Biosimilars of bevacizumab Posted 02/06/2014

Last update: 8 November 2019

Bevacizumab is a humanized monoclonal antibody. It inhibits angiogenesis (the formation of new blood vessels) by blocking the action of vascular endothelial growth factor A (VEGF-A). Bevacizumab can therefore slow the growth of new blood vessels in tumours and is used to treat various cancers, including colorectal, lung, breast, glioblastoma, kidney and ovarian.

The originator product, Roche’s Avastin (bevacizumab), was approved by the US Food and Drug Administration (FDA) in February 2004 and by the European Medicines Agency (EMA) in January 2005 [1]. Avastin had 2016 sales of CHF 6.8 billion (Euros 5.95 billion) before the advent of biosimilars, see Table 1.

The patents on Avastin will expire in the US in July 2019 and in Europe in January 2022 [1]. There are estimated to be around 15 biosimilars of bevacizumab in development [2], of which just a few are presented below, see Table 1.

Table 1: Biosimilars and non-originator biologicals* of bevacizumab in development

Company name, Country

Product name

Stage of development

Amgen/Allergan, USA

Mvasi (ABP 215)

Approved by FDA in September 2017 [3] and by EC in January 2018 [4].

Apotex (Apobiologix), Canada

-

Biosimilar in pipeline – under clinical development

AstraZeneca/Fujifilm Kyowa Kirin Biologics, USA/Japan

FKB238

50:50 joint venture established August 2015. Phase I trial started in November 2014 [5]

Aurobindo Pharma, India*

-

Acquired four biosimilars from TL Biopharmaceutical AG in February 2017 [6]

Biocad, Russia*

BCD-021

Phase III trial in lung cancer completed in November 2014. Phase III trial in wet AMD withdrawn [7]. Non-originator biological approved in Russia in December 2015 [8]

BIOCND, South Korea

BCD500

Phase III trial ongoing

Biocon, India*

Krabeva

‘Similar biologic’ launched in India in November 2017 [9]. Phase I PK study in Europe completed. Phase III trial in NSCLC ongoing [10]

Bio‑Thera Solutions, China*

BAT1706

'Copy biological' currently being evaluated in a global phase III clinical trial [10]

BioXpress Therapeutics, Switzerland

-

In pipeline

Boehringer Ingelheim, Germany

BI 695502

Positive results from phase I trial reported in November 2016 [11]. Announced that it will only pursue biosimilars in the US in November 2018 [12]

Celltrion, South Korea

CT-P16

In pipeline

Coherus, USA

CHS-5217

Preclinical

Dr Reddy’s Laboratories, India*

DRZ_BZ

Phase III

Laboratorio Elea, Argentina*

Lumiere

Medicamento biológico similar approved in Argentina in August 2018 [13]

Hetero (Lupin), India*

Cizumab

‘Similar biologic’ launched in India in July 2016 [9]

Innovent Biologics, China*

IBI-305

Phase III study in AS completed March 2018. Submitted to CNDA in January 2019 [14]

Mabworks, China*

MIL60

Phase III

mAbxience, Spain (Argentina*)

Bevax (BEVZ92)

Medicamento biológico similar approved in Argentina [15]. Phase I trial in metastatic colorectal cancer completed in June 2017

Oncobiologics/Viropro, USA

ONS-1045

Biosimilar collaboration agreement signed in February 2013 for 6 biosimilars [16]. ONS-1045, met its primary and secondary endpoints in a phase I clinical trial in October 2015. Phase III trial expected to start in 2018.

Pfizer, USA

Zirabev (PF-06439535)

Approved by EC in February 2019 [4]. Approved by Japan's MHLW in June 2019 [17]

PlantForm, Canada

-

Preclinical

Prestige Biopharma, Singapore

HD204

Phase III trial in NSCLC expected to be completed in February 2021 [18]

Qilu Pharmaceutical, China*

-

Phase III

Reliance Life Sciences/Lupin, India*

Bevacirel

‘Similar biologic’ launched in India in July 2016 [9].

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

SB8

Phase III trial in lung cancer ongoing (April 2016) [19]. Collaborating with 3SBio for copy biologicals in China [20]

Shanghai Henlius Biotech (Fosun Pharma), China*

HLX04

Phase I trial in NSCLC started in May 2016

Tanvex BioPharma, Taiwan

TX16

Results of phase I PK trial in colorectal cancer in the US reported December 2017 [21]

TOT Biopharm, China*

-

Phase III

AMD: Age-related macular degeneration; AS: ankylosing spondylitis; CNDA: China National Drug Administration (formerly CFDA); EMA: European Medicines Agency; EC: European Commission; FDA: US Food and Drug Administration; NSCLC: non-small-cell lung cancer; PK: pharmacokinetics.
*See editors comment

Amgen is ready with its biosimilar well in advance of the patent expiry on Avastin, putting the biotech giant in a good position to be first on the market. In fact, the company has already received marketing approval for its bevacizumab biosimilar, Mvasi (ABP 215), from both the FDA [3] and the EC [4]. Pfizer also received approval from the EC in February 2019 for its bevacizumab biosimilar, Zirabev (PF 06439535) [4].

