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Biosimilars of trastuzumab Posted 19/09/2014

Last update: 6 July 2018

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 2017 worldwide sales of CHF 7.0 billion (US$7.5 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

Kanjinti (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]. Approved by EMA in March 2018 [5]. Submitted to FDA for approval in July 2017 [6]. Rejected by FDA in June 2018 [7]

Alteogen/Cristalia, South Korea/Brazil*

-

Phase I

Apotex (Apobiologix), Canada

-

In pipeline

AryoGen Pharmed, Iran*

AryoTrust

Approved by Iran’s FDO

Biocad, Russia*

HERtiCAD
(BCD-022)

Phase III trial in HER2+ breast cancer completed in October 2016 [8]. Non-originator biological approved in Russia in January 2016 [9]

Biocon/Mylan, India*/USA

CanMab/ Hertraz

‘Similar biologic’ approved in India in October 2013 [10].

Hercules / Ogivri (US)
(MYL-1401O)

Zedora

Phase III trial in metastatic breast cancer expected to be completed in December 2018 [11]. Positive data reported in June 2016 [12]. Submitted to EMA for approval in August 2016 [13]. Submitted to FDA for approval in November 2016 [14]. FDA’s ODAC to review at meeting on 13 July 2017 [15]. Withdrawn from EMA August 2017 [16]. FDA’s target action date extended until 3 December 2017 [17]
Re-submitted to EMA for approval in December 2017 [18]. Approved by FDA in December 2017 [19]
Approved by Brazil’s ANVISA in December 2017 [20]

BioXpress Therapeutics, Switzerland

-

In pipeline

Celltrion /Teva Pharmaceuticals Industries, South Korea/ Israel

Herzuma
(CT-P6) 

Marketed in South Korea following approval in January 2014 [21]. Phase III trial started in EEA in April 2014 [22]. Collaborating with Teva in US and Canada [23]. Approved by EC in February 2018 [24]. Submitted to Japan’s MHLW for approval in April 2017 [25]. Submitted to FDA in July 2017 [6]. Rejected by FDA in April 2018 [26]. Resubmitted to FDA in May 2018 [27]

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 [28]. Phase I trial expected to start in 2018

Pfizer/Hospira, USA

Trazimera (PF‑05280014)

Phase I study completed [29]. Phase III study ongoing, expected to be completed March 2018 [30]. Positive phase III results reported in November 2016 [31] and September 2017 [32]. Submitted to EMA and to FDA for approval in September 2017 [32]. Rejected by FDA in April 2018 [33]. Approved by EMA in June 2018 [34]

PlantForm, Canada

-

Clinical trials in humans expected to begin in 2014. Launch, in partnership with a pharmaceutical company, in world markets expected in 2016 [35]

Prestige Biopharma, Singapore

HD201

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

Samsung Bioepis (Biogen/Samsung)/ Daewoong Pharmaceutical/ Merck (MSD) [36], South Korea/USA

Ontruzant (EU)/ Samfenet (Korea) (SB3)

Phase III trial in early breast cancer expected to be completed May 2016 [11]. Approved in Europe in November 2017 [37]. Approved by Korea’s MFDS on 9 November 2017 [38]. Submitted to FDA for approval in December 2017 [39]

Shanghai CP Guojian Pharmaceutical, China*

Saiputing

Approved by CFDA in June 2014

Shanghai Henlius Biotech, China*

HLX02

Approved by CFDA. Phase III trial started in March 2017

Stada Arzneimittel/Gedeon Richter, Germany/Hungary

-

Collaborating on biosimilars of trastuzumab and infliximab [40]. Richter signed technology transfer and in-licensing agreement with DM Bio in October 2016 [41]

EEA: European Economic Area, this area includes the 28 European Union member states, plus Iceland, Liechtenstein and Norway; EU: European Union, EMA: European Medicines Agency; FDA: US Food and Drug Administration; CFDA: China Food and Drug Administration; FDO: Food and Drug Organization (Iran’s National Regulatory Authority); HER2+: human epidermal growth factor receptor 2 positive; MHLW: Japan’s Ministry of Health, Labour and Welfare; MFDS: Ministry of Food and Drug Safety; MSD: Merck Sharp & Dohme; 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 [20]. The company also received EMA approval in December 2017 forapproval ofits trastuzumab biosimilar Herzuma (CT‑P6) in Europe [24]. It submitted a marketing application to FDA in July 2017 [6]. Although, this was rejected in April 2018 [26], the company resubmitted its application for approval of CT‑P6 in May 2018 [27].

Samsung Bioepis, a joint venture between South Korean electronics giant Samsung and biotechnology company Biogen, received marketing approval from the EMA in September 2017 [35].

Actavis/Amgen, Biocon/Mylan and Pfizer have submitted marketing applications to EMA for approval of their trastuzumab biosimilars in Europe [5,13,31]. 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 [15]. The pair re-submitted their application to EMA in December 2017 [18]. Pfizer received approval for their trastuzumab biosimilar Trazimera in June 2018 [33].

Biocon/Mylan received approval for their trastuzumab biosimilar, Ogivri (trastuzumab-dkst), from FDA in December 2017 [19].

Actavis/Amgen and Pfizer have also submitted marketing applications to FDA for approval of their trastuzumab biosimilars in the US [6, 31]. FDA, however, rejected Pfizer’s application in April 2018, requesting ‘additional technical information’ [32].

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, ‘biogenerics’ approved in Iran 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
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Source: EMA, US FDA

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