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Biosimilars of trastuzumab Posted 19/09/2014

Last update: 29 September 2017

Trastuzumab is a monoclonal antibody that interferes with the human epidermal growth factor receptor 2 (HER2)/neu receptor. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably. Trastuzumab is therefore used to treat certain breast cancers.

The originator product, Roche’s Herceptin (trastuzumab), was approved by the US Food and Drug Administration (FDA) in September 1998 and by the European Medicines Agency (EMA) in August 2000 [1]. Herceptin had 2016 worldwide sales of CHF 6.8 billion (US$6.7 billion).

The patents on Herceptin will expire in the US in June 2019 and expired in Europe in July 2014 [1]. Just some of the trastuzumab biosimilars approved or in development are presented below, see Table 1.

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

Company name, Country

Product name

Stage of development

Actavis (Allergan)/Amgen/Synthon, USA/The Netherlands

ABP 980

Phase III trial expected to be completed in December 2016 [2]. Positive phase III results reported in July 2016 [3] and in September 2017 [4]. Submitted to EMA for approval in March 2017 [5] and to FDA in July 2017 [6]

Alteogen/Cristalia, South Korea/Brazil*

-

Phase I

Apotex (Apobiologix), Canada

-

In pipeline

Biocad, Russia*

HERtiCAD
(BCD-022)

Phase III trial expected to be completed in November 2014 [7]. Non-originator biological approved in Russia in January 2016 [8]

Biocon/Mylan, India*/USA

CanMab/ Hertraz

‘Similar biologic’ approved in India in October 2013 [9]

Hercules
(MYL-1401O)

Phase III trial in metastatic breast cancer expected to be completed in December 2018 [10]. Positive data reported in June 2016 [11]. Submitted to EMA for approval in August 2016 [12]. Submitted to FDA for approval in November 2016 [13]. FDA’s ODAC to review at meeting on 13 July 2017 [14]. Withdrawn from EMA August 2017 [15]. FDA’s target action date extended until 3 December 2017 [15]

BioXpress Therapeutics, Switzerland

-

In pipeline

Celltrion /Teva Pharmaceuticals Industries, South Korea/ Israel

Herzuma
(CT-P6) 

Marketed in South Korea following approval in January 2014 [16]. Phase III trial started in EEA in April 2014 [17]. Collaborating with Teva in US and Canada [18]. Submitted to EMA for approval in November 2016 [19]. Submitted to Japan’s MHLW for approval in April 2017 [20]. Submitted to FDA in July 2017 [6]

EirGenix, Taiwan

EG12014

Positive data from phase I bioequivalence trial reported in May 2017

Hanwha Chemical, South Korea

HD201

Phase I trial in Europe as of 2013

Oncobiologics/Viropro, USA

ONS-1050

Biosimilar in development; one of six monoclonal antibody biosimilars for which the companies are collaborating [21]. Phase I trial expected to start in 2018

Pfizer/Hospira, USA

PF-05280014

Phase I study completed [22]. Phase III study ongoing, expected to be completed March 2018 [23]. Positive phase III results reported in November 2016 [24] and September 2017 [25]. Submitted to EMA and to FDA for approval in September 2017 [25]

PlantForm, Canada

-

Clinical trials in humans expected to begin in 2014. Launch, in partnership with a pharmaceutical company, in world markets expected in 2016 [26]

Prestige Biopharma

HD201

Phase I trial in EU completed in 2014 and Phase III trial ongoing.

Samsung Bioepis (Biogen/Samsung)/Merck [27], South Korea/USA

Ontruzant (SB3)

Phase III trial in early breast cancer expected to be completed May 2016 [10]. Approved by EMA in September 2017 [28]

Shanghai CP Guojian Pharmaceutical, China*

Saiputing

Approved by CFDA in June 2014

Shanghai Henlius Biotech

HLX02

Approved by CFDA. Phase III trial started in March 2017

Stada Arzneimittel/Gedeon Richter, Germany/Hungary

-

Collaborating on biosimilars of trastuzumab and infliximab [29]. Richter signed technology transfer and in-licensing agreement with DM Bio in October 2016 [30]

