Pharmacokinetics and pharmacodynamics of a proposed tocilizumab biosimilar MSB11456 versus both the US-licensed and EU-approved products: a randomized, double-blind trial

Schwabe, Christian; Illes, Andras; Ullmann, Martin; Ghori, Vishal; Vincent, Emmanuelle; Petit-Frere, Corinne; Monnet, Joëlle; Racault, Anne Sophie; Wynne, Chris

doi:10.1080/1744666x.2022.2060204

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…A total of 4 (10.00%) and 3 (8.11%) subjects tested positive for treatment‐induced ADA throughout the study for the test and reference groups, respectively. The total rate of ADA positivity in the present study was lower than that reported in other tocilizumab biosimilar studies, 13 , 14 , 15 on account of the different immunogenicity assessment period (28 days vs. 48 or 57 days). Due to the limited number of ADA‐positive subjects, subgroup analysis of bioequivalence and safety for ADA‐positive subjects was not feasible, thus the effect of the immunogenic responses on PK and safety could not be assessed.…”

Section: Discussioncontrasting

confidence: 89%

“…Three clinical studies have been conducted to explore the bioequivalence of other tocilizumab biosimilars in recent years, in which the PK similarity of tocilizumab biosimilars have been exhibited. 13 , 14 , 15 The objective of this phase I study was to evaluate the PK similarity of the proposed biosimilar HS628 compared with the reference tocilizumab (Actemra®) in healthy Chinese male subjects. The study also aimed to demonstrate similar safety and immunogenicity profiles of HS628 to the reference tocilizumab in this population of subjects.…”

Section: Introductionmentioning

confidence: 99%

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A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects

Cheng

Gui

et al. 2023

Clinical Translational Sci

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This study aimed to evaluate the pharmacokinetic (PK) similarity of the proposed biosimilar HS628 compared with the reference tocilizumab (Actemra®) and also to demonstrate similar safety and immunogenicity profiles in healthy Chinese male subjects. Eighty eligible subjects were randomized into two treatment groups in a 1:1 ratio to receive a single intravenous infusion of HS628 or tocilizumab at 4 mg/kg over 60 min. Blood samples were collected at the scheduled time points for PK and immunogenicity analysis. PK biosimilarity was determined using the standard bioequivalence criteria 80%–125%. A total of 77 subjects received the study drug and completed the study. The main PK parameters were similar for the test and reference groups. The ratio of geometric least‐squares means (GMR) and its 90% CIs for AUC0–t, AUC0–∞, and Cmax between the test group and reference group were 1.06 (1.00–1.12), 1.07 (1.00–1.14), and 1.04 (0.99–1.10), respectively, which were fully within the predefined bioequivalent range of 80%–125%. The incidence of treatment‐emergent adverse events (TEAEs) was similar for HS628 and tocilizumab (p > 0.05). The most common TEAEs were decreased fibrinogen, decreased neutrophils, pharyngalgia, oral ulcer, decreased leukocytes, and increased erythrocyte sedimentation rate. The results of the present study provide strong evidence to support the PK similarity and bioequivalence of HS628 and tocilizumab. The safety and immunogenicity profiles of HS628 were also shown to be similar to those of the reference tocilizumab.

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Section: Discussioncontrasting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects

Cheng

Gui

et al. 2023

Clinical Translational Sci

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Section: Discussionmentioning

confidence: 99%

“…These results further support the similarity between MSB11456 and EU-approved tocilizumab and build on evidence supporting the PK, PD, safety and immunogenic similarity of MSB11456 to the US-licensed and EU-approved tocilizumab in healthy subjects. 12 To ensure population homogeneity, which is important to maximise sensitivity to detect potential differences between the proposed biosimilar product and the reference product, the participants in our study were all Caucasian, from Eastern Europe, with long-standing RA, a bodyweight <100 kg and, as noted above, were predominantly biological naïve. These population characteristics could also be considered a limitation of the study as they do not allow generalisability of our findings.…”

Section: Discussionunclassified

“…It has demonstrated PK, PD, safety and immunogenic similarity to the US-licensed and EU-approved tocilizumab in studies in healthy subjects. 12 13 The aim of this clinical study (NCT04512001) was to evaluate the efficacy, immunogenicity and safety of MSB11456 compared with the EU-approved tocilizumab in patients with moderate-to-severe active RA who had experienced an inadequate clinical response to at least one DMARD (either synthetic or biologic) and were receiving a stable dose of methotrexate. Additional aims were to evaluate the long-term efficacy of MSB11456 and the effects on efficacy, safety and immunogenicity of a single treatment transition from EU-approved tocilizumab to MSB11456.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study

