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 is a chronic immune-mediated inflammatory skin disease with a global incidence of approximately 2%. The extent of the affected body surface area and degree of erythema, induration, and scaling in four areas define its severity, and approximately 25% of patients have moderate-to-severe disease. Genome-wide association studies have linked variants in the gene for the IL-23 receptor and the p19 subunit of IL-23 to psoriasis susceptibility. IL-23 induces differentiation of T_H17 cells and T_H22 cells. The former are a primary cellular source of proinflammatory cytokines, including IL-17, and the latter are a primary source of IL-22. Both interleukins can mediate the development of the epidermal hyperplasia and tissue inflammation that occurs in psoriasis.

Krueger et al present the first-in-human proof-of-concept study to evaluate the clinical and biological effects of BI 655066 in patients with moderate-to-severe psoriasis. BI 655066 is a novel, fully human IgG₁ mAb selective for IL-23A. It binds to IL-23A with high affinity and blocks the biologic activity of IL-23 (J Allergy Clin Immunol 2015; 136(1):116-124).

Thirty-nine patients received single-dose BI 655066 intravenously, subcutaneously, or placebo. The patients who received the antibody showed clinical improvement after two weeks that, in a subset of those treated, 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 three groups reported adverse events with similar frequency.  The authors measured strong inhibition of IL-17 and disease-related genes related to the IL-23/Th17 axis, in addition to a significant correlation between treatment-associated molecular changes and improvement in PASI scores. The results support a new model for treating psoriasis and raise the possibility of attaining long-term remission from a single drug intervention.