First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis

Abstract

Aims: To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17F, in subjects with mild plaque psoriasis.

Methods: Randomized, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous bimekizumab (8-640 mg) or placebo (NCT02529956).

Results: Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. No subject discontinued due to treatment-emergent adverse events and no severe adverse events were reported. Bimekizumab demonstrated fast onset of clinically-meaningful effects on skin of patients with mild psoriasis as early as Week 2. Maximal improvements (100% or near 100% reductions from baseline) in all measures of disease activity were observed between Weeks 8-12 in subjects receiving 160-640 mg bimekizumab. The duration of effect at doses ≥160 mg was evident up to Weeks 12-20 after a single intravenous dose, dependent on endpoint.

Conclusions: This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL-17A and IL-17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically-meaningful efficacy by Week 2, with a maximal or near-maximal magnitude of response that was maintained up to study Weeks 12-20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL-17A and IL-17F, including psoriasis.

Keywords: UCB4940; anti-IL17A; anti-IL17F; bimekizumab; interleukin-17; psoriasis.

© 2016 UCB BIOPHARMA SPRL. The British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Figures

Figure 1

Subject disposition. iv, intravenous. * Subject 00019 (bimekizumab 8 mg group) and subject 00111 (bimekizumab 480 mg group) withdrew themselves from the study. For both subjects, the reason for discontinuation was listed as withdrawal by subject and was not the result of an adverse event

Figure 2

Mean neutrophil count by treatment group (full analysis set); LNL, lower normal limit; UNL, upper normal limit. Note: 95% confidence intervals are included for the placebo and bimekizumab highest treatment groups only. The figure was based on protocol‐specified time after administration time points for the x‐axis; however, the time points presented in this figure are offset for each treatment group to avoid overlap of symbols and confidence intervals

Figure 3

Geometric mean (with 95% confidence intervals) plasma concentration‐time profile of bimekizumab by dose (pharmacokinetic per‐protocol set). LOQ, limit of quantitation; Note: the figure was based on protocol‐specified time after administration time points for the x‐axis; however, the time points presented in this figure are offset for each treatment group to avoid overlap of symbols and confidence intervals

Figure 4

Dose proportionality (pharmacokinetic per‐protocol set): individual area under the curve (AUC) vs. bimekizumab dose. Note: at bimekizumab 480 mg, the AUC was reported for five subjects. The AUC was not calculated for one subject because insufficient data points were available in the elimination phase of the pharmacokinetic profile

Figure 5

Mean percentage change from baseline in (A) LSS, (B) PASI and (C) PGA in the placebo and bimekizumab treatment groups (full analysis set). LSS, lesion severity score; PASI, Psoriasis Area and Severity Index; PGA, physician's global assessment. Note: 95% confidence intervals are included for the placebo and bimekizumab highest treatment groups only, to enable clarity of the plots. Note: figure was based on protocol‐specified time after administration time points for the x‐axis; however, the time points presented in this figure are offset for each treatment group to avoid overlap of symbols and confidence intervals