Zubrzycka-Sienkiewicz,

Klama,

Ullmann

et al. 2024

RMD Open

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ObjectiveTo evaluate the efficacy, immunogenicity and safety of the proposed biosimilar MSB11456 versus European Union (EU)-approved tocilizumab reference product in patients with rheumatoid arthritis (RA) in a multicentre, randomised, double-blind, multinational, parallel-group study (NCT04512001).MethodsAdult patients with moderate-to-severe active RA and inadequate clinical response to ≥1 disease-modifying antirheumatic drug (synthetic or biologic) receiving methotrexate were randomised to receive 24 weekly subcutaneous 162 mg injections of either MSB11456 or EU-approved tocilizumab. Equivalence between treatments was considered if the 95% CI (European Medicines Agency)/90% CI (US Food and Drug Administration) for the difference in mean change from baseline to week 24 in Disease Activity Score-28 Joint Count with erythrocyte sedimentation rate (DAS28-ESR) between treatments was entirely within prespecified equivalence intervals (−0.6 to 0.6 and −0.6 to 0.5, respectively). At week 24, patients were rerandomised to continued treatment or MSB11456. Secondary efficacy endpoints to week 52, and safety and immunogenicity to week 55 were also evaluated.ResultsAt week 24, the least squares mean difference in the change from baseline in DAS28-ESR between treatments was 0.01 (95% CI −0.19 to 0.22) in the 604 randomised patients. Similarity between treatments was shown for all other efficacy, safety and immunogenicity endpoints, including in patients who switched from EU-approved tocilizumab to MSB114466.ConclusionsTherapeutic equivalence was demonstrated for efficacy endpoints, and safety and immunogenicity analyses support the similarity of the two treatments. The results of this study strengthen the evidence that the proposed biosimilar MSB11456 and EU-approved tocilizumab exert similar clinical effects.

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Pharmacokinetics and Safety of Intravenous Candidate Biosimilar CT‐P47 and Reference Tocilizumab: A Randomized, Double‐Blind, Phase 1 Study

Haranaka,

Eto,

Tanaka

et al. 2024

The Journal of Clinical Pharma

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CT‐P47 is a candidate biosimilar of tocilizumab. This 12‐week, randomized, double‐blind, parallel‐design, phase 1 study aimed to demonstrate pharmacokinetic (PK) equivalence of CT‐P47 and reference tocilizumab. Participants were healthy Japanese adults aged 18–55 years. Participants were randomized (1:1:1) to receive a single intravenous dose (8 mg/kg) of CT‐P47, EU‐approved tocilizumab (EU‐tocilizumab), or US‐licensed tocilizumab (US‐tocilizumab). Primary PK endpoints were area under the concentration–time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum serum concentration. Additional PK variables, safety, and immunogenicity were evaluated. The study was conducted from January 20 to May 26, 2023, in three centers in Japan. In total, 133 male participants were randomized (n = 45 to CT‐P47, n = 44 to EU‐tocilizumab, and n = 44 to US‐tocilizumab). For all primary PK variables, 90% confidence intervals of the ratio of geometric least squares means were within the predefined equivalence margin of 0.80‐1.25. Secondary PK variables were similar across groups. The most common treatment‐emergent adverse event (TEAE) was neutrophil count decreased, occurring in 15 (33.3%), 13 (30.2%), and 12 (27.3%) participants in the CT‐P47, EU‐tocilizumab, and US‐tocilizumab groups, respectively. There were no serious TEAEs, deaths, or study drug discontinuations due to TEAEs. Few participants were anti‐drug antibody (ADA)‐ or neutralizing antibody (NAb)‐positive. At the end of study, four (8.9%), one (2.3%), and two (4.5%) participants in the CT‐P47, EU‐tocilizumab, and US‐tocilizumab groups, respectively, were ADA‐positive; two (4.4%), zero (0%), and one (2.3%) in the respective groups were NAb‐positive. CT‐P47 demonstrated PK equivalence and comparable safety to EU‐ and US‐tocilizumab.

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Pharmacokinetics and pharmacodynamics of a proposed tocilizumab biosimilar MSB11456 versus both the US-licensed and EU-approved products: a randomized, double-blind trial

Cited by 9 publications

References 18 publications

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects

Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study

Pharmacokinetics and Safety of Intravenous Candidate Biosimilar CT‐P47 and Reference Tocilizumab: A Randomized, Double‐Blind, Phase 1 Study

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