Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab/Humira, in healthy subjects.

To compare the pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a biosimilar of adalimumab, with European Union (EU)-approved Humira and US-licensed Humira after single subcutaneous doses in healthy subjects. In a randomized, double-blind, parallel-group study, 180 healthy subjects received by subcutaneous injection 40 mg of EU-Humira, or US-Humira, or FKB327, in a 1:1:1 ratio, stratified by bodyweight. Pharmacokinetics, local tolerability, immunogenicity, adverse events, vital signs, electrocardiography and laboratory safety tests were assessed prior to and up to 1536 h after treatment. The pharmacokinetics of FKB327 were similar to those of both EU- and US-Humira. The 90% confidence interval for the ratios of AUC0-t , AUC0-inf , and Cmax geometric means were in the acceptance range for bioequivalence of 0.80-1.25 for all three pairwise comparisons by analysis of covariance with baseline characteristics age, body weight and (for Cmax only) sex as covariates. Tolerability of all three treatments was equally acceptable, and there were no differences in safety profile or immunogenicity among the three treatments. Overall, antidrug antibodies were detected in approximately 70% of subjects who received each treatment; higher titres were associated with faster elimination of adalimumab. The study demonstrated pharmacokinetic similarity of FKB327 with EU- and US-Humira. FKB327 was well tolerated by healthy subjects, with adverse effects similar to Humira. If clinical similarity to Humira, including efficacy, can be shown in patients, FKB327 will meet the criteria for biosimilarity to Humira.

Puri A ，Niewiarowski A ，Arai Y ，Nomura H ，Baird M ，Dalrymple I ，Warrington S ，Boyce M ... -  《-》

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

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 (Cmax ), 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 Cmax , 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.

Hillson J ，Mant T ，Rosano M ，Huntenburg C ，Alai-Safar M ，Darne S ，Palmer D ，Pavlova BG ，Doralt J ，Reeve R ，Goel N ，Weilert D ，Rhyne PW ，Chance K ，Caminis J ，Roach J ，Ganguly T ... -  《Pharmacology Research & Perspectives》

Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects.

Wynne C ，Altendorfer M ，Sonderegger I ，Gheyle L ，Ellis-Pegler R ，Buschke S ，Lang B ，Assudani D ，Athalye S ，Czeloth N ... -  《-》

A randomized, double-blind, single-dose, two-arm, parallel study comparing pharmacokinetics, immunogenicity and tolerability of branded adalimumab and its biosimilar LBAL in healthy male volunteers.

Park KR ，Chung H ，Yang SM ，Lee S ，Yoon SH ，Cho JY ，Jang IJ ，Yu KS ... -  《-》

GP2017, an adalimumab biosimilar: pharmacokinetic similarity to its reference medicine and pharmacokinetics comparison of different administration methods.

von Richter O ，Lemke L ，Haliduola H ，Fuhr R ，Koernicke T ，Schuck E ，Velinova M ，Skerjanec A ，Poetzl J ，Jauch-Lembach J ... -  《-》