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.

Clinical Pharmacokinetics and Pharmacodynamics of Risankizumab in Psoriasis Patients

“…1; Table 3). There was no apparent difference in risankizumab pharmacokinetics between healthy subjects and patients with psoriasis [13,16]. Risankizumab exposures were 22-31% higher in healthy Chinese and Japanese subjects compared with healthy Caucasian subjects; this small difference in exposure was a result of the fixed-dosing regimen and the lower body weight for Chinese and Japanese subjects compared with Caucasian subjects [13].…”

“…An approximately dose proportional increase in risankizumab exposure was observed following repeated administration of 90 and 180 mg subcutaneous doses in the global phase II study [17,23], and between 75 and 150 mg subcutaneous doses in the Japanese phase II/III studies [13].…”

“…An overview of all studies conducted to date that are pertinent to risankizumab clinical pharmacology is presented in Table 1 (three phase I studies in healthy subjects and psoriasis patients) and Table 2 (seven phase II and III studies in patients with plaque psoriasis or GPP/EP); these studies evaluated the pharmacokinetics, immunogenicity, safety, and tolerability, and, in phase II and III studies, the efficacy of risankizumab. Population pharmacokinetic and exposure-response analyses for efficacy and safety, as well as analyses for the impact of immunogenicity on pharmacokinetics, safety, and efficacy, were performed using combined data from these phase I, II, and III studies to support the overall characterization of risankizumab clinical pharmacology, as well as the clinical dosing recommendation [12][13][14][15]. High-level results and conclusions from these studies and analyses are summarized in the following sections.…”

“…Single-dose pharmacokinetics of risankizumab were evaluated in two studies, Study 1 in Caucasian, Japanese, and Chinese healthy volunteers, and Study 2 in patients with psoriasis following either intravenous or subcutaneous administrations across doses ranging from 0.01 to 5 mg/kg intravenously, 200 to 1200 mg intravenously, 0.25 to 1 mg/ kg subcutaneously, and 18 to 300 mg subcutaneously [13,16]. Intensive plasma samples for pharmacokinetic assessment were collected in these studies.…”

“…Risankizumab geometric mean C trough values in Japanese patients with psoriasis, at weeks 16 and 52, were 2.06 µg/ mL and 1.64 µg/mL, respectively, based on pooled data of Japanese patients across all four global phase III and Japanese phase II/III studies [13], approximating the exposures in non-Japanese subjects. In addition, risankizumab exposures in Japanese patients with moderate-to-severe plaque psoriasis (with or without psoriatic arthritis) were comparable with those with GPP or EP [13]. Table 3 Geometric mean (mean, %CV) of risankizumab plasma pharmacokinetic parameters following single IV doses ranging from 0.01 to 5 mg/kg, and single SC doses of 0.25 or 1 mg/kg in subjects with moderate-to-severe psoriasis (Study 2)…”