IL-23 Blockade Goes Oral Save

A new player is entering the IL-23 arena — and it’s a tablet! Icotrokinra (ICO), a first-in-class peptide that binds and blocks the interleukin-23 receptor (IL-23R), is showing encouraging efficacy and safety across a range of psoriasis (PSO) and psoriatic disease (PsD) studies.

Results of a RCT of ICO in PsD were presented in Abstract #0555. ICONIC-TOTAL was a Phase 3 “basket-like” study, broadened the view to psoriasis at challenging sites — scalp, genital, and hand/foot. ICO 200 mg once daily significantly outperformed placebo for overall skin clearance (IGA 0/1 57% vs 6%) and site-specific endpoints (e.g., scalp IGA 0/1 66% vs 11%; genital IGA 0/1 77% vs 21%). Nasopharyngitis was the most common AE, with GI events <8% — a reassuring safety signal for an oral systemic therapy.

In Abstract #0875, presented by Dr Merola, the ICONIC-LEAD Phase 3 trial shows promising data in adolescent with PSO. Following the publication of ICONIC ADVANCE 1&2, in the LANCET last month, showing superiority of ICO compared to both PBO and Deucravacitinib; ICO became the first systemic therapy tested simultaneously in adolescents and adults with moderate-to-severe PSO. By Week 16, adolescents on ICO achieved high clearance or near clearance rates (IGA 0/1 84% vs 27% placebo; PASI 90 71% vs 14%), maintained through Week 24 — all with reassuring safety profile, and no new signals.

Meanwhile, in Abstract #0562 exploratory analyses from FRONTIER 1, the Phase 2 ICO PSO RCT, looked at patients with concomitant PsA. ICO’s pharmacodynamic effects on serum BD-2, IL-22, and IL-17 cytokines were consistent between PsO and PsO+PsA subsets. Treated patients reported meaningful improvements in PROMIS-29 domains related to pain, fatigue, and physical function. These translational data, along with modelling that bridged PASI75 to ACR20, supported the design of the ongoing ICONIC-PsA 1 and 2 trials — large global Phase 3 studies aiming to confirm efficacy of ICO in PsA across diverse populations.

In summary, ICO represents an exciting next step — a targeted, oral IL-23R inhibitor with early proof of robust efficacy, durable skin clearance, and a favourable safety profile in PSO. For both dermatology and rheumatology, the “new kid on the block” sounds promising and now hoping to see the results of the PsA 1&2 RCTs soon.