Biosimilars of pegfilgrastim Posted 31/10/2014

Last update: 12 April 2019

Pegfilgrastim is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (G-CSF) analogue filgrastim. It serves to stimulate the level of white blood cells (neutrophils). Pegfilgrastim treatment can be used to stimulate bone marrow to produce more neutrophils (white blood cells) to fight infection in patients undergoing chemotherapy.

The originator product, Amgen’s Neulasta (pegfilgrastim), was approved by the US Food and Drug Administration (FDA) in January 2002 and by the European Medicines Agency (EMA) in August 2002 [1]. Neulasta had worldwide sales of US$4.7 billion in 2016.

The patents on Neulasta expired in the US in October 2015 and expired in Europe in August 2017 [1]. Some of the pegfilgrastim biosimilars and non-originator biologicals* approved or in development are presented in Table 1.

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

Company name, Country

Product name

Stage of development

Adello Biologics, USA

TPI‑120

Phase I

Apotex (Apobiologix)/ Intas Biopharmaceuticals/ Accord Healthcare, Canada/India*/USA

Lapelga (Canada)/ Neupeg (India)/ Pelgraz (EU) (Apo-Peg)

‘Similar biologic’ approved in India in August 2007 [2]. Biosimilar approved by EMA in July 2018 [3]. Submitted for approval in the US in December 2014 [4]. Approved in Canada in May 2018  

Biocon/Mylan, India*/USA

Fulphila (MYL-1401H)

Approved by FDA in June 2018 [6]. Approved by EC in January 2019 [7]. Launched in US in November 2018

Cadila Healthcare, India*

-

Plans to file for approval in US by end 2019

Cinfa Biotech/Mundipharma [8], Spain/UK

Pelmeg (B12019)

Completed two phase I trials in healthy subjects [16]. Submitted to EMA for approval in October 2017 [17]. Approved by EC in November 2018 [18].

Chong Kun Dang Pharmaceutical, South Korea

CKD-12101

Preclinical

Coherus Biosciences, USA

Udenyca (CHS-1701)

Approved by EC in September 2018 [10] and by FDA in November 2018 [11]. Launched in US in November 2018

Dr Reddy’s Laboratories, India*

Peg-grafeel

‘Similar biologic’ approved in India in May 2010 [3]

Fresenius Kabi, Germany 

MSB11455 

Acquired from Merck KGaA in September 2017. Positive phase I results reported in October 2018.

Gennova Biopharmaceuticals (Emcure), India*

Pegex

‘Similar biologic’ approved in India in January 2010 [3]

Lupin, India*

Peg-filgrastim

‘Similar biologic’ approved in India in September 2013 [15]

Pfenex, USA

PF529

Candidate biosimilar under pre-clinical development

Pfizer, USA

HSP-130

Phase I

Sandoz, Switzerland

Ziextenzo (LA-EP2006)

Approved by EC in November 2018 [9]. Resubmitted to FDA in April 2019

Siam Bioscience, Thailand

SBS 6002

Positive results for CMC analytical and non-clinical biosimilarity studies reported in July 2017

Stada Arzneimittel/Gedeon Richter, Germany/Hungary

-

Submitted to EMA for approval in December 2015 [12]. Application withdrawn from EMA in December 2016. Resubmitted to EMA in March 2018 [13].

USV, India*

-

Approval received from DCGI to initiate phase III clinical studies in India. Phase III clinical studies in Europe initiated in September 2015. Pre-IND meeting with FDA held. Phase I in US planned. 

CMC: Chemistry and Manufacturing Controls; CRL: Complete Response Letter; DCGI: Drug Controller General of India; EU: European Union; EMA: European Medicines Agency; FDA: US Food and Drug Administration.
*See editor’s comment

Generics maker Sandoz was one of the frontrunners in the race to biosimilar pegfilgrastim. The company has already completed two phase III trials comparing biosimilar pegfilgrastim to Amgen’s Neulasta in breast cancer patients. Sandoz filed for approval of its pegfilgrastim biosimilar (LA-EP2006) in the US in November 2015 and in the EU in February 2016. However, after a rejection by the FDA and withdrawing its application to the EMA [32], things were no longer looking so rosy and its competitors were fast catching up. Sandoz is now back in the running after resubmitting its application to EMA in October 2017 and to the FDA in April 2019 and receiving EC approval for Ziextenzo in November 2018 [18].

