Home / Biosimilars / General / Biosimilars of adalimumab

Biosimilars of adalimumab Posted 03/10/2014

Last update: 29 June 2018

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 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]

Amgen, USA

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

Approved by FDA in September 2016 [5] and by EMA in January 2017 [6]

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

Boehringer Ingelheim, Germany

Cyltezo (BI 695501)

Phase I trials in Belgium and New Zealand completed in 2012 and 2015 [7, 8]. Positive results from phase III trials reported in October 2016, June 2017 and July 2017 [9-11]. Approved by FDA in August 2017 [12]. Approved by EMA in September 2017 [13].

Celltrion, South Korea

CT-P17

In pipeline

CinnaGen, Iran*

CinnoRA

Phase III trial in RA completed 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 2017] [17] 

MSB11022

Phase III trial started in March 2016. Expected to be completed in September 2017 [18]

Fujifilm/Kyowa Hakko Kirin (Fujifilm Kyowa Kirin Biologics), )/Mylan [19], Japan/USA

FKB327

50:50 joint venture announced in March 2012. Positive results from phase III trial reported in October 2016. Submitted to EMA in May 2017 [20]

Hetero Drugs, India*

Mabura

''Similar biologic’ launched in India in January 2018 [21]

LG Life Sciences/Mochida Pharmaceutical, South Korea/Japan

LBAL

Phase I trial expected to be completed in March 2015 [22]. Under phase III development (January 2018) 

mAbxience, Spain

-

In pipeline

Momenta Pharmaceuticals, USA

M923

Phase III trial started in October 2015 [23]. Momenta was collaborating with Baxter on six biosimilars [24]. Adalimumab collaboration ended in September 2016 [25]. Positive results from phase III trial reported in November 2016 [26].

Neuclone, Australia

-

Preclinical [27]

Oncobiologics/Viropro, USA

ONS-3010

Phase I PK study completed in February 2015 [28]. One of six monoclonal antibody biosimilars for which the companies are collaborating [29].  Phase III trial expected to start in 2018.

Pfizer, USA

PF-06410293

Phase I trial expected to be completed in January 2014 [30]. Phase III trial in RA ongoing.

PlantForm, Canada

-

Clinical trials in humans began in 2014. Launch, in partnership with a pharmaceutical company, in world markets expected in 2016 [31]

Prestige Biopharma

PBP1502

In phase I development

Samsung Bioepis (Biogen/Samsung)/ Merck [32], South Korea/USA

Imraldi (EU)/Hadlima (Korea) (SB5)

Phase I trial completed. Phase III trial expected to be completed in May 2015 [33]. Imraldi approved by EMA on 23 June 2016 [34]. Hadlima approved by Korea’s MFDS on 22 September 2017 [35].

Sandoz, Switzerland

GP2017

Started phase III trial in December 2013 [36], expected to be completed in April 2016. Positive data from phase III trial in psoriasis reported in March 2017. Approved by EMA in June 2018 [37] and submitted to FDA in January 2018 [38].

Torrent Pharmaceuticals, India*

Adfrar

Similar biologic’ launched in India in January 2016 [39]

Zydus Cadila, India*

Exemptia 
(ZRC3197)

Similar biologic’ launched in India in December 2014 [40]

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

There appear to be several front runners in the race to biosimilar adalimumab in Europe/the US. Momenta Pharmaceuticals (Momenta) and generics maker Sandoz have both completed phase III trials with their candidates [23, 36]. But leading the race are biotech major Amgen and Samsung Bioepis (a Biogen and Samsung joint venture). FDA approved Amgen’s biosimilar adalimumab in September 2016 [5], and EMA approved Imraldi, which is made by Samsung Bioepis, in June 2016 [34]. Boehringer Ingelheim received approval for its Cyltezo from FDA and EMA in August and September 2017, respectively [12, 13].

Indian generics maker Zydus Cadila launched its similar biologic in India in December 2014 under the brand name Exemptia (adalimumab). At the time, the company claimed that it was ‘the first company anywhere in the world to launch a biosimilar of adalimumab’ [40].