Editor's comment
It should be noted that ‘non-originator biologicals’ approved in Russia, ‘medicamento biológico similares’ approved in Argentina, ‘copy biologicals’ approved in China  and ‘similar biologics’ approved in India 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.          

Related Articles
Biosimilars of ranibizumab

Biosimilars of rituximab

Biosimilars of infliximab

Biosimilars of adalimumab

Biosimilars of trastuzumab

Biosimilars of cetuximab

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. Biosimilars on the horizon [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jun 2]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-on-the-horizon
3. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
5. GaBI Online - Generics and Biosimilars Initiative. AstraZeneca and Fujifilm Kyowa Kirin Biologics to collaborate on bevacizumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Oct 2]. Available from: www.gabionline.net/Pharma-News/AstraZeneca-and-Fujifilm-Kyowa-Kirin-Biologics-to-collaborate-on-bevacizumab-biosimilar
6. GaBI Online - Generics and Biosimilars Initiative. Aurobindo and Samsung BioLogics investing in biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Apr 14]. Available from: www.gabionline.net/Pharma-News/Samsung-BioLogics-and-Aurobindo-investing-in-biosimilars
7. GaBI Online - Generics and Biosimilars Initiative. Comparison of non-originator filgrastim with Neupogen finds no difference in neutropenia recovery periods [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Jun 12]. Available from: www.gabionline.net/Biosimilars/Research/Comparison-of-non-originator-filgrastim-with-Neupogen-finds-no-difference-in-neutropenia-recovery-periods
8. GaBI Online - Generics and Biosimilars Initiative. Bevacizumab non-originator biological approved in Russia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Mar 8]. Available from: www.gabionline.net/Biosimilars/News/Bevacizumab-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 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India
10. 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 8]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-copy-biologicals-accepted-for-review-in-China
11. GaBI Online - Generics and Biosimilars Initiative. Positive results for etanercept and bevacizumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Dec 9]. Available from: www.gabionline.net/Biosimilars/Research/Positive-phase-III-results-for-etanercept-and-adalimumab-biosimilars
12. GaBI Online - Generics and Biosimilars Initiative. Boehringer Ingelheim and Sandoz abandon biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Feb 28]. Available from: www.gabionline.net/Biosimilars/General/Boehringer-Ingelheim-and-Sandoz-abandon-biosimilars
13. GaBI Online - Generics and Biosimilars Initiative. Trastuzumab and bevacizumab products approved in Australia and Argentina [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/News/Trastuzumab-and-Bevacizumab-products-approved-in-Australia-and-Argentina
14. GaBI Online - Generics and Biosimilars Initiative. Monoclonal antibody copy biologicals accepted for review in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/News/Monoclonal-antibody-copy-biologicals-accepted-for-review-in-China
15 GaBI Online - Generics and Biosimilars Initiative. Similar biotherapeutic products approved and marketed in Latin America [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Jul 13]. Available from: www.gabionline.net/Biosimilars/General/Similar-biotherapeutic-products-approved-and-marketed-in-Latin-America
16. GaBI Online - Generics and Biosimilars Initiative. Oncobiologics and Viropro make biosimilar deal [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Jun 2]. Available from: www.gabionline.net/Biosimilars/News/Oncobiologics-and-Viropro-make-biosimilar-deal
17. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Japan [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Japan
18. GaBI Online - Generics and Biosimilars Initiative. Phase III trials started for bevacizumab and natalizumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. 
19. GaBI Online - Generics and Biosimilars Initiative. Samsung Bioepis starts phase III trial for bevacizumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Aug 5]. Available from: www.gabionline.net/Biosimilars/News/Samsung-Bioepis-starts-phase-III-trial-for-bevacizumab-biosimilar
20. GaBI Online - Generics and Biosimilars Initiative. Samsung Bioepis makes deals for copy biologicals in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Pharma-News/Samsung-Bioepis-makes-deals-for-copy-biologicals-in-China
21. GaBI Online - Generics and Biosimilars Initiative. Tanvex BioPharma submits filgrastim biosimilar to FDA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 8]. Available from: www.gabionline.net/Biosimilars/News/Tanvex-BioPharma-submits-filgrastim-biosimilar-to-FDA

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 © 2015 Pro Pharma Communications International. All Rights Reserved.

Source: ClinicalTrials.gov, EMA, EU Clinical Trials Register

Comments (3)

Response to ‘New bevacizumab biosimilar approved in Argentina’ posted 18/09/2018 - by Louis B, GaBI Online Editorial Office

Thank you for your valuable comments and insight received on 5 August 2018, we have followed-up on your suggestion and researched the issue further. We have added this news on the website and will make the necessary addition in the next update of the article ‘Biosimilars of bevacizumab’. We very much appreciate your kind feedback. Thank you for your interest in GaBI, and please continue with your valuable comments to GaBI Online. Best Regards, Louis

New bevacizumab biosimilar approved in Argentina posted 12/09/2018 - by Lucas

First posted 5/8/2018 ---- Lumiere - a bevacizumab biosimilar - approved for intravitreal use for age macular degeneration in Argentina.

Pfizer has biosimilar(PF-06439535) of bevacizumab on phase III posted 17/06/2015 - by zhaoshuyong

Pfizer has biosimilar(PF-06439535) of bevacizumab on phase III