Canada-based Apotex filed for approval of its pegfilgrastim biosimilar in the US in December 2014 and received approval for Lapelga in Canada in May 2018 [5] and for Pelgraz from the EMA in July 2018 [3]. Biocon/Mylan submitted an application for approval of its pegfilgrastim biosimilar to EMA in July 2016. Stada Arzneimittel/Gedeon Richter, submitted an application for approval of its pegfilgrastim biosimilar to the EMA in December 2015 and resubmitted it in March 2018 [13]. Coherus submitted applications for approval of its pegfilgrastim biosimilar to FDA in October 2016 and to EMA in November 2016. Coherus also received a rejection from FDA in June 2017 but received EC approval in September 2018 [10] and FDA approval in November 2018 [11]. UK-based Mundipharma International and Spain-based Cinfa Biotech received EC approval for Pelmeg in November 2018 [9].

Biocon/Mylan were also experiencing setbacks after they were required to withdraw their application from 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 could be issued for the site. They also received a complete response letter (CRL) from the FDA delaying approval in October 2017 but received approval in June 2018 [6]. The companies resubmitted their application to the EMA in September 2017 and received approval for Fulphila in September 2018 [7].

Editor’s comment
It should be noted that ‘similar biologics’ approved in India 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 article
Biosimilars of filgrastim

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. ‘Similar biologics’ approved and marketed in India [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/General/Similar-biologics-approved-and-marketed-in-India
3. GaBI Online - Generics and Biosimilars Initiative. EMA approves adalimumab and pegfilgrastim biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/EMA-approves-adalimumab-and-pegfilgrastim-biosimilars
4. GaBI Online - Generics and Biosimilars Initiative. Apotex pegfilgrastim biosimilar under FDA review [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Feb 20]. Available from: www.gabionline.net/Biosimilars/News/Apotex-pegfilgrastim-biosimilar-under-FDA-review 
5. GaBI Online - Generics and Biosimilars Initiative. Pegfilgrastim biosimilar Lapelga approved in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/Pegfilgrastim-biosimilar-Lapelga-approved-in-Canada 
6. GaBI Online - Generics and Biosimilars Initiative. FDA approval for pegfilgrastim biosimilar Fulphila [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/FDA-approval-for-pegfilgrastim-biosimilar-Fulphila
7. GaBI Online - Generics and Biosimilars Initiative. EC approval for pegfilgrastim biosimilar Fulphila [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Feb 5]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-pegfilgrastim-biosimilar-Fulphila 
8. GaBI Online - Generics and Biosimilars Initiative. Mundipharma buys Spanish biosimilars’ maker Cinfa Biotech [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Pharma-News/Mundipharma-buys-Spanish-biosimilars-maker-Cinfa-Biotech
9. GaBI Online - Generics and Biosimilars Initiative. EC approval for pegfilgrastim biosimilars Pelmeg and Ziextenzo [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-pegfilgrastim-biosimilars-Pelmeg-and-Ziextenzo
10. GaBI Online - Generics and Biosimilars Initiative. EC approval for adalimumab and pegfilgrastim biosimilars Hulio and Udenyca [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-adalimumab-and-pegfilgrastim-biosimilars-Hulio-and-Udenyca
11.  GaBI Online - Generics and Biosimilars Initiative. FDA approves adalimumab and pegfilgrastim biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-adalimumab-and-pegfilgrastim-biosimilars
12. 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 2016 Nov 18]. Available from: www.gabionline.net/Pharma-News/Richter-and-DM-Bio-make-deal-for-trastuzumab-biosimilar
13. GaBI Online - Generics and Biosimilars Initiative. Stada resubmits biosimilar pegfilgrastim but stops adalimumab development [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Pharma-News/Stada-resubmits-biosimilar-pegfilgrastim-but-stops-adalimumab-development

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 Pharma Communications International. All Rights Reserved.

Source: Amgen, EMA, CDSCO

Comments (0)