New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept

Abstract

Etanercept is a recombinant fusion protein approved for the treatment of TNF-α mediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in their in vitro activity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA.

Comment on “New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept”

“…In their publication, Miranda-Hernandez et al 2016 [ 1 ] present data on the physicochemical and biological comparability of Infinitam® with the reference etanercept innovator product, Enbrel®. As part of a physicochemical similarity exercise (not comparability), the authors present data on glycan microheterogeneity using hydrophilic interaction ultra-performance-liquid-chromatography (HILIC-UPLC) on three batches of Enbrel and one batch of Infinitam (Figure 3 panel b of Miranda-Hernandez et al).…”

Variability of intended copies for etanercept (Enbrel®): Data on multiple batches of seven products

“…Published data are available from only one comparative clinical trial between Enbrel Ò and one of the seven ICs described in this analysis. 15 Conducted in 59 patients with moderate to severe RA, this study used a double-blind, randomized, threearm design to evaluate the PD effect of Infinitam compared with innovator etanercept. 15 All patients received concomitant methotrexate (MTX) treatment.…”

“…15 Conducted in 59 patients with moderate to severe RA, this study used a double-blind, randomized, threearm design to evaluate the PD effect of Infinitam compared with innovator etanercept. 15 All patients received concomitant methotrexate (MTX) treatment. In two of the treatment arms, patients received Infinitam for 24 weeks, whereas in the third arm, patients were switched from innovator etanercept after 12 weeks to receive Infinitam.…”

“…Although the authors claim comparable biological effects between treatments based on the change in a number of markers of inflammatory response (e.g., B-cell activating factor protein, erythrocyte sedimentation rate, C-reactive protein, TNF, rheumatoid factor) and disease parameters (Disease Activity Score in 28 joints [DAS28]), the study was not designed or powered to show bioequivalence. 15 In this same publication, the authors presented data on the physicochemical and biological comparability of Infinitam and innovator etanercept. However, the N-glycan profile of one batch of innovator etanercept presented was markedly different from the other batches, and contained glycan species that were not resolved in the other batches.…”

“…8 Several publications 11 have claimed a degree of structural and biochemical comparability between ICs and innovator etanercept. [12][13][14][15][16] However, a critique of one of these publications has suggested that the analyses conducted were insufficient to make a comprehensive evaluation of biochemical similarity, 17 while another publication demonstrated differences in the primary amino acid sequence in one IC compared with innovator etanercept. 16 In this article, the results for the analytical assessments of multiple lots of six ICs and a single lot of one IC are reported against the licensed etanercept innovator product (Enbrel Ò ).…”