A once-daily pill has matched the effectiveness of injectable biologics for psoriasis, potentially transforming how millions of patients manage their condition.
A once-daily pill has matched the effectiveness of injectable biologics for psoriasis, potentially transforming how millions of patients manage their condition. Icotrokinra, the first oral medication to block the IL-23 receptor, achieved clear or almost clear skin in 74% of patients after 24 weeks in pivotal trials—results that rival current injectable treatments while offering the convenience of a daily tablet.
This breakthrough matters because it addresses a fundamental treatment gap. Despite highly effective injectable biologics being available for over a decade, the majority of eligible psoriasis patients never receive advanced therapies. Many cite injection anxiety, inconvenience, or storage requirements as barriers. Johnson & Johnson’s new drug, developed with Protagonist Therapeutics, could finally bridge the chasm between topical creams and injectable biologics, offering patients a middle ground they’ve long sought.
The drug represents a technical achievement as well—oral peptides typically break down in the digestive system before reaching their targets. Scientists engineered icotrokinra as an approximately 1.9 kDa macrocyclic peptide that survives digestion and maintains single-digit picomolar affinity for its receptor. With an FDA decision expected by mid-2026, this innovation could reshape treatment approaches for the 8 million Americans living with psoriasis.
The science of selective IL-23 blockade made simple
Understanding how icotrokinra works requires grasping why IL-23 matters in psoriasis. This inflammatory signaling molecule acts like a master switch for the immune cascade that drives psoriatic plaques. By binding to the IL-23 receptor on immune cells, icotrokinra prevents this inflammatory signal from triggering the downstream effects that cause red, scaly skin patches.
What sets icotrokinra apart is its selectivity. While older biologics like ustekinumab block both IL-12 and IL-23 through their shared subunit, icotrokinra targets only IL-23. This precision potentially reduces off-target effects while maintaining therapeutic efficacy. The drug’s oral bioavailability—achieved without special formulation enhancers—marks a significant advance in peptide drug design.
The molecular engineering behind this achievement involved creating a cyclic structure with a disulfide bond, achieving picomolar binding affinity that enables therapeutic efficacy despite oral delivery challenges. This potency allows effective dosing despite the challenges of oral delivery, where stomach acid and digestive enzymes typically destroy peptide drugs before they can act.
Clinical trials reveal consistent excellence across patient groups
The ICONIC clinical program enrolled over 1,000 patients across four Phase 3 studies, generating an unusually robust dataset for regulatory submission. In the flagship ICONIC-LEAD trial, 684 participants with moderate-to-severe plaque psoriasis received either icotrokinra or placebo for 24 weeks.
The results exceeded expectations. At week 16, 65% of icotrokinra patients achieved an Investigator’s Global Assessment (IGA) score of 0 or 1, indicating clear or almost clear skin, compared to just 8% on placebo. More impressively, efficacy continued improving through week 24, when 74% reached this milestone. Nearly half the patients—46%—achieved completely clear skin, a outcome many thought impossible with oral therapy.
Adolescent patients showed even stronger responses. Among 66 participants aged 12 and older, 86% achieved clear or almost clear skin by week 24, with 75% reaching complete clearance. These results suggest younger patients may respond particularly well to oral IL-23 blockade, offering hope for early intervention in psoriasis management.
The ICONIC-ADVANCE trials took the unprecedented step of directly comparing icotrokinra to deucravacitinib (Sotyktu), an existing oral therapy. Icotrokinra demonstrated statistical superiority at both 16 and 24 weeks, establishing a new efficacy benchmark for oral psoriasis treatments. The ICONIC-TOTAL study focused on notoriously difficult-to-treat areas—scalp, genitals, hands, and feet—meeting its primary endpoints and confirming efficacy across all body regions.
Safety profile mirrors placebo in extensive testing
Across the pooled Phase 3 data, icotrokinra’s safety profile proved remarkably benign. Adverse events occurred in 49% of icotrokinra patients versus 52% receiving placebo, with no new safety signals emerging despite extensive monitoring. Serious adverse events remained rare and occurred at similar rates between groups.
