Canada-based Apobiologix published analytical results demonstrating the similarity of their pegfilgrastim product to the US reference product, Amgen’s Neulasta (pegfilgrastim) [1].
Pegfilgrastim is a long-acting pegylated form of filgrastim, which requires only once-per-cycle administration for the management of cancer chemotherapy-induced neutropenia. The product requires fewer injections compared to non-pegylated filgrastim, which must be injected daily, thus increasing the likelihood of patient compliance. The originator product Neulasta is currently the only pegfilgrastim product available on the US market. There are several companies with applications under review by the US Food and Drug Administration (FDA) [2, 3], competing for the chance to be the first pegfilgrastim biosimilar approved in the US, thus potentially improving availability for this important drug.
The US Biologics Price Competition and Innovation Act of 2009 (BPCIA) established an abbreviated licensure pathway for biosimilars, known as the 351(k) pathway. FDA encourages a step-wise approach for the demonstration of biosimilarity of a biological with the US-licensed reference product, with analytical similarity forming the foundation of this approach [4, 5].
As the foundation of their pegfilgrastim biosimilarity programme, the Apobiologix team of Brokx et al. [1] examined the structure, biophysical characteristics, purity and biological activity of their pegfilgrastim in comparison to US-licensed pegfilgrastim. The amino acid sequences of the two products were determined to be identical by peptide mapping methods. The higher order structures of the molecules were confirmed to be highly similar based on a number of orthogonal biophysical techniques, and the PEG portions of the molecules were shown to be similar in size and polydispersity using Mass Spectrometry. Purity was evaluated by gel- and chromatography-based methods and the types of product-related impurities were found to be comparable between the two products, with similar or lower amounts of impurities found in the Apobiologix product. The biological activities of the two molecules were shown to be highly similar using an in vitro cell-based relative potency assay, anin vivomouse study and two receptor-binding assays.
The first step towards establishing biosimilarity of this pegfilgrastim molecule to Neulasta, namely demonstration of analytical similarity, appears to have been met. FDA evaluates proposed biosimilars using a totality-of-evidence approach, which includes evaluation of appropriate non-clinical and clinical data, including safety and efficacy. The authors mentioned that phase I and phase III clinical trials have also been completed.
Apobiologix’s Biologics License Application (BLA) for pegfilgrastim is under active review by FDA, and their pegfilgrastim product was co-developed with India-based Intas Pharmaceuticals. Apobiologix has been dedicated to the development of biosimilars since 2007, and has marketed the non-pegylated filgrastim molecule, a biosimilar of Amgen’s Neupogen (filgrastim), in the European Union and Canada since 2013 and 2015, respectively, with a BLA also under active review by FDA [6].
Conflict of interest
The authors of the research paper [1] did not provide the conflict of interest statement.
Abstracted by Stephen Brokx, PhD, Scientific Leader, Product Development, Apobiologix, a division of ApoPharma USA, Toronto, Canada
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References
1. Brokx S, Scrocchi L, Shah N, Dowd J. A demonstration of analytical similarity comparing a proposed biosimilar pegfilgrastim and reference pegfilgrastim. Biologicals. In press 2017.
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of pegfilgrastim [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Aug 18]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-of-pegfilgrastim
3. GaBI Online - Generics and Biosimilars Initiative. Mylan and Biocon submit pegfilgrastim biosimilar to EMA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Aug 18]. Available from: www.gabionline.net/Biosimilars/News/Mylan-and-Biocon-submit-pegfilgrastim-biosimilar-to-EMA
4. U.S. Food and Drug Administration. Guidance for industry. Scientific considerations for demonstrating biosimilarity to a reference product. April 2015 [homepage on the Internet]. [cited 2017 Aug 18]. Available from: www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291128.pdf
5. U.S. Food and Drug Administration. Guidance for industry: quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. April 2015 [homepage on the Internet]. [cited 2017 Aug 18]. Available from: www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm291134.pdf
6. Apobiologix. Apobiologix: focused on the development and distribution of biosimilar therapies [homepage on the Internet]. [cited 2017 Aug 18]. Available from: www.apobiologix.com/about/default.asp
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