A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab

Hummel, Matthew; Bosje, Tjerk; Shaw, Andrew; Liu, Mark Shiyao; Barve, Abhijit; Kothekar, Mudgal; Socinski, Mark A.; Waller, Christiane

doi:10.1007/s00432-021-03628-0

Cited by 9 publications

(15 citation statements)

References 27 publications

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“…In healthy male subjects, the majority (≥ 89%) of patients in the MYL-1402O, EU-and US-sourced reference bevacizumab treatment arms tested positive for ADAs on day 15. A similar decrease in ADA-positive subjects over time was observed across the trial arms [3]. Furthermore, in an analysis of the total trial population, higher levels of ADAs did not appear to have clinically significant effects on the pharmacokinetics of bevacizumab in healthy male subjects (Table 2) [3].…”

Section: Immunogenicitymentioning

confidence: 55%

“…A parallel study design was selected as the half-life of bevacizumab is approximately 20 days. Although a subtherapeutic dose (1 mg/kg) of bevacizumab was administered to limit exposure in healthy subjects, this dose was within the range where the pharmacokinetics of bevacizumab are expected to be linear [3]. MYL-1402O demonstrated pharmacodynamic equivalence and similarity in physicochemical properties to EUsourced bevacizumab in pre-clinical studies (Table 2).…”

Section: Clinical Pharmacologymentioning

confidence: 99%

“…In patients with stage IV non-squamous NSCLC, the incidence of treatment-emergent ADAs was 6.5% in 337 MYL-1402O recipients and 4.8% in 334 reference bevacizumab recipients [5] In healthy male subjects, the incidence of ADA-positive subjects in the MYL-1402O arm was comparable to the EU-and US-sourced bevacizumab arms at all measured time points (days 15-99) [3] Subjects with higher levels of ADAs compared with lower levels of ADAs did not demonstrate clinically relevant differences in bevacizumab AUC ∞ , AUC t and C max [3]…”

Section: [3] Immunogenicitymentioning

confidence: 99%

“…Lextemy is approved for the same indications as bevacizumab, apart from recurrent ovarian cancer [2]. The pharmacokinetic similarity of MYL-1402O to EU-and US-sourced reference bevacizumab has been demonstrated [3]. This article summarizes, from an EU perspective, the key features of MYL-1402O and its clinical use in the treatment of solid cancers, focusing on non-squamous non-small cell lung cancer (NSCLC).…”

Section: Introductionmentioning

confidence: 99%

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MYL-1402O: A Bevacizumab Biosimilar

Lee

2021

Targ Oncol

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MYL-1402O (Abevmy ® , Lextemy ® ) is a biosimilar of the reference anti-vascular endothelial growth factor antibody bevacizumab. Abevmy ® is approved for use in all indications for which reference bevacizumab is approved, including the treatment of non-small cell lung cancer (NSCLC) and other solid cancers. Lextemy ® is approved for all indications as reference bevacizumab, except in recurrent ovarian cancer. MYL-1402O has similar physicochemical and pharmacodynamic properties to those of reference bevacizumab, and the pharmacokinetic similarity of the agents has been shown in healthy male subjects. MYL-1402O demonstrated clinical efficacy equivalent to that of reference bevacizumab in patients with non-squamous NSCLC. The tolerability, safety and immunogenicity profiles of MYL-1402O were consistent with those of reference bevacizumab. The role of reference bevacizumab in the management of solid cancers is well established and MYL-1402O provides an effective biosimilar alternative for patients requiring bevacizumab therapy.

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Section: Immunogenicitymentioning

confidence: 55%

Section: Clinical Pharmacologymentioning

confidence: 99%

Section: [3] Immunogenicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MYL-1402O: A Bevacizumab Biosimilar

Lee

2021

Targ Oncol

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“…Subsequently, the bioequivalence with regard to pharmacokinetic (PK) parameters and comparability of most treatment-emergent adverse events (TEAEs) was confirmed in a single-center, randomized, double blind, three-arm, parallel-group phase I study (ClinicalTrials.gov Identifier: NCT02469987). 16,17 The primary objective of the current confirmatory study was to demonstrate the equivalence of MYL-1402O to reference bevacizumab with regard to efficacy, safety, and immunogenicity, when used as a first-line treatment for stage IV nsNSCLC in combination with carboplatin and paclitaxel (CP).…”

Section: Introductionmentioning

confidence: 99%

Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

Socinski

Waller

Idris³

et al. 2021

Ther Adv Med Oncol

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Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

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A randomized, double‐blind, single‐dose study to assess bioequivalence of MB02 biosimilar after manufacturing iteration and reference bevacizumab

Schwabe¹,

Cole

Espigares-Correa³

et al. 2023

Pharmacology Res & Perspec

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To investigate and compare the pharmacokinetic (PK) profiles of MB02 products, before and after optimizing the manufacturing process, and reference bevacizumab to establish bioequivalence between them. In this randomized, double‐blind, single dose, parallel study, 114 healthy male volunteers were randomized 1:1:1 to receive a 1 mg/kg intravenous dose of MB02‐SP, MB02‐DM, or US‐bevacizumab. The follow‐up period was 100 days. PK similarity between them was determined using the standard bioequivalence criteria (0.80–1.25) for the area under the serum concentration–time curve from time 0 extrapolated to infinity and the maximum observed serum concentration. Study results showed that the PK profiles of bevacizumab were similar. Statistical analysis demonstrated that for each pairwise comparison there were no differences. The 90% CIs for the ratios of geometric least squares means were fully contained within the predefined similarity acceptance limits and ranged from 0.899 to 1.12 for area under the curve and from 0.887 to 1.11 for maximum concentration. A total of 159 adverse events were reported by 76 subjects who received the study drug. The majority (90.6%) of the reported adverse events were grade 1 in severity, with 9.4% as grade 2 in severity. None were considered as grade 3, 4, or 5. Treatment‐induced anti‐drug antibodies incidence was 21.6%, 33.3%, and 23.7% for the treatment of MB02‐SP, MB02‐DM, and US‐bevacizumab, respectively. No subjects showed treatment‐induced neutralizing anti‐drug antibodies. This study demonstrates the PK, safety, and immunogenicity similarity and bioequivalence of MB02‐SP, MB02‐DM, and the reference product bevacizumab.

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A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab

Cited by 9 publications

References 27 publications

MYL-1402O: A Bevacizumab Biosimilar

MYL-1402O: A Bevacizumab Biosimilar

Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

A randomized, double‐blind, single‐dose study to assess bioequivalence of MB02 biosimilar after manufacturing iteration and reference bevacizumab

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