Editor’s comment
It should be noted that ‘similar biologics’ approved in India, ‘biogenerics’ approved in Iran 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: 2017 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(1):29-34. doi:10.5639/gabij.2018.0701.007
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. FDA approval for Amgen’s adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Sep 30]. Available from: www.gabionline.net/Biosimilars/News/FDA-approval-for-Amgen-s-adalimumab-biosimilar 
6. GaBI Online - Generics and Biosimilars Initiative. EMA approval for adalimumab biosimilars Amgevita and Solymbic [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Biosimilars/News/EMA-approval-for-adalimumab-biosimilars-Amgevita-and-Solymbic
7.   GaBI Online - Generics and Biosimilars Initiative. Development of biosimilars for rheumatology [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/Research/Development-of-biosimilars-for-rheumatology
8.   GaBI Online - Generics and Biosimilars Initiative. Positive phase I results for adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Apr 8]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-I-results-for-adalimumab-biosimilar
9.   GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for Boehringer’s adalimumab biosimilar [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-Boehringer-s-adalimumab-biosimilar
10.   GaBI Online - Generics and Biosimilars Initiative. Boehringer’s adalimumab biosimilar ‘equivalent’ to Humira [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Biosimilars/Research/Boehringer-Ingelheim-s-adalimumab-biosimilar-equivalent-to-Humira
11.   GaBI Online - Generics and Biosimilars Initiative. Boehringer Ingelheim starts phase III interchangeability trial for adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Biosimilars/News/Boehringer-Ingelheim-starts-phase-III-interchangeability-trial-for-adalimumab-biosimilar
12.  GaBI Online - Generics and Biosimilars Initiative. FDA approves adalimumab biosimilar Cyltezo [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-adalimumab-biosimilar-Cyltezo
13.  GaBI Online - Generics and Biosimilars Initiative. EMA approval for adalimumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from:www.gabionline.net/Biosimilars/News/EMA-approval-for-adalimumab-and-trastuzumab-biosimilars
14.  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
15.  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
16.  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
17.  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
18.  GaBI Online - Generics and Biosimilars Initiative. Merck Group starts phase III trial for adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Sep 15]. Available from: www.gabionline.net/Biosimilars/News/Merck-Group-starts-phase-III-trial-for-adalimumab-biosimilar
19.  GaBI Online - Generics and Biosimilars Initiative. Mylan and Fujifilm Kyowa Kirin Biologics partner on 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
20.  GaBI Online - Generics and Biosimilars Initiative. EMA accepts application for adalimumab biosimilar from Fujifilm Kyowa Kirin Biologics [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 15]. Available from: www.gabionline.net/Biosimilars/News/EMA-accepts-application-for-adalimumab-biosimilar-from-Fujifilm-Kyowa-Kirin-Biologics
21.  GaBI Online - Generics and Biosimilars Initiative. Hetero launches adalimumab similar biologic in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Biosimilars/News/Hetero-launches-adalimumab-similar-biologic-in-India
22.  GaBI Online - Generics and Biosimilars Initiative. LG Life Sciences and Mochida make deal for adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Feb 20]. Available from: www.gabionline.net/Biosimilars/News/LG-Life-Sciences-and-Mochida-make-deal-for-adalimumab-biosimilar
23.  GaBI Online - Generics and Biosimilars Initiative. Baxalta and Momenta start phase III trial for adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Oct 16]. Available from: www.gabionline.net/Biosimilars/News/Baxalta-and-Momenta-start-phase-III-trial-for-adalimumab-biosimilar
24.  GaBI Online - Generics and Biosimilars Initiative. Baxter and Momenta make biosimilars deal [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/News/Baxter-and-Momenta-make-biosimilars-deal
25.  GaBI Online - Generics and Biosimilars Initiative. Baxalta and Momenta part ways on adalimumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 21]. Available from: www.gabionline.net/Biosimilars/News/Baxalta-and-Momenta-part-ways-on-adalimumab-biosimilar
26.  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
27.  GaBI Online - Generics and Biosimilars Initiative. Denosumab biosimilar being developed in Australia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Biosimilars/News/Denosumab-biosimilar-being-developed-in-Australia
28.  GaBI Online - Generics and Biosimilars Initiative. Adalimumab biosimilar meets primary endpoints in first clinical study [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jun 26]. Available from: www.gabionline.net/Biosimilars/Research/Adalimumab-biosimilar-meets-primary-endpoints-in-phase-I-study
29.  GaBI Online - Generics and Biosimilars Initiative. Oncobiologics and Viropro make biosimilar deal [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/News/Oncobiologics-and-Viropro-make-biosimilar-deal
30.  GaBI Online - Generics and Biosimilars Initiative. Pfizer to start trial for biosimilar adalimumab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/News/Pfizer-to-start-trial-for-biosimilar-adalimumab
31.  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
32.  GaBI Online - Generics and Biosimilars Initiative. Merck outlines biosimilars programme [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 21]. Available from: www.gabionline.net/Biosimilars/News/Merck-outlines-biosimilars-programme
33.  GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for Samsung Bioepis biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Apr 8]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-Samsung-Bioepis-biosimilars
34.  GaBI Online - Generics and Biosimilars Initiative. EMA approval for adalimumab biosimilar Imraldi [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 5]. Available from: www.gabionline.net/Biosimilars/News/EMA-approval-for-adalimumab-biosimilar-Imraldi
35.  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
36.  GaBI Online - Generics and Biosimilars Initiative. Sandoz starts phase III biosimilar adalimumab trial [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Oct 3]. Available from: www.gabionline.net/Biosimilars/News/Sandoz-starts-phase-III-biosimilar-adalimumab-trial
37.  GaBI Online - Generics and Biosimilars Initiative. EMA approves adalimumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Biosimilars/News/EMA-approves-adalimumab-and-trastuzumab-biosimilars
38.  GaBI Online - Generics and Biosimilars Initiative. FDA accepts applications for adalimumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jun 29]. Available from: www.gabionline.net/Biosimilars/News/FDA-accepts-applications-for-adalimumab-and-trastuzumab-biosimilars
39.  GaBI Online - Generics and Biosimilars Initiative. ‘Similar biologics’ approved and marketed in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Apr 8]. Available from: www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India
40.  GaBI Online - Generics and Biosimilars Initiative. Adalimumab similar biologic launched in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jun 26]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-similar-biologic-launched-in-India

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 PharmaCommunications International. All Rights Reserved.

http://gabionline.net/Biosimilars/News/EMA-approval-for-adalimumab-and-trastuzumab-biosimilars

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?