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Biosimilars of pegfilgrastim Posted 31/10/2014

Last update: 25 January 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 [2]

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 [3]. Biosimilar approved by EMA in July 2018 [4]. Submitted for approval in the US in December 2014 [5]. Approved in Canada in May 2018 [6].

Biocon/Mylan, India*/USA

Fulphila (MYL-1401H)

Submitted to EMA for approval in July 2016 [7]. Withdrawn from EMA August 2017 [8]. Submitted to FDA in February 2017. FDA issued CRL delaying approval in October 2017 [9]. Re-submitted to EMA for approval in December 2017 [10]. Approved by FDA in June 2018 [11]. Approved by EMA in September 2018 [12]. Launched in US in November 2018 [13].

Cadila Healthcare, India*

-

Plans to file for approval in US by end 2019 [14].

Cinfa Biotech/Mundipharma [15], 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)

Positive results from phase I trials announced in October 2015 [19] and July 2016 [20]. Submitted to FDA in October 2016 [21] and to EMA in November 2016 [22]. Rejected by FDA 12 June 2017 [23]. Approved by EC in September 2018 [24] and by FDA in November 2018 [25]. Launched in US in November 2018 [26].

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 [27]. Positive phase I results reported in October 2018 [28]

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)

Filed for approval in the US in November 2015 [16] and in the EU in February 2016 [17]. Rejected by FDA July 2016 [18] and withdrawn from EMA January 2017 [19]. Re-submitted to EMA for approval in October 2017 [20]

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 [34]. Application withdrawn from EMA in December 2016. Re-submitted to EMA in March 2018 [35].

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 [36]. Sandoz filed for approval of its pegfilgrastim biosimilar (LA-EP2006) in the US in November 2015 [29] and in the EU in February 2016 [30]. However, after a rejection by the FDA [31] 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 re-submitting its application to EMA in October 2017 [33] 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 [5] and received approval for Lapelga in Canada in May 2018 [6] and for Pelgraz from the EMA in July 2018 [4]. Biocon/ Mylan submitted an application for approval of its pegfilgrastim biosimilar to EMA in July 2016 [7]. Stada Arzneimittel/Gedeon Richter, submitted an application for approval of its pegfilgrastim biosimilar to the EMA in December 2015 [34] and re-submitted it in March 2018 [35]. Coherus submitted applications for approval of its pegfilgrastim biosimilar to FDA in October 2016 [21] and to EMA in November 2016 [22]. Coherus also received a rejection from FDA in June 2017 [23], but received EC approval in September 2018 [24] and FDA approval in November 2018 [25]. UK-based Mundipharma International and Spain-based Cinfa Biotech received EC approval for Pelmeg in November 2018 [18].

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 [8]. They also received a complete response letter (CRL) from the FDA delaying approval in October 2017 [9], but received approval in June 2018 [11]. The companies re-submitted their application to the EMA in September 2017 [10] and received approval for Fulphila in September 2018 [12].

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
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Source: Amgen, EMA, CDSCO

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