumab and trastuzumab biosimilars approved in South Korea [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-and-trastuzumab-biosimilars-approved-in-South-Korea
21. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Australia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Australia
22. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Canada
23. GaBI Online - Generics and Biosimilars Initiative. Adalimumab copy biological accepted for review in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 15]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-copy-biologicals-accepted-for-review-in-China

Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.

Copyright – Unless otherwise stated all contents of this website are © 2016 Pro Pharma Communications International. All Rights Reserved.

Source: EMA, ClinicalTrials.gov, US FDA

Comments (1)

Biosimilars of adalimumab/ Zydus Cadila posted 19/12/2014 - by Sandeep

Zydus Cadila launched a biosimilar for this drug in India in Dec 2014. Should that not be added to this page?