Biosimilar Reference Study PK Outcomes (and Immunogenicity Study Design Reference Candidate Product Population PD where reported) Outcomes Adalimumab ABP501 US and EU Randomised, Healthy 90% CIs for the No subjects were [1] (Amgen) Humira single-blind, volunteers geometrical mean positive for 40mg single-dose, (n=203) test-to-reference Drug antibodies three-arm, ratios for area (ADA) at baseline. parallel-group under the serum Over the course of study (1:1:1) concentration time the study 36 (54%), curve (AUC) from 38 (55%) and 45 time 0 extrapolated (67%) participants in to infinity (AUCinf), the ABP501, Humira AUC from time 0 to (US) and Humira the last quantifiable (EU) arms concentration respectively (AUClast) and developed binding maximum ADAs. Neutralising concentration ADAs were detected (Cmax) were within in 12 (18%), 15 (22%) the pre-specified and 14 (21%) equivalence criteria subjects in the of 0.80 and 1.25. ABP501, Humira (US) and Humira (EU) arms respectively. FKB327 US and EU Randomized, Healthy 90% CIs for the Approximately 5% of [2] (Fujifilm Kyowa Humira volunteers ratios of area under subjects had Kirin Biologics) 40mg parallel-group (n=180) concentration–time detectable ADA at study (1:1:1) curve up to last baseline. At last nonzero value sampling, 69.5%, (AUC0–t), 73.3% and 70.0% of area FKB327, Humira (EU) under and Humira (US) concentration–time participants curve extrapolated respectively were to infinity positive for ADAs. and peak serum concentration (Cmax) geometric means were in the acceptance range for bioequivalence of 0.80–1.25 For the secondary PK parameter endpoints, was equivalent in all treatment comparisons; t½ 90%CI for the FKB327:US-Humira comparison extended below the pre-specified lower limit of 0.8 (0.78) whilst the two other comparisons were within the limit.
Biosimilar Candidate Reference Product Study Design Study Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Adalimumab ABP501 (Amgen) US and EU Humira 40mg Randomised, single-blind, single-dose, three-arm, parallel-group study (1:1:1) Healthy volunteers (n=203) 90% CIs for the geometrical mean test-to-reference ratios for area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time 0 to the last quantifiable concentration (AUClast) and maximum concentration (Cmax) were within the pre-specified equivalence criteria of 0.80 and 1.25. No subjects were positive for antibodies (ADA) at baseline. Over the course of the study 36 (54%), 38 (55%) and 45 (67%) participants in the ABP501, Humira (US) and Humira (EU) arms respectively developed binding ADAs. Neutralising ADAs were detected in 12 (18%), 15 (22%) and 14 (21%) subjects in the ABP501, Humira (US) and Humira (EU) arms respectively. [1] FKB327 (Fujifilm Kyowa Kirin Biologics) US and EU Humira 40mg Randomized, parallel-group study (1:1:1) Healthy volunteers (n=180) 90% CIs for the ratios of area under concentration–time curve up to last nonzero value (AUC0–t), area under concentration–time curve extrapolated to infinity and peak serum concentration (Cmax) geometric means were in the acceptance range for bioequivalence of 0.80–1.25 For the secondary PK parameter endpoints, was equivalent in all treatment comparisons; t½ 90%CI for the FKB327:US-Humira comparison extended below the pre-specified lower limit of 0.8 (0.78) whilst the two other comparisons were within the limit. Approximately 5% of subjects had detectable ADA at baseline. At last sampling, 69.5%, 73.3% and 70.0% of FKB327, Humira (EU) and Humira (US) participants respectively were positive for ADAs. [2] Drug
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