Phase 3 Findings Suggest Icotrokinra Effective in Adults, Adolescents with Psoriasis

Icotrokinra therapy may result in high rates of clear/almost clear skin and relief from symptoms of moderate-to-severe psoriasis, new findings suggest, with no new safety signals identified through 24 weeks of use.¹

These recent findings from the ICONIC-LEAD study were presented in poster format at the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference, in Las Vegas, Nevada. This poster was authored by such investigators as Robert Bissonnette, MD, chairman at Innovaderm Research in Montreal, Canada.

“These study results are promising, showing the potential for icotrokinra to offer patients the unique combination of complete skin clearance and a favorable safety profile in a once-daily pill,” Bissonnette said in a previous interview with HCPLive.²

Bissonnette and coauthors highlighted the background of ICONIC-LEAD, noting that patients with moderate-to-severe psoriasis typically limited to injectable options to attain a high-level of efficacy with a safety profile that is favorable. Icotrokinra, Bissonnette et al highlighted, is a first-in-class, targeted oral peptide that selectively binds the interleukin (IL)-23 receptor and is designed to inhibit IL-23 pathway signaling.¹

The investigators noted that the multicenter study had a randomized, double-blind, placebo-controlled design. The study had involved 684 participants aged 12 years and older, recruiting such patients at 170 sites around the world. Criteria for elligibility included having a body surface area (BSA) involvement of 10% at minimum, a Psoriasis Area and Severity Index (PASI) score of 12 or greater, and an Investigator’s Global Assessment (IGA) score of 3 or more.

Participants were randomized in a 2:1 ratio to receive be treated with icotrokinra 200 mg QD through the 24-week mark or placebo through the 16-week mark, after which those in the placebo arm transitioned to treatment with this medication. Bissonnette and coauthors’ co-primary endpoints at the 16-week mark were a PASI 90 response and the proportion of subjects with an IGA score of 0 or 1, with a minimum 2-grade improvement from baseline. The latter score would indicate clear or almost clear skin.

A total of 684 individuals were randomized—456 to the treatment arm and 228 to the placebo arm. Significantly more of those on icotrokinra at 16 weeks reached the co-primary endpoints compared to subjects in the placebo cohort.¹ Specifically, the investigative team found that 65% of those in the icotrokinra cohort attained IGA 0/1 compared to only 8% of those given a placebo.

Additionally, they concluded that 50% achieved PASI 90 versus just 4% in the placebo arm (both P < .001). The team also noted complete skin clearance was seen more frequently among those on icotrokinra, with 33% attaining an IGA score of 0 and 27% a PASI 100 score, versus 1% and less than 1%, respectively, in the placebo group (both multiplicity-adjusted P < .001).

Continued efficacy was observed by Bissonnette to improve with ongoing use of the drug through the 24-week mark. At this point in time, 74% of those on icotrokinra achieved IGA 0/1, with 65% reaching PASI 90, 46% reporting IGA 0, and 40% showing a PASI 100 score.

In terms of safety, the investigators noted the comparability of rates of adverse events (AEs) between groups over the first 16 weeks. Specifically, 49% in both the icotrokinra and placebo arms showed at least a single AE. The most common ones were found to be nasopharyngitis and upper respiratory tract infections.

Bissonnette and colleagues also found that gastrointestinal-related side effects were seen in 6% of patients in both cohorts. Overall, however, a lack of new safety concerns were identified through Week 24.

References

1. Bissonnette R, Soung J, Lebwohl M, et al. Icotrokinra, a Targeted Oral Peptide That Selectively Blocks the Interleukin-23-Receptor, for the Treatment of Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3, Randomized, Double-Blind, Placebo-Controlled ICONIC-LEAD Trial. Presented at DERM 2025 NP PA CME Conference; July 23-26, 2025; Las Vegas, Nevada.

2. Bissonnette R. Icotrokinra, Plaque Psoriasis, and ICONIC-LEAD, with Robert Bissonnette, MD. HCPLive. March 8, 2025. Accessed August 8, 2025. https://www.hcplive.com/view/icotrokinra-plaque-psoriasis-and-iconic-lead-with-robert-bissonnette-md.