Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial

Psoriasis, a chronic immune-mediated inflammatory skin disease, affects approximately 2% of the global population. Eighty to ninety percent of patients have plaque psoriasis, and the extent of the affected surface areas of the body and the degree of redness, hardening, and scaling of the skin define its severity. In addition to its negative effect on well-being and quality of life, moderate-to-severe psoriasis has comorbidities including increased risk of heart disease and stroke. Approximately 25% of psoriasis patients have moderate-to-severe disease.

Genome-wide association studies have previously linked a variant in the genes for the IL-23 receptor and the p19 subunit of IL-23, or IL-23A, to psoriasis susceptibility. BI 655066 is a fully-human IgG₁ mAb selective for IL-23A. In this phase I proof-of-concept study, Krueger et al evaluated the results of administering a single-rising-dose of BI 655066 to patients with moderate-to-severe plaque psoriasis (J Allergy Clin Immunol 2015, in press). The primary objective was to assess the safety and tolerability of BI 65066, which was done via physical examinations, vital signs, electrocardiogram, clinical laboratory tests, and occurrence of adverse events.  However, mechanistic effects of IL-23 blockade were explored by histologic methods, deep RNA sequencing, and quantitative RT-PCR methods.

The study, the first of its kind, found that the majority of patients well-tolerated single-dose BI 655066. The patients who received the antibody showed clinical improvement after 2 weeks that was maintained for up to 66 weeks after treatment. After 12 weeks, 87% of treated patients experienced a decrease in  the Psoriasis Area and Severity Index of  at least 75% (PASI75). The treatment and placebo groups reported a similar frequency of adverse events. Strong inhibition of IL-17 and disease-related genes related to the IL-23/Th17 axis was measured in antibody-treated patients.  Treatment responses were maintained in most patients until 24 weeks and a smaller subset of patients followed without additional treatment maintained clearing of psoriasis for 10 months or more.  The results support a new model for treating psoriasis and raise the possibility of attaining long-term remission from a single drug intervention.