Physicochemical and functional characterization of a biosimilar adalimumab ZRC-3197

Bandyopadhyay, Sanjay; Mahajan, Mukesh; Mehta, Tulsi; Singh, Arun Kumar; Parikh, Alomi O.; Gupta, Ajit K; Kalita, Pankaj; Patel, Mihir; Mendiratta, Sanjeev Kumar

doi:10.2147/bs.s75573

Cited by 24 publications

(23 citation statements)

References 19 publications

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“…Cadila Healthcare Limited of the Zydus Group has developed an adalimumab biosimilar (Exemptia; ZRC‐3197). Extensive physicochemical and biological comparability data showed the test adalimumab (Exemptia) to be highly similar to the reference adalimumab …”

Section: Discussionmentioning

confidence: 97%

A prospective, randomized, double‐blind, multicentre, parallel‐group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC‐3197) and adalimumab (Humira) in patients with rheumatoid arthritis

Jani

Gupta²,

Bhatia³

et al. 2015

Int J of Rheum Dis

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AimIn this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA).MethodIn this multicentre, prospective, randomized, double‐blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints – C‐reactive protein (DAS28‐CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed.ResultsAfter 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28‐CRP score was −2.1 ± 1.09 and −2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study.ConclusionThe results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

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Section: Discussionmentioning

confidence: 97%

A prospective, randomized, double‐blind, multicentre, parallel‐group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC‐3197) and adalimumab (Humira) in patients with rheumatoid arthritis

Jani

Gupta²,

Bhatia³

et al. 2015

Int J of Rheum Dis

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“…28 The primary and secondary structures of ZRC3197 and reference adalimumab are identical, and no differences were detected in aggregation or in the profile of lowmolecularweight fragments between these two biopharma ceuticals. 29 Charge heterogeneity, glycan profiles and other posttranslational modifications were also highly similar between ZRC3197 and reference adalimumab. Functional properties, including affinity for TNF and FcγRIIIa receptors and in vitro TNFneutralizing activity, were also highly similar.…”

Section: Bow015mentioning

confidence: 76%

“…A comparative toxicology study conducted in animals showed no significant differences between ZRC3197 and reference adalimumab in vivo. 29 The Cadila Healthcare Laboratory (India) conducted a clinical trial in India that compared ZRC3197 and ref erence adalimumab in 120 patients with RA. The results of this trial have not been published in a peerreviewed journal nor have they been presented at a major meeting in abstract form.…”

Section: Bow015mentioning

confidence: 99%

Biosimilars in rheumatology: current perspectives and lessons learnt

2015

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Biosimilars, based on biopharmaceuticals approved by regulatory agencies that are no longer under patent protection, have efficacy and safety comparable to their reference products, and are a new therapeutic option to treat inflammatory diseases. Biosimilars must be distinguished from 'biomimics' or 'biocopies', which are marketed in some countries but have not been evaluated according to the stringent regulatory pathway used for biosimilars. CT-P13, based on infliximab, was the first biosimilar approved for the treatment of inflammatory diseases; however, some countries did not allow extrapolation of indications to all eight diseases for which the reference drug infliximab is approved. Antidrug antibodies can reduce drug levels and affect clinical efficacy, but although available data suggest that biosimilars and their reference products have comparable immunogenicity, this important property might differ between individual biopharmaceuticals. This Review discusses biosimilars already approved within the past 3 years to treat rheumatic diseases, as well as others that are currently under development. The main challenges posed by biosimilars are also addressed, such as the extrapolation of indications to diseases only studied for the reference drug, and the definition of strategies for adequate pharmacovigilance to monitor biosimilars after marketing approval.

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“…Exemptia™ ( Cadila Healthcare ) Bandyopadhyay and coworkers [40] reported on the physicochemical properties and in vivo pharmacokinetic and toxicology profile of Exemptia™ in the journal Biosimilars and concluded that the molecule displayed highly similar characteristics to adalimumab. It should be noted that studies from non-indexed publications were not included in this review, and therefore the data from this publication were not extracted.…”

Section: Resultsmentioning

confidence: 99%

Biosimilars for the Treatment of Chronic Inflammatory Diseases: A Systematic Review of Published Evidence

et al. 2016

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BackgroundClinicians are required to assimilate, critically evaluate, and extrapolate information to support appropriate use of biosimilars across indications.ObjectivesThe objective of this study was to systematically collate all published data in order to assess the weight (quantity and quality) of available evidence for each molecule and inform and support healthcare decision-making in chronic inflammatory diseases.MethodsMEDLINE®, EMBASE®, and ISI Web of Science® were searched to September 2015. Selected conference proceedings were searched from 2012 to July 2015. Studies disclosing biosimilars with unique identifiers were categorized by originator, study type, and indication. Risk of bias assessments were performed. Intended copies were differentiated as commercially available agents without evidence of rigorous comparative biosimilarity evaluations.ResultsProposed biosimilars for adalimumab, etanercept, infliximab, and rituximab are reported in the published literature. Across indications, approved biosimilars infliximab CT-P13, SB2, and etanercept SB4 have published studies involving the largest number of patients or healthy subjects (n = 1405, 743, and 734, respectively), mostly in rheumatoid arthritis. At data cut-off, only CT-P13 had published data in ankylosing spondylitis (n = 250; randomized control trial) and ulcerative colitis/Crohn’s disease (n = 336; observational studies). Published data were not available for ongoing studies in psoriasis patients. Four intended copies were identified in published studies (total: n = 1430; n = 1372 in observational studies). Thematic analysis of non-empirical publications showed that indication extrapolation remains an issue, particularly for gastroenterologists.ConclusionsWhile most agents display a moderate to high degree of similarity to their originator in the published studies identified, large discrepancies persist in the overall amount and type of data available in the public domain. Significant gaps exist particularly for intended copies, reinforcing the need to maintain a clear differentiation between these molecules and true biosimilars.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-016-0201-6) contains supplementary material, which is available to authorized users.

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Physicochemical and functional characterization of a biosimilar adalimumab ZRC-3197

Cited by 24 publications

References 19 publications

A prospective, randomized, double‐blind, multicentre, parallel‐group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC‐3197) and adalimumab (Humira) in patients with rheumatoid arthritis

A prospective, randomized, double‐blind, multicentre, parallel‐group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC‐3197) and adalimumab (Humira) in patients with rheumatoid arthritis

Biosimilars in rheumatology: current perspectives and lessons learnt

Biosimilars for the Treatment of Chronic Inflammatory Diseases: A Systematic Review of Published Evidence

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