CFDA: China Food and Drug Administration; EEA: European Economic Area, this area includes the 28 European Union Member States, plus Iceland, Liechtenstein and Norway; EMA: European Medicines Agency; EU: European Union; FDA: US Food and Drug Administration; MHLW: Ministry of Health, Labour and Welfare; ODAC: Oncologic Drugs Advisory Committee

*See editor’s comment

Celltrion received approval for its trastuzumab biosimilar, Herzuma, from the Korean Ministry of Food and Drug Safety (MFDS) in January 2014 [16]. The company submitted a marketing application to EMA in November 2016 for approval of its trastuzumab biosimilar Herzuma (CT-P6) in Europe [19]. It submitted a marketing application to FDA in July 2017 [6].

Samsung Bioepis, a joint venture between South Korean electronics giant Samsung and biotechnology company Biogen, received marketing approval from the EMA in September 2017 [28].

Actavis/Amgen, Biocon/Mylan and Pfizer have submitted marketing applications to EMA for approval of their trastuzumab biosimilars in Europe [5,12,26]. Biocon/Mylan withdrew their application from the EMA as part of ‘procedural requirements’ after implementation of corrective and preventive actions and re-inspection of Biocon’s ‘Drug Product facility’ in Bangalore were required before a good manufacturing practice (GMP) compliance certificate would be issued for the site. The companies expect to re-submit their application by the end of September 2017 [15].

Actavis/Amgen, Biocon/Mylan and Pfizer have also submitted marketing applications to FDA for approval of their trastuzumab biosimilars in the US [6,13,26]

Editor’s comment
It should be noted that ‘similar biologics’ approved in India, ‘copy biologicals’ approved in China, follow-on biological products approved in Brazil and 'non-originator biologicals' approved in Russia might not have been authorized following as strict a regulatory process as is required for approval of biosimilars in the EU. 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.

