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Biosimilars of pegfilgrastim Posted 31/10/2014

Last update: 15 January 2021

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, before the advent of biosimilars.

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 (Australia/Canada)/ Neupeg (India)/ Neutropeg (Australia)/ Pelgraz (EU) (Apo-Peg)

‘Similar biologic’ approved in India in August 2007 [2]. Approved by EC in September 2018 [3]. Submitted for approval in the US in December 2014 [4]. Approved by Health Canada in May 2018 [5]. Approved by Australia's TGA in August 2019 [6].

Biocon/Mylan, India*/USA

Fulphila (MYL-1401H)

Approved by FDA in June 2018 [6]. Approved by EC in January 2019 [3]. Launched in US in November 2018. Launched in Australia and Canada in April 2020 [8, 9].

Biocure, South Korea

-

Preclinical

Cadila Healthcare, India*

-

Plans to file for approval in US by end 2019

Cinfa Biotech/Mundipharma, Spain/UK

Pelmeg (B12019)

Pelmeg approved by EC in November 2018 [ 3]. Pegfilgrastim Mundipharma approved by EMA in October 2019 [3]

Chong Kun Dang Pharmaceutical, South Korea

CKD-12101

Preclinical

Coherus Biosciences, USA

Udenyca (CHS-1701)

Approved by EC in September 2018 [3] and by FDA in November 2018 [7]. Launched in US in November 2018

Dr Reddy’s Laboratories, India*

Peg-grafeel

‘Similar biologic’ approved in India in May 2010 [2]

Fresenius Kabi, Germany 

MSB11455 

Acquired from Merck KGaA in September 2017. Positive phase I results reported in October 2018. Approval application submission accepted by EMA and FDA in May 2020 [10].

Gennova Biopharmaceuticals (Emcure), India*

Pegex

‘Similar biologic’ approved in India in January 2010 [2]

Jiangsu Hengrui Medicine, China*

Mecapegfilgrastim (HHPG-19K)

Phase III studies in breast cancer and NSCLC completed

Lupin, India*

Peg-filgrastim

‘Similar biologic’ approved in India in September 2013 [2]

Pfenex, USA

PF529

Candidate biosimilar under pre-clinical development

Pfizer, USA

Nyvepria (PF-06881894)

Approved by FDA in June 2020 [7] and approved by EC in November 2020 [3]

Sandoz, Switzerland

Ziextenzo (LA-EP2006)

Approved by EC in November 2018 [3]. Approved by FDA in November 2019 [7]. Approved by Australia's TGA in June 2019 [6], and by Health Canada in June 2020 [5].

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. Application withdrawn from EMA in December 2016. Resubmitted to EMA in March 2018 [11].

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; NSCLC: Non-small cell lung cancer; TGA: Therapeutic Goods Agency.
*See editor’s comment

Developers of pegfilgrastim biosimilars have not had an easy route, with a whole host of rejected applications littering the way. However, the path finally seems to have cleared with approvals now coming thick and fast.

Canada-based Apotex filed for approval of its pegfilgrastim biosimilar in the US in December 2014. The company received approval for Lapelga in Canada in May 2018 [5] and for Pelgraz from the EC in July 2018 [3].

Biocon/Mylan initially had to withdraw their application from the EMA and received a rejection from the FDA. However, they finally received approval for Fulphila from the FDA in June 2018 [7] and from the EC in September 2018 [3] and was launched in Australia and Canada in April 2020 [8, 9].

Spain-based Cinfa Biotech and UK-based Mundipharma International received EC approval for Pelmeg in November 2018 and for Pegfilgrastim Mundipharma in October 2019 [3].

Coherus’ pegfilgrastim biosimilar Udenyca (CHS-1701) received EC approval in September 2018 [3] and FDA approval in November 2018 [7].

The submission for approval of Fresenius Kabi’s pegfilgrastim biosimilars was accepted by EMA and FDA on 22 and 27 May 2020, respectively [10].

Pfizer’s biosimilar pegfilgrastim Nyvepria was approved by FDA in June 2020 [7] and by EC in November 2020 [3].

Generics maker Sandoz received EC approval for Ziextenzo in November 2018 [3] and FDA approval in November 2019 [7]. It has also been approved by Australia's TGA in June 2019 [6], and by Health Canada in June 2020 [5].

Stada Arzneimittel/Gedeon Richter, submitted an application for approval of its pegfilgrastim biosimilar to EMA in December 2015, but withdrew it in December 2016 and resubmitted it in March 2018 [11].

Other newcomers are South Korea’s Biocure with pegfilgrastim biosimilar in preclinical; and China’s Jiangsu Hengrui Medicine with Mecapegfilgrastim (HHPG-19K) copy biological pegfilgrastim completed Phase III studies in breast cancer and NSCLC.

Editor’s comment
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 but they are not universally accepted by regulatory bodies outside of the European Union (EU). It should be noted that ‘copy biologicals’ approved in China and ‘similar biologics’ approved in India might not have been authorized if they had been subjected to the strict regulatory processes required for approval of biosimilars in the EU.

Related article
Biosimilars of filgrastim

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. ‘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. Biosimilars approved in Europe. EMA approves adalimumab and pegfilgrastim biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Nov 25]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
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. Biosimilars approved in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Canada 
6. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Australia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 15]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Australia 
7. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Jan 25]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US
8. GaBI Online - Generics and Biosimilars Initiative. Biocon/Mylan launch pegfilgrastim biosimilar Fulphila in Australia [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 15]. Available from: www.gabionline.net/Biosimilars/News/Biocon-Mylan-launch-pegfilgrastim-biosimilar-Fulphila-in-Australia  
9. GaBI Online - Generics and Biosimilars Initiative. Pegfilgrastim biosimilar Fulphila launched in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 15]. Available from: www.gabionline.net/Biosimilars/News/Pegfilgrastim-biosimilar-Fulphila-launched-in-Canada 
10. GaBI Online - Generics and Biosimilars Initiative. Fresenius Kabi’s pegfilgrastim biosimilar accepted for review by EMA and FDA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jan 15]. Available from: www.gabionline.net/Biosimilars/News/Fresenius-Kabi-s-pegfilgrastim-biosimilar-accepted-for-review-by-EMA-and-FDA 
11. 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

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Source: Amgen, EMA, CDSCO

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