A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Hanes, Vladimir; Chow, Vincent; Pan, Zhiying; Márkus, Richard

doi:10.1007/s00280-018-3695-4

Cited by 17 publications

(20 citation statements)

References 4 publications

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“…The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80–125%. These results were consistent with other similar studies in Caucasian, Japanese, Korean, and Chinese healthy volunteers ( Table 5 ) (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019).…”

Section: Discussionsupporting

confidence: 93%

“…TEAEs considered related to the study drug in this study were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin ® group. AE seemed to vary widely between these studies (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019), but there was no significant correlation with the dose. The %AE with 1 mg/kg ranged across studies from 33.3% to 55.0% for biosimilars and 32.3% to 48.8% for Avastin ® (EU-sourced).…”

Section: Discussionmentioning

confidence: 87%

“…The %AE with 3 mg/kg ranged across studies from 8.3% to 56.4% for biosimilars and 4.2% to 63.2% for Avastin ® (EU-sourced). The %AE with 5 mg/kg ranged across studies from 19.6% to 48.5% for biosimilars and 42.6% to 62.9% for Avastin ® (EU-sourced) ( Table 5 ) (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

Wang

Лонг

et al. 2019

Front. Pharmacol.

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Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the biosimilar TAB008 monoclonal antibody to bevacizumab (Avastin ® ) in normal healthy Chinese male volunteers. Methods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy Chinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose of TAB008 or Avastin ® over a 90-min infusion. The subjects were followed for 99 days after drug administration. Primary endpoints were bioequivalence of major pharmacokinetic parameters (AUC 0-t and AUC 0-∞ ) and maximum observed serum concentration (C max ). Secondary endpoints included safety and immunogenicity parameters. Results: The two groups of test subjects (49 subjects in the TAB008 group and 50 subjects in the Avastin ® group) were well matched in regards to all demographic and baseline characteristics. The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 103.66–118.33% for C max , 94.32–111.72% for AUC 0-t , and 94.69–112.23% for AUC 0-∞ ). Treatment-emergent adverse events (TEAEs) were reported for 24 (49.0%) subjects in the TAB008 group and 22 (44.0%) subjects in the Avastin ® group. TEAEs related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin ® group. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 TEAEs were reported for 1 (2.0%) subject in the TAB008 group and 3 (6.0%) subjects in the Avastin ® group. There were no Grade 4 or 5 TEAEs or serious adverse events (SAEs) during the study. Anti-drug antibody generation was reported once only in each group, and neutralizing antibody (Nab) analysis was negative upon follow-up. Conclusion: TAB008 attained pharmacokinetic similarity to bevacizumab, and was safe and well tolerated.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

Wang

Лонг

et al. 2019

Front. Pharmacol.

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“…Moreover, results confirm that bevacizumab-EU and bevacizumab-US are bioequivalent to each other, consistent with results from other phase I studies of bevacizumab biosimilars [16,17]. The PK results of this study are consistent with those of other phase I PK studies of (proposed) bevacizumab biosimilars which also demonstrated equivalence to the reference product [16][17][18][19][20][21][22][23][24][25][26]. However, direct comparisons of absolute PK parameters values between studies are generally not appropriate due to differences between the doses used (1 mg/kg, 3 mg/kg or 5 mg/kg), sample collection, and assessment methods [16][17][18][19][20][21][22][23][24][25][26].…”

Section: Discussionsupporting

confidence: 89%

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Shin

Lee

Choi

et al. 2020

Cancer Chemother Pharmacol

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Purpose To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US). Methods In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated. Results The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected. Conclusion This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. Clinicaltrials.gov identifier NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

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“…Although mCRC is one of the indications for which bevacizumab is most commonly prescribed in clinical practice, 54,55 it is a less sensitive patient population for comparing bevacizumab biosimilars with bevacizumab RP. In pivotal phase III trials in AUC inf and C max were similar across the 3 arms GMRs between treatment arms for C max and AUC inf , respectively, were 0.98 and 0.99 for ABP 215 vs. bevacizumab (US); 1.03 and 0.96 for ABP 215 vs. bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) vs. bevacizumab (EU) 90% CIs for the GMRs of AUC inf and C max were within the prespecified bioequivalence margin ABP 215 26 Randomized, open-label, single-dose study C max , AUC last , and AUC inf were similar across the three arms GMRs between treatment arms for C max , AUC last , and AUC inf , respectively, were 104%, 100%, and 99% for PF-06439535 vs. bevacizumab (EU); 110%, 104%, and 103% for PF-06439535 vs. bevacizumab (US); and 105%, 105%, and 105% for bevacizumab (EU) vs. bevacizumab (US) 90% CIs for the GMRs of C max , AUC last , and AUC inf were within the prespecified bioequivalence margin SB8 28 Randomized, open-label, single-dose study treatment-naive mCRC, adding bevacizumab RP to chemotherapy significantly improved PFS, but the impact on ORR was small and varied between studies. 56,57 Furthermore, ORR may not reliably predict PFS and OS in this patient population.…”

Section: Demonstrating Biosimilaritymentioning

confidence: 94%

Clinical and Regulatory Considerations for the Use of Bevacizumab Biosimilars in Metastatic Colorectal Cancer

Taı̈eb

Aranda

Raouf

et al. 2021

Clinical Colorectal Cancer

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Biosimilars e biological medicines highly similar to a licensed reference product (RP) e can mitigate the risk of drug shortages by providing treatment alternatives and, with their lower costs, increase patient access to medication and reduce health care expenditure. However, limited knowledge of biosimilar approval processes and lack of confidence in their quality and efficacy can limit their uptake. Importantly, biosimilars are approved based on tightly controlled regulatory pathways to demonstrate that the physical, chemical, and biological properties of the proposed biosimilar are highly similar to the RP, with no clinically meaningful differences. Initially, a battery of highly sensitive in vitro studies are performed, comparing critical quality attributes between the proposed biosimilar and RP. Subsequently, in vivo pharmacodynamic studies compare the activity and physiologic effects of the biosimilar and RP. Finally, clinical studies are conducted, including a pharmacokinetic equivalence study and a confirmatory comparative clinical trial. The latter is performed in the most sensitive patient population for which the RP is licensed, to provide the greatest possibility of identifying any clinically meaningful differences between the proposed biosimilar and RP. When equivalent safety and efficacy have been demonstrated in one setting, the totality of evidence, together with scientific justification that there are no anticipated differences between the RP and proposed biosimilar in mechanism of action, pharmacokinetics, immunogenicity or toxicity, allows extrapolation into indications where clinical studies were not performed with the proposed biosimilar. Here, we review the approval process for biosimilars, focusing on the licensing of bevacizumab biosimilars and their extrapolation to metastatic colorectal cancer.

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A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Cited by 17 publications

References 4 publications

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Clinical and Regulatory Considerations for the Use of Bevacizumab Biosimilars in Metastatic Colorectal Cancer

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