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References
1. Derbyshire M. Patent expiry dates for biologicals: 2016 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2017;6(1):27-30. doi:10.5639/gabij.2017.0601.006
2. GaBI Online - Generics and Biosimilars Initiative. Amgen, Hospira and Sandoz set to dominate US biosimilars market [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Reports/Amgen-Hospira-and-Sandoz-set-to-dominate-US-biosimilars-market
3. GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for Amgen’s trastuzumab 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-Amgen-s-trastuzumab-biosimilar
4. GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for Amgen’s trastuzumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 29]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-Amgen-s-trastuzumab-biosimilar2
5. GaBI Online - Generics and Biosimilars Initiative. Amgen submits trastuzumab biosimilar to EMA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 21]. Available from: www.gabionline.net/Biosimilars/News/Amgen-submits-trastuzumab-biosimilar-to-EMA
6. GaBI Online - Generics and Biosimilars Initiative. Two trastuzumab biosimilars submitted to FDA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 29]. Available from: www.gabionline.net/Biosimilars/News/Two-trastuzumab-biosimilars-submitted-to-FDA
7. GaBI Online - Generics and Biosimilars Initiative. Amgen and Pfizer seek deal with Russian biosimilars firm [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Pharma-News/Amgen-and-Pfizer-seek-deal-with-Russian-biosimilars-firm
8. GaBI Online - Generics and Biosimilars Initiative. Trastuzumab non-originator biological approved in Russia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Apr 8]. Available from: www.gabionline.net/Biosimilars/News/Trastuzumab-non-originator-biological-approved-in-Russia
9.   GaBI Online - Generics and Biosimilars Initiative. ‘Similar biologics’ approved and marketed in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India
10. GaBI Online - Generics and Biosimilars Initiative. Pivotal clinical trials for trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Aug 12]. Available from: www.gabionline.net/Biosimilars/Reports/Pivotal-clinical-trials-for-trastuzumab-biosimilars
11. GaBI Online - Generics and Biosimilars Initiative. Mylan presents comparability data for trastuzumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Aug 12]. Available from: www.gabionline.net/Biosimilars/Research/Mylan-presents-comparability-data-for-trastuzumab-biosimilar
12. GaBI Online - Generics and Biosimilars Initiative. Mylan and Biocon submit trastuzumab biosimilar to EMA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Biosimilars/News/Mylan-and-Biocon-submit-trastuzumab-biosimilar-to-EMA
13. GaBI Online - Generics and Biosimilars Initiative. Mylan and Biocon submit trastuzumab biosimilar to FDA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Biosimilars/News/Mylan-and-Biocon-submit-trastuzumab-biosimilar-to-FDA
14. GaBI Online - Generics and Biosimilars Initiative. FDA advisory committee to review bevacizumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jul 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-advisory-committee-to-review-bevacizumab-and-trastuzumab-biosimilars
15. GaBI Online - Generics and Biosimilars Initiative. Biocon withdraws EU applications for trastuzumab and pegfilgrastim biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 29]. Available from: www.gabionline.net/Biosimilars/General/Biocon-withdraws-EU-applications-for-trastuzumab-and-pegfilgrastim-biosimilars
16. GaBI Online - Generics and Biosimilars Initiative. Biosimilar trastuzumab approved in Korea [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/News/Biosimilar-trastuzumab-approved-in-Korea
17. GaBI Online - Generics and Biosimilars Initiative. Celltrion starts phase III biosimilar trastuzumab trial [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Aug 12]. Available from: www.gabionline.net/Biosimilars/News/Celltrion-starts-phase-III-biosimilar-trastuzumab-trial
18. GaBI Online - Generics and Biosimilars Initiative. Teva and Celltrion to partner on biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Biosimilars/News/Teva-and-Celltrion-to-partner-on-biosimilars
19. GaBI Online - Generics and Biosimilars Initiative. Celltrion submits trastuzumab biosimilar application to EMA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Biosimilars/News/Celltrion-submits-trastuzumab-biosimilar-application-to-EMA
20. GaBI Online - Generics and Biosimilars Initiative. Celltrion making progress with biosimilars in China and Japan [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jul 14]. Available from: www.gabionline.net/Biosimilars/News/Celltrion-making-progress-with-biosimilars-in-China-and-Japan
21. GaBI Online - Generics and Biosimilars Initiative. Oncobiologics and Viropro make biosimilar deal [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/News/Oncobiologics-and-Viropro-make-biosimilar-deal
22. GaBI Online - Generics and Biosimilars Initiative. Robust data for biosimilar trastuzumab programmes presented [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/Research/Robust-data-for-biosimilar-trastuzumab-programmes-presented
23. GaBI Online - Generics and Biosimilars Initiative. Pfizer to start phase III biosimilar trastuzumab trial [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Jun 19]. Available from: www.gabionline.net/Biosimilars/News/Pfizer-to-start-phase-III-biosimilar-trastuzumab-trial
24. 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 Jan 6]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-adalimumab-and-trastuzumab-biosimilars
25. GaBI Online - Generics and Biosimilars Initiative. Positive phase III results for Pfizer’s trastuzumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 29]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-Pfizer-s-trastuzumab-biosimilar
26.   GaBI Online - Generics and Biosimilars Initiative. Biosimilar trastuzumab made in tobacco plants [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/News/Biosimilar-trastuzumab-made-in-tobacco-plants
27. GaBI Online - Generics and Biosimilars Initiative. Merck outlines biosimilars programme [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Biosimilars/News/Merck-outlines-biosimilars-programme
28. GaBI Online - Generics and Biosimilars Initiative. EMA approval for adalimumab and trastuzumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Sep 29]. Available from: www.gabionline.net/Biosimilars/News/EMA-approval-for-adalimumab-and-trastuzumab-biosimilars
29.  GaBI Online - Generics and Biosimilars Initiative. Stada and Richter to collaborate on biosimilar development [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 19]. Available from: www.gabionline.net/Biosimilars/News/Stada-and-Richter-to-collaborate-on-biosimilar-development
30. GaBI Online - Generics and Biosimilars Initiative. Richter and DM Bio make deal for trastuzumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 6]. Available from: www.gabionline.net/Pharma-News/Richter-and-DM-Bio-make-deal-for-trastuzumab-biosimilar

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Source: EMA, US FDA

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