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 product is a proposed biosimilar to Amgen’s Neulasta (pegfilgrastim), which had worldwide sales of US$4.7 billion in 2016, making it a lucrative target for biosimilars manufacturers. The patents on Neulasta expired in the US in October 2015 and in Europe in August 2017 [1].

The marketing application for B12019 included ‘biosimilarity data from analytical, biofunctional and clinical studies comparing B12019 and Neulasta’. The company carried out two clinical studies, after taking advice from EMA. Results from these studies, according to Cinfa, ‘confirmed the analytical and biofunctional similarity of B12019 and Neulasta in highly sensitive clinical study settings’.

The pivotal study examined pharmacokinetic (PK) and pharmacodynamic (PD) comparability of 6 mg B12019 compared to 6 mg Neulasta. The single-dose, randomized, double-blind, two-way crossover study enrolled 172 healthy volunteers. The primary endpoints were the area under the plasma concentration-time curve (AUC) and the maximum concentration (C_max) for PK and the area under the effect curve (AUEC) for absolute neutrophil count (ANC) for PD.

The supportive study examined immunogenicity and PD comparability of 3 mg B12019 and 3 mg Neulasta in a multiple-dose, randomized, double-blind, three-period, two-sequence crossover study in 96 healthy volunteers. Primary endpoints were AUEC for PD and anti-drug antibody rate (ADA) for immunogenicity [2].

All clinical endpoints were met in both studies. PK comparability was demonstrated in the pivotal study, and PD comparability was demonstrated in both studies. No imbalance of ADA-positive samples was observed and neither anti-G-CSF nor neutralizing antibodies were detected for B12019 or Neulasta in both studies.

The submission marks the first biosimilar application for Cinfa Biotech, which was created in 2013 as part of the Spanish Cinfa Group. But Cinfa is not alone in its ambitions to produce a pegfilgrastim biosimilar. Rival biosimilars makers Biocon/Mylan, Coherus, Stada Arzneimittel/Gedeon Richter and Sandoz have also submitted marketing applications for their pegfilgrastim biosimilars to US Food and Drug Administration and EMA [3].

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EMA accepts application for pegfilgrastim biosimilar

References
1. Derbyshire M. Patent expiry dates for biologicals: 2016 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2017;6(1):27-30. doi:10.5639/gabij.2017.0601.006
2. GaBI Online - Generics and Biosimilars Initiative. Positive phase I results for Cinfa’s pegfilgrastim biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Oct 13]. Available from: www.gabionline.net/Biosimilars/News/Positive-phase-I-results-for-Cinfa-s-pegfilgrastim-biosimilar
3. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of pegfilgrastim [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Oct 13]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-of-pegfilgrastim

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