4-Week toxicity study of biosimilar natalizumab in comparison to Tysabri<sup>®</sup> by repeated intravenous infusion to cynomolgus monkeys

Grabowski, Tomasz; Leuschner, J; Gad, Shayne C.

doi:10.1080/01480545.2020.1722155

Drug and Chemical Toxicology

2020

DOI: 10.1080/01480545.2020.1722155

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4-Week toxicity study of biosimilar natalizumab in comparison to Tysabri^® by repeated intravenous infusion to cynomolgus monkeys

Tomasz Grabowski

J Leuschner²,

Shayne C. Gad

Abstract: Subject of this validation was the quantitative determination of Tysabri ® (Natalizumab) in serum samples. This assay employed the quantitative antibody sandwich enzyme immunoassay technique (ELISA). A microtiter plate was coated with a specific anti-Natalizumab antibody.After blocking, calibration samples, quality control samples (QCs) or study samples were pipetted into the wells. After washing, the HRP-conjugated secondary anti-Natalizumab antibody

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“…15,20,21 Previous pharmacokinetic/pharmacodynamic and safety studies in healthy participants provided evidence to support PB006 phase 3 studies involving patients with RRMS. 22,23 The primary objective of the Antelope study was to confirm equivalent efficacy between biosim-NTZ and ref-NTZ in patients with RRMS by assessing magnetic resonance imaging (MRI)-based end points supported by clinical, safety, and immunogenicity secondary end point analyses. The potential impact of switching from ref-NTZ to biosim-NTZ on efficacy outcomes and immunogenicity was also assessed in a subpopulation analysis.…”

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Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

et al. 2023

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ImportanceProposed biosimilar natalizumab (biosim-NTZ) PB006 is the first biosimilar monoclonal antibody therapy developed for multiple sclerosis (MS) treatment.ObjectiveTo evaluate matching efficacy, safety, and immunogenicity between biosim-NTZ and reference natalizumab (ref-NTZ) in patients with relapsing-remitting MS (RRMS).Design, Setting, and ParticipantsThe Antelope trial was a phase 3, parallel-group, randomized, active-controlled study, conducted between October 2019 and March 2021, with last patient follow-up visit on August 23, 2021. The study took place in 48 centers in 7 countries. Of 531 patients with RRMS aged 18 to 60 years screened, 266 were excluded before randomization in line with study criteria. Eligible participants had 1 or more documented relapse within the previous year and either 1 or more gadolinium-enhancing T1-weighted or 9 or more T2-weighted brain lesions, Kurtzke Expanded Disability Status Scale score of 0 to 5.0 (inclusive), and John Cunningham virus index of 1.5 or less at screening. One patient withdrew consent before dosing.InterventionsIntravenous infusions every 4 weeks of biosim-NTZ, 300 mg, or ref-NTZ, 300 mg (1:1 randomization), from week 0 to week 44 (end-of-study visit: week 48). At week 24, the ref-NTZ group was rerandomized and 30 patients were switched to biosim-NTZ for the remainder of the study.Main Outcomes and MeasuresThe primary end point was the cumulative number of new active lesions on magnetic resonance imaging (new gadolinium-enhancing T1-weighted lesions and new/enlarging T2-weighted lesions without double counting) over 24 weeks. Additional end points included further magnetic resonance imaging parameters, annualized relapse rate, and Kurtzke Expanded Disability Status Scale score. Safety, tolerability, and immunogenicity assessments included adverse events, laboratory evaluations, and positivity for anti–John Cunningham virus antibodies and antinatalizumab antibodies.ResultsA total of 264 participants (mean [SD] age, 36.7 [9.38] years; 162 [61.4%] female) received treatment with biosim-NTZ (n = 131) or ref-NTZ (n = 133). At week 24, the model-based mean difference in cumulative number of new active lesions between biosim-NTZ and ref-NTZ treatment groups was 0.17 (least square means [SE]: biosim-NTZ, 0.34 [0.34]; ref-NTZ, 0.45 [0.28]; 95% CI, –0.61 to 0.94 within the prespecified margins of ±2.1). No significant differences between treatment groups were observed across secondary efficacy end points, safety, tolerability, or immunogenicity assessments.Conclusions and RelevanceBiosim-NTZ matched ref-NTZ in efficacy, safety, and immunogenicity for patients with RRMS in the tested setting. This phase 3 trial supports proposed biosim-NTZ as a biosimilar alternative to ref-NTZ for treating RRMS.Trial RegistrationClinicalTrials.gov Identifier: NCT04115488

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Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

et al. 2023

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Biosimilars: An Update

Bhojaraj

Kumar

Ghosh

et al. 2021

Int J Nutr Pharmacol Neurol Dis

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4-Week toxicity study of biosimilar natalizumab in comparison to Tysabri^® by repeated intravenous infusion to cynomolgus monkeys

Cited by 2 publications

References 20 publications

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

Biosimilars: An Update

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4-Week toxicity study of biosimilar natalizumab in comparison to Tysabri® by repeated intravenous infusion to cynomolgus monkeys

Cited by 2 publications

References 20 publications

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

Biosimilars: An Update

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4-Week toxicity study of biosimilar natalizumab in comparison to Tysabri^® by repeated intravenous infusion to cynomolgus monkeys