Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis

Abstract

Risankizumab, a humanized monoclonal antibody that targets interleukin-23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis. A phase 1, single-dose study evaluated risankizumab pharmacokinetics and safety/tolerability in healthy white (18 and 300 mg subcutaneous [SC]), Japanese (18, 90, and 300 mg SC and 200, 600, and 1200 mg intravenous [IV]), and Chinese (18, 90, and 300 mg SC) subjects; pharmacokinetic data were analyzed using noncompartmental methods. Risankizumab pharmacokinetic data from phase 2/3 studies in Japanese patients with plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis following multiple SC doses of 75 mg or 150 mg were analyzed using a population pharmacokinetic approach along with data from the phase 1 and global phase 1 to 3 studies. Risankizumab plasma exposures (peak plasma concentration and area under the concentration-time curve) were approximately dose-proportional across 18- to 300-mg SC or 200- to 1200-mg IV doses. Risankizumab terminal elimination half-life (harmonic mean 27-34 days) was comparable across doses and ethnicities. Risankizumab exposures were approximately 20% to 30% higher in Japanese and Chinese healthy subjects compared with white healthy subjects or in Japanese patients compared with non-Japanese patients. After accounting for body-weight differences, risankizumab exposures were comparable across ethnicities. Overall, there was no ethnic impact on risankizumab pharmacokinetics, and the small difference in exposure due to body weight has no clinical relevance.

Keywords: Japanese patients; erythrodermic psoriasis; ethnicity; generalized pustular psoriasis; plaque psoriasis; risankizumab.

Figure 1

Risankizumab mean plasma concentration‐time profile following single subcutaneous (SC) doses in panels A, B, and C or intravenous (IV) doses in panel D in healthy subjects.

Figure 2

Impact of covariates on risankizumab steady‐state exposures. ADA indicates antidrug antibody; AUC, area under the plasma concentration‐time curve in dosing interval at steady state; C_max, maximum plasma concentration at steady state; hs‐CRP, high‐sensitivity C‐reactive protein. Points and squares represent median values, and error bars represent 95%CIs of the normalized exposure ratios across 200 simulation replicates. The vertical black dashed line shows an exposure ratio of 1 relative to the reference group, and the shaded area represents the 0.8 to 1.25 default equivalence boundaries.

Figure 3

Visual predictive checks across phase 2/3 studies in Japanese patients with psoriasis who received risankizumab 75 mg SC (A) or 150 mg SC (B) at weeks 0 and 4 and every 12 weeks (q12w) thereafter using the updated population pharmacokinetic model. The black circles represent observed data; the lines represent observed median (solid black) and observed 5%/95% percentiles (dashed); the shaded regions represent the 95%CIs for the simulated median (green) and simulated 5%/95% percentiles (blue).