Biosimilars of adalimumab

Biosimilars/General | Posted 03/10/2014 post-comment1 Post your comment

Last update: 29 January 2021

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.

Adalimumab V13F21

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. Approved by Colombia's INVIMA in April 2020 [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
Bio-Thera Solutions, China* Qletli ('BAT1406) Approved by China's NMPA in November 2019
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.
Celltrion, South Korea CT-P17 Phase III trial started in March 2019
CinnaGen, Iran* CinnoRA Phase III trial in RA completed in January 2017
Coherus Biosciences, USA CHS-1420 Pharmacokinetic study completed in August 2014. Ongoing phase III trial met primary endpoint demonstrating similarity in January 2017.
Fresenius Kabi, Germany [Bought from Merck KGaA (Merck Group) 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. Approved by Japan's PMDA in June 2020 [9] and by FDA in July 2020 [7].
Hetero Drugs, India* Mabura 'Similar biologic’ launched in India in January 2018 [10]
Hisun Pharmaceuticals, China* - Submitted to China's NMPA in August 2018
Innovent Biologics, China* Sulinno (IBI-303) Approved by China's NMPA in September 2020 [11]
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
Neuclone, Australia - Preclinical
Outlook Therapeutics (Oncobiologics)/Viropro, USA ONS-3010 Phase III trial ongoing in November 2019
Pfizer, USA Abrilada (US)/ Amsparity (EU) (PF-06410293) Approved by FDA in April 2019 [5] and by EMA in December 2019 [6]
PlantForm, Canada - Clinical trials in humans began in 2014. Launch, in partnership with a pharmaceutical company, in world markets expected in 2016.
Prestige Biopharma, Singapore PBP1502 In phase I development
Samsung Bioepis (Biogen/Samsung)/Merck, South Korea/USA Imraldi (EU)/ Hadlima (Australia/ Korea) (SB5) Imraldi approved by EC in August 2017 [6]. Hadlima approved by Korea’s MFDS in September 2017, by Australia’s TGA in January 2018, by Health Canada in May 2018 and by FDA in July 2019 [5]. Launched in Europe in October 2018.
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 China's NMPA in November 2018
Torrent Pharmaceuticals, India* Adfrar 'Similar biologic’ launched in India in January 2016 [10]
Zydus Cadila, India* Exemptia 
(ZRC3197)
'Similar biologic’ launched in India in December 2014 [12]
Cadalimab 'Similar biologic’ launched in India in August 2020 [12]
EC: European Commission; EMA: European Medicines Agency; EU: European Union; FDA: US Food and Drug Administration; INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos; MFDS: Ministry of Food and Drug Safety; NMPA: National Medical Products Administration; PK: pharmacokinetic; PMDA: Pharmaceuticals and Medical Devices Agency; RA: rheumatoid arthritis.
*See editor’s comment

FDA approved Amgen’s adalimumab biosimilar in September 2016 [5], and Europe and Colombia’s INVIMA approved Amgevita in March 2017 and in April 2020, respectively [6, 7]. In August 2017, Samsung Bioepis received EC approval for Imraldi and in November 2018 Boehringer Ingelheim received EC approval for Cyltezo [6]. In April 2019, Fresenius Kabi received European approval for Idacio [6].  FDA approved Pfizer’s Abrilada and Samsung Bioepis’ Hadlima in April and July 2019, respectively [5]. Pfizer also gained EMA approval for its adalimumab biosimilar Amsparity in December 2019 [6].

Fujifilm Kyowa Kirin Biologics and Mylan gained EC approval for Hulio (FKB327) in September 2018, Mylan launched the product in Europe in October 2018. Japan’s PMDA and US FDA approved Hulio in June and July 2020, respectively. Fujifilm Kyowa Kirin Biologics is a joint venture set up by Fujifilm and biotech firm Kyowa Hakko Kirin back in 2011. The company is the marketing authorization holder in Japan, but US-based drugmaker Mylan is in charge of commercialization. The two made a deal back in April 2018 allowing Mylan to commercialize its adalimumab biosimilar FKB327. Mylan also has exclusive rights to commercialize FKB327 in Europe.

Innovent Biologics gained approval for Sulinno (IBI-303) from China’s NMPA in September 2020 [11].

Indian generics maker Zydus Cadila launched its similar biologic in India in December 2014 under the brand name Exemptia (adalimumab) [10]. At the time, the company claimed that it was ‘the first company anywhere in the world to launch a biosimilar of adalimumab’. Zydus Cadila also launched another adalimumab similar biologic in India Cadalimab in August 2020 [12]. 

Editor’s comment
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 but they are not universally accepted by regulatory bodies outside of the European Union (EU). It should be noted that ‘copy biologicals’ approved in China, ‘similar biologics’ approved in India and ‘biogenerics’ approved in Iran might not have been authorized if they had been subjected to the strict regulatory processes required for approval of biosimilars in the EU.

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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. Amgevita approved in Colombia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 29]. Available from: www.gabionline.net/Biosimilars/News/Amgevita-approved-in-Colombia 
8. GaBI Online - Generics and Biosimilars Initiative. Bio-Thera gains Chinese approval for adalimumab copy biological and starts ustekinumab trial [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 29]. Available from: www.gabionline.net/Biosimilars/News/Bio-Thera-gains-Chinese-approval-for-adalimumab-copy-biological-and-starts-ustekinumab-trial 
9. GaBI Online - Generics and Biosimilars Initiative. Japanese approval for first adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 29]. Available from: www.gabionline.net/Biosimilars/News/Japanese-approval-for-first-adalimumab-biosimilar 
10. 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 
11. GaBI Online - Generics and Biosimilars Initiative. China approves adalimumab copy biological Sulinno [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 29]. Available from: www.gabionline.net/Biosimilars/News/China-approves-adalimumab-copy-biological-Sulinno 
12. GaBI Online - Generics and Biosimilars Initiative. Cadila launches two new similar biologics in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 29]. Available from: www.gabionline.net/Biosimilars/News/Cadila-launches-two-new-similar-biologics-in-India 

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Source: EMA, ClinicalTrials.gov, US FDA

comment icon Comments (1)
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Posted 19/12/2014 by Sandeep
Biosimilars of adalimumab/ Zydus Cadila

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

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