First-in-Class Oral IL-23 Receptor Blocker Icotrokinra Achieves 65% Skin Clearance in Phase 3 Psoriasis Trial
View StudyPlain-Language Summary
A phase 3 clinical trial published in the New England Journal of Medicine found that icotrokinra, the first oral peptide to selectively block the interleukin-23 receptor, achieved significant skin clearance in adults and adolescents with moderate-to-severe plaque psoriasis. At 16 weeks, 65% of patients receiving icotrokinra had an IGA score of 0 or 1 (clear or almost clear skin), compared to just 8% of those on placebo. The FDA has since approved icotrokinra under the brand name ICOTYDE, making it the first oral first-line systemic therapy for plaque psoriasis approved in adults and adolescents aged 12 and older.
Abstract
Plaque psoriasis is a chronic immune-mediated skin disease driven substantially by the interleukin-23/interleukin-17 axis. Existing systemic therapies include conventional agents such as methotrexate, injectable biologics targeting IL-17A, IL-17A/F, IL-23, and TNF, and oral small molecules such as apremilast and deucravacitinib. While biologic therapies have transformed outcomes in moderate-to-severe disease, they require injection and are associated with immunosuppressive effects. Icotrokinra is a first-in-class oral peptide that selectively binds and blocks the interleukin-23 receptor, inhibiting downstream Th17 and Th22 inflammatory signaling with the potential for greater target selectivity than small-molecule JAK inhibitors.
The ICONIC-LEAD trial was a phase 3, randomized, double-blind, placebo-controlled study enrolling 684 adults and adolescents (aged 12 years and older) with moderate-to-severe plaque psoriasis across multiple international centers. Participants were randomized 2:1 to receive icotrokinra 200 mg once daily (n=456) or placebo (n=228) for 16 weeks, after which all placebo participants were transitioned to icotrokinra through week 24. Coprimary endpoints were the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline, and a 90% or greater reduction in the Psoriasis Area and Severity Index (PASI 90) score at week 16.
Icotrokinra met both coprimary endpoints with highly statistically significant results. IGA 0/1 was achieved in 65% of icotrokinra-treated patients versus 8% of placebo patients (p less than 0.0001), and PASI 90 was achieved in 50% versus 4% (p less than 0.0001). The safety profile was acceptable, with adverse event rates similar between treatment arms and no new safety signals identified. These results supported FDA approval of icotrokinra (ICOTYDE) as the first targeted oral peptide for moderate-to-severe plaque psoriasis in adults and adolescents.