A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Márkus, Richard

doi:10.1136/annrheumdis-2015-208914

Cited by 72 publications

(85 citation statements)

References 19 publications

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“…In this study, the percentages of subjects over time with binding ADA formation and nADA formation were similar among all study arms. The results were also consistent with other recent studies evaluating biosimilars of Humira . In the M923 study, the proportion of subjects with a confirmed ADA response, the rate of ADA seroconversion over time, and the occurrence of nADAs were in line with that reported by Kaur et al .…”

Section: Discussionsupporting

confidence: 92%

“…The results were also consistent with other recent studies evaluating biosimilars of Humira . In the M923 study, the proportion of subjects with a confirmed ADA response, the rate of ADA seroconversion over time, and the occurrence of nADAs were in line with that reported by Kaur et al . A lower ADA response (44%) has been reported with LBAL, a Humira biosimilar that is currently in development .…”

Section: Discussionsupporting

confidence: 91%

“…A lower ADA response (44%) has been reported with LBAL, a Humira biosimilar that is currently in development . The ADA responses with M923 and other Humira biosimilars are higher (>70%) than historically reported for Humira registration trials or in a real‐world study in RA . The lower ADA response may reflect the fact that in some of these studies, patients may have also been receiving agents that could suppress the immune system and thereby reduce the incidence of antibody formation .…”

Section: Discussionmentioning

confidence: 84%

“…The sample size (N = 324) was determined based on previously published estimates of variability in the primary PK parameters . More specifically, Kaur et al.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetic equivalence, comparable safety, and immunogenicity of an adalimumab biosimilar product (M923) to Humira in healthy subjects

Hillson

Mant

Rosano³

et al. 2018

Pharmacology Res & Perspec

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The aims of this randomized, double‐blind, three‐arm, single‐dose study were to demonstrate pharmacokinetic (PK) equivalence of the adalimumab biosimilar M923 (hereafter referred to as “M923”) to each of 2 reference products, and to assess M923's safety and immunogenicity. Primary PK endpoints were maximum observed concentration (C max), area under the curve (AUC) from time 0 extrapolated to infinity (AUC0‐inf), and AUC from time 0 to 336 hours (AUC0‐336). Secondary endpoints included safety and immunogenicity assessments. Healthy subjects were randomized 1:1:1 to receive a 40‐mg dose of M923 (n = 107); adalimumab US Humira (n = 105), hereafter referred to as “US Humira”; or adalimumab EU Humira (n = 103), hereafter referred to as “EU Humira.” PK equivalence was demonstrated for all primary PK endpoints. Geometric least squares means ratios (GMRs) for C max, AUC0‐inf, and AUC0‐336 were 99.4, 100.9, and 100.5, respectively, between the M923 and EU Humira arms and 102.6, 104.2, and 102.9 between the M923 and US Humira arms. The 90% confidence intervals of the GMRs for all PK endpoints were within prespecified confidence bounds of 80%‐125%. Adverse event rates were similar across the M923 (47.7%), US Humira (50.9%), and EU Humira (53.3%) arms and were generally mild (73.7%) or moderate (22.0%). The proportion of subjects with a confirmed antidrug antibody (ADA) response was similar across study arms. This study demonstrated bioequivalent PK among M923, US Humira, and EU Humira and demonstrated that the PK parameters were consistent with similar safety and tolerability profile and ADA response rates.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 84%

“…The sample size (N = 324) was determined based on previously published estimates of variability in the primary PK parameters . More specifically, Kaur et al.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetic equivalence, comparable safety, and immunogenicity of an adalimumab biosimilar product (M923) to Humira in healthy subjects

Hillson

Mant

Rosano³

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

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“…This is important to understand because if such sensitive assays are used during biosimilar development it may lead to the perception that the ADAs are much higher than originally seen with the reference products. However, in comparative biosimilar studies using more sensitive methods, serum levels in patients receiving reference product should be similar to those in patients receiving the proposed biosimilar . Increased sensitivity may also lead to potentially false positives; including patients who are naive to drug and have ADAs prior to exposure.…”

Section: Development Of Biosimilars: Analytical Preclinical and Clinmentioning

confidence: 99%

Biosimilars: what the dermatologist should know

Yamauchi¹,

Crowley

Kaur

et al. 2018

Acad Dermatol Venereol

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Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g. cell lines), processes or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic and clinical assessment for similarity. The goal of the phase 3 clinical development programme for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints and statistical methods. Based on the clinical trial results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practising clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases.

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Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double‐blind Study in Healthy Subjects

Chow

Mytych

Das

et al. 2023

Clinical Pharm in Drug Dev

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ABP 654 is a proposed biosimilar to ustekinumab reference product (RP) which works through antagonism of interleukin‐12 and interleukin‐23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including some forms of plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. A randomized, double‐blinded, single‐dose, 3‐arm, parallel‐group study was conducted to assess the pharmacokinetic (PK) similarity of ABP 654 with ustekinumab RP sourced from the United States (US) and the European Union (EU); the PK similarity of ustekinumab US versus ustekinumab EU; and the comparative safety, tolerability, and immunogenicity of all 3 products. A total of 238 healthy subjects were randomized 1:1:1 and stratified by gender and ethnicity (Japanese versus non‐Japanese) to receive a single 90 mg subcutaneous injection of ABP 654 or ustekinumab US or ustekinumab EU. PK similarity was established based on 90% confidence intervals (CIs) for the primary endpoints of area under the concentration‐time curve from time 0 extrapolated to infinity (AUCinf) and maximum observed serum concentration (Cmax) being contained within the prespecified margin of 0.8–1.25. No clinically meaningful differences in immunogenicity were found among the 3 products. Adverse events were similar between treatment groups and consistent with the safety profile of ustekinumab RP. Results indicate that ABP 654, ustekinumab US and ustekinumab EU share similar PK and safety profiles.

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A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

Cited by 72 publications

References 19 publications

Pharmacokinetic equivalence, comparable safety, and immunogenicity of an adalimumab biosimilar product (M923) to Humira in healthy subjects

Pharmacokinetic equivalence, comparable safety, and immunogenicity of an adalimumab biosimilar product (M923) to Humira in healthy subjects

Biosimilars: what the dermatologist should know

Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double‐blind Study in Healthy Subjects

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