Oral Icotrokinra Sustains Clear/Almost Clear Skin in Plaque Psoriasis for One Year

Plaque psoriasis is a chronic inflammatory skin condition significantly impacting quality of life. Current biologic therapies, while effective, often require parenteral administration, carry high costs, and necessitate frequent monitoring, posing adherence challenges for patients. This creates a need for more convenient, oral treatment options that maintain high efficacy. Icotrokinra is an investigational oral peptide designed to precisely block the interleukin-23 receptor (IL-23R), a key cytokine pathway implicated in the pathogenesis of psoriasis. Its oral delivery and targeted mechanism offer a potential advantage over existing treatments.

Two Phase 3, randomized, placebo- and active comparator-controlled trials, ICONIC-ADVANCE 1 & 2, enrolled 1505 adults with moderate-to-severe plaque psoriasis (body surface area ≥10%, PASI ≥12, IGA ≥3). Participants were randomized (2:1:2 or 4:1:4) to receive icotrokinra 200 mg once daily, placebo (transitioned to icotrokinra at Week 16), or deucravacitinib 6 mg once daily (transitioned to icotrokinra at Week 24). Outcomes through Week 52 included proportions achieving IGA 0/1 (clear/almost clear skin), PASI 90, IGA 0, PASI 100, ss-IGA 0/1, and patient-reported outcomes like PSSD itch CMI (≥4-point reduction) and DLQI 0/1. Adverse events (AEs) were also monitored.

Across both studies, skin clearance rates for icotrokinra-randomized participants steadily increased through Week 24 and demonstrated remarkable durability through Week 52. Response rates for scalp-specific IGA 0/1 and various patient-reported outcomes, including PSSD itch CMI and DLQI 0/1, also showed sustained durability through Week 52. > Approximately 70%-75% of participants exhibited clear or almost clear skin, achieving IGA 0/1 or PASI 90 during Weeks 24-52, with about 50% achieving completely clear skin (IGA 0 or PASI 100).

• Among those who achieved clear/almost clear skin at Week 16, a high proportion of ~85%-90% maintained this robust response at Week 52. Participants initially on placebo or deucravacitinib who transitioned to icotrokinra subsequently exhibited increasing response rates that became comparable to those randomized to icotrokinra from the start, further supporting its efficacy. The adverse event profile of icotrokinra was found to be similar to that of placebo.