A new monoclonal antibody, guselkumab, is being developed by Janssen as a potential treatment for the autoimmune condition psoriasis
The autoimmune condition psoriasis is a relapsing-remitting disease that typically results in itchy, red, scaly patches developing on the skin. There are several forms, and it is fairly common, affecting up to 4% of the population.
The precise causes remain unknown, but it is believed to be genetic in origin, and results from the autoimmune system attacking normal skin cells, leading to the overproduction of new skin cells, which accumulate to form the scales. There remains no cure, but several treatments are available for the symptoms, including topical steroids, light therapy and monoclonal antibodies that suppress the immune system.
A new monoclonal antibody, guselkumab, is being developed by Janssen as a potential psoriasis treatment. It is designed to target the p19 subunit of interleukins, making it specific for IL-23, and not the closely related IL-12 which is also blocked by the already approved antibody ustekinumab. IL-23 expression is raised in psoriatic lesions, and the theory is that blocking it could regulate T-cell counts and thus reduce the severity of symptoms.
In a randomised Phase I clinical trial, 24 patients with moderate to severe plaque psoriasis were given a single dose of placebo or 10, 30, 100 or 300mg of guselkumab.1 After 12 weeks, half of the subjects given 10mg, 60% of the 30mg and 100mg groups and all of those given 300mg doses had achieved a 75% improvement in psoriasis area and severity index (PASI) scores, whereas none of those given placebo had. The adverse event profile across all doses and placebo was similar.
Positive early results from a randomised, placebo- and active-comparator controlled parallel group dose-ranging Phase IIb trial were reported recently.2 A total of 293 patients with moderate to severe plaque psoriasis were randomised to receive subcutaneous injections of placebo, 5 or 100mg every eight weeks, 50 or 200mg at weeks 0, 4 and then every 12 weeks, or adalimumab. After 16 weeks, significantly more patients treated with guselkumab had achieved a 75% improvement in PASI score than those given adalimumab or placebo.
Subsequent to the 16 week assessment, the proportion of patients achieving these responses in the different guselkumab groups remained consistent or increased. Side-effect profiles were similar between the guselkumab and adalimumab groups.
1. H. Sofen et al. J. Allergy Clin. Immunol. 2014, 133, 1032
2. K. Callis-Duffin et al. J. Amer. Acad. Dermatol. 2014, 70, AB162, P8353