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Immunogenicity of biologicals: the role of post-translational modifications

Although produced under strict quality control(s) nascent endogenous proteins and glycoproteins (P/GP) are structurally heterogeneous and subject to further structural changes throughout their in vivo life cycle. A nascent polypeptide chain may be subject to co-translational modifications (CTMs) as it is extruded from the ribosome tunnel, e.g. the addition of oligosaccharide; edited for correct folding and initial oligosaccharide processing within the endoplasmic reticulum and subject to post-translational modifications (PTMs) during passage through the Golgi apparatus. The functional activity of a P/GP may be dependent on further chemical modifications (CMs), e.g. deamidation, enzymatic cleavage. These heterogeneities are compounded when determining the structure of a purified P/GP because further CMs may be introduced during its isolation, purification and characterization [1].

Extrapolation of indications in biosimilars: infliximab

Physicians may not be well informed about the scientific concept underlying the principle of extrapolating* indications for biosimilars. This in turn may lead them to distrust biosimilars, leading to a lower than expected uptake in Europe, especially in extrapolated indications. Members of the European Medicines Agency’s (EMA) Working Party on Similar Biological (Biosimilar) Medicinal Products (BMWP) address these concerns using extrapolation of indications in biosimilar infliximab as an example [1].

Non-clinical study shows similarity of biosimilar etanercept

The results of a non-clinical study of a candidate biosimilar etanercept (GP2015) has shown the similarity, with respect to in vitro and in vivo characteristics, of the biosimilar (GP2015) and its reference product, Amgen’s blockbuster autoimmune disease treatment Enbrel (etanercept).

Assessing structural comparability using NMR

Several biologicals will lose patent protection within the next few years, opening up the market for biosimilars [1]. According to US Food and Drug Administration (FDA) guidelines, biosimilar applicants should demonstrate biosimilarity using a stepwise approach, which includes structural and functional characterization, animal toxicity, pharmacokinetics and pharmacodynamics, immunogenicity, and clinical safety and effectiveness [2]. FDA expects extensive characterization of the proposed biosimilar and the reference product using state-of-the-art analytical technology including analysis of the protein (primary, secondary, tertiary, quaternary structure as well as post-translational modifications).

Biosimilars and treatment of IBD in Italy

In February 2015, the patent for infliximab expired in Italy.  Now, biosimilar CT-P13 products (Remsima and Inflectra), the first monoclonal antibody biosimilar of infliximab, are on the Italian market. In their recent paper, Annese et al. [1], assessed gastroenterologist’s view of the use of CT-P13 for the treatment of inflammatory bowel disease (IBD) in Italy. 

What makes physicians consider patients suitable for biosimilar infliximab

Prescribing physicians play an important role in the adoption of biosimilars in rheumatic diseases. Assessing physician perception of patients they consider as suitable for biosimilars may provide insights into eventual biosimilar adoption in clinical practice settings as well as any physician educational needs.

What internists should know about biologicals and biosimilars

Authors from the IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy discuss some of the most frequent concerns raised by internists about biosimilars [1].

Positive phase III results for adalimumab and trastuzumab biosimilars

Phase III studies of an adalimumab biosimilar from Momenta Pharmaceuticals (Momenta) and a trastuzumab biosimilar from Pfizer have, according to the companies, shown that the biosimilars are ‘equivalent’ compared to their respective originator biologicals.

Assessing analytical comparability for G-CSF biosimilars

According to the US Food and Drug Administration (FDA), a biosimilar is a biological product shown to be ‘highly similar to an FDA-approved biological product’, and which ‘has no clinically meaningful differences in terms of safety and effectiveness’. Only minor differences in clinically inactive components are allowable in biosimilars. Biosimilars of approved biologicals at the end of their patent life are expected to cost less but be as safe and effective for licensed clinical uses. To date, FDA has approved four biosimilars [1], while the European Union has approved more than 20 biosimilars [2].

Effectiveness of ESAs in treating anaemia in kidney disease and cancer patients

Erythropoiesis-stimulating agents (ESAs) are biological analogues of human erythropoietin used for the treatment of anaemia associated with chronic kidney disease (CKD) and chemotherapy treatment in cancer patients [1]. ESA biosimilars have been available on the Italian market since 2007. However, only limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs in routine care.