Novel biologic therapies in development targeting IL-12/IL-23

Abstract

Recent research has identified the importance of interleukin 12 (IL)-12 and IL-23 in the immunopathogenesis of psoriasis. The p40 subunit common to IL-12 and IL-23 is an attractive target for selective therapy. Clinical study data are available for two anti-IL-12/23 therapies: ustekinumab (CNTO 1275, approved in 2009 for treatment of plaque psoriasis) and ABT-874. The Phase 3 clinical trials PHOENIX 1 and PHOENIX 2 have shown significant benefit for ustekinumab in moderate-to-severe plaque psoriasis, with PASI 75 response rates ranging from 66% at week 12 (after two injections) and rising to 85% at week 24 (after three injections). Withdrawal of treatment led to a gradual return of psoriasis whereas continued therapy every 12 weeks with ustekinumab maintained PASI 75 response. Analysis of safety data demonstrated a safety profile similar to placebo at week 12 and did not reveal any major safety concerns in blocking IL-12 and IL-23 for periods as long as 18 months. Phase 2 data indicate that ABT-874 is also efficacious in the treatment of moderate-to-severe plaque psoriasis across a range of dosing strategies.