Icotyde (icotrokinra): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat moderate-to-severe plaque psoriasis in patients 12 years and older who weigh at least 40 kg and who are candidates for systemic therapy or phototherapyWording from FDA's list of novel approvals.
FDA review
Priority review
Company
Johnson & Johnson (Janssen)
Application
NDA 220149
Specialty
Dermatology
At a glance
Icotyde (icotrokinra) is an oral peptide that blocks the IL-23 receptor. It is approved for moderate-to-severe plaque psoriasis in patients 12 years and older who weigh at least 40 kg and are candidates for systemic therapy or phototherapy. In ICONIC-ADVANCE 1, clear or almost clear skin (IGA 0/1) at week 16 was reached by 68% with icotrokinra versus 11% with placebo, and it also beat deucravacitinib. There is no boxed warning, and adverse event rates were similar to placebo.
What it is and how it works
Icotrokinra is a peptide that binds the IL-23 receptor with high affinity and blocks IL-23 from binding. This reduces release of proinflammatory cytokines that depend on IL-23 signaling. Existing IL-23 blockers are monoclonal antibodies given by injection or infusion. Icotrokinra targets the same pathway at the receptor and is taken by mouth.
Phase 3, randomized, double-blind, placebo- and active-controlled trial across 149 sites in 13 countries. Placebo patients switched to icotrokinra at week 16 and deucravacitinib patients at week 24.
Co-primary end points at week 16 versus placebo: IGA 0/1 with at least a 2-grade improvement, and PASI 90.
Result
IGA 0/1: 68% vs 11%, difference 58% (95% CI 50 to 64), P<0.0001. PASI 90: 55% vs 4%, difference 51% (95% CI 44 to 57), P<0.0001.
Other results
Versus deucravacitinib, IGA 0/1 at week 16 was 68% vs 50% (difference 18%, 95% CI 11 to 26) and at week 24 was 74% vs 52%. PASI 90 at week 16 was 55% vs 30%, and at week 24 was 66% vs 41%. PASI 100 at week 16 was 31% vs 11%. Itch improvement at week 16 was 62% vs 17% with placebo. Responses were durable through week 52.
Safety in the trial
In the pooled ADVANCE trials, adverse events through week 16 occurred in 48% with icotrokinra and 57% with placebo. Nasopharyngitis and upper respiratory infection were the most common. Through week 24, adverse events were less frequent with icotrokinra than deucravacitinib (57% vs 65%).
How does Icotyde (icotrokinra) compare with the alternatives (Deucravacitinib, IL-23 inhibitor antibodies (guselkumab, risankizumab, tildrakizumab), IL-17 inhibitors (secukinumab, ixekizumab)) for moderate-to-severe plaque psoriasis in patients 12 years and older who weigh at least 40 kg and who are candidates for systemic therapy or phototherapy? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Co-primary end points at week 16 versus placebo: IGA 0/1 with at least a 2-grade improvement, and PASI 90.
Result
IGA 0/1: 70% vs 9%, difference 62% (95% CI 53 to 69), P<0.0001. PASI 90: 57% vs 1%, difference 56% (95% CI 48 to 62), P<0.0001.
Other results
Icotrokinra was superior to deucravacitinib on skin clearance at weeks 16 and 24. Responses were durable through week 52, with about 85% to 90% of week 16 responders maintaining response.
Safety in the trial
Safety was consistent with ADVANCE 1. No safety signals emerged through week 52.
There is no boxed warning. The label advises avoiding treatment during any clinically important active infection until it resolves. It also advises considering TB evaluation before starting, monitoring for active TB during and after treatment, and avoiding live vaccines. Immunizations should be completed before starting. In the 16-week pooled trials, serious infections occurred in 0.2% with icotrokinra and 0.4% with placebo. The most common adverse reactions (at least 1%) were headache, nausea, cough, fungal infection, and fatigue. One fatal upper gastrointestinal bleed occurred in a patient with underlying risk factors, and a link to the drug was not established.
What it competes with
Moderate-to-severe plaque psoriasis is treated with phototherapy or systemic agents, including oral small molecules, conventional immunosuppressants, and injectable biologics. Biologics are the main option for many patients with extensive disease.
DeucravacitinibOral TYK2 inhibitor. It was the active comparator in the pivotal trials.
IL-23 inhibitor antibodies (guselkumab, risankizumab, tildrakizumab)Injectable antibodies against the same pathway with established long-term data.
IL-17 inhibitors (secukinumab, ixekizumab)Injectable biologics with fast skin responses.
TNF inhibitors (adalimumab, etanercept)Older injectable biologics, also useful when psoriatic arthritis is present.
MethotrexateInexpensive conventional oral systemic agent that needs laboratory monitoring.
Bottom line for clinicians
Icotrokinra offers an oral option that targets IL-23 and showed higher skin clearance than the oral TYK2 inhibitor deucravacitinib through week 24. It suits patients who want a systemic therapy without injections. Weigh the lack of head-to-head data against injectable IL-23 antibodies, the need for infection and TB screening, and the limited long-term experience, which is currently about one year.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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