This favorable tolerability distinguishes icotrokinra from some existing therapies. Oral medications like apremilast often cause gastrointestinal side effects that lead to discontinuation. Injectable biologics can trigger injection site reactions and require monitoring for infections. Icotrokinra’s placebo-like tolerability could improve long-term adherence, crucial for a chronic condition requiring continuous treatment.
The safety data gains additional significance given the drug’s novel mechanism. As the first oral IL-23 receptor antagonist, icotrokinra faced heightened scrutiny for unexpected effects. The clean safety profile across diverse patient populations, including adolescents, supports its potential as a first-line advanced therapy.
Redefining treatment pathways for moderate-to-severe disease
Where icotrokinra fits in the psoriasis treatment arsenal depends on perspective. For patients, the drug offers liberation from injections while maintaining high efficacy. Surveys indicate over 50% of dermatologists would prescribe icotrokinra as first-line advanced systemic therapy, suggesting rapid adoption upon approval.
The efficacy comparisons to injectable biologics reveal nuanced positioning. While icotrokinra may not match the 90% skin clearance rates of leading IL-23 inhibitors like risankizumab or guselkumab, it appears roughly comparable to ustekinumab, a blockbuster biologic that generated over $10 billion in 2024 sales. This positions icotrokinra as highly effective without claiming best-in-disease status.
For the healthcare system, oral therapy could expand treatment access. Injectable biologics require patient training, cold-chain shipping, and often specialty pharmacy coordination. A room-temperature stable pill simplifies logistics while potentially reducing overall treatment costs despite premium pricing. Insurance coverage decisions will prove critical—oral formulations sometimes face different coverage criteria than injectables.
The ongoing ICONIC-ASCEND study, comparing icotrokinra head-to-head with injectable ustekinumab, will provide definitive positioning data. Results expected in 2026 could establish whether convenience comes at any efficacy cost or if oral delivery matches injection performance.
Beyond skin deep: expanding indications strengthen the pipeline
Icotrokinra’s potential extends well beyond psoriasis. The Phase 2b ANTHEM-UC trial in ulcerative colitis delivered compelling results in March 2025, with 64% of patients achieving clinical response versus 27% on placebo. Clinical remission rates of 30% at week 12, improving through week 28, suggest durable benefit in inflammatory bowel disease.
Phase 3 trials in psoriatic arthritis launched in 2025, targeting the quarter of psoriasis patients who develop joint involvement. Success here would position icotrokinra as a comprehensive treatment for psoriatic disease, addressing both skin and joint manifestations with convenient oral dosing. The IL-23 pathway’s role in multiple inflammatory conditions opens possibilities for Crohn’s disease and other autoimmune disorders.
Johnson & Johnson projects peak annual sales exceeding $5 billion, reflecting confidence in multi-indication potential. Even conservative forecasts from GlobalData predict $2.2 billion by 2030, achieving blockbuster status by 2029. The Protagonist Therapeutics partnership has already generated $165 million in milestone payments, with up to $630 million additional payments possible plus tiered royalties reaching 10% of sales.
Transforming daily life for millions living with psoriasis
The human impact of effective oral therapy cannot be overstated. Psoriasis affects 125 million people worldwide, with moderate-to-severe disease dramatically impacting quality of life. Beyond visible symptoms, patients face employment discrimination, relationship challenges, and mental health struggles. The prospect of normal-appearing skin achieved through daily pills rather than periodic injections represents profound progress.
Treatment adherence remains a persistent challenge in psoriasis management. Complex injection schedules, cold storage requirements, and injection anxiety all contribute to suboptimal outcomes. A once-daily pill taken with morning coffee eliminates these barriers, potentially improving long-term disease control through better adherence.
For adolescents, who showed exceptional response rates in trials, oral therapy offers particular advantages. Young patients often struggle with injection anxiety and the social stigma of visible injection supplies. Discreet oral medication could improve treatment acceptance during crucial developmental years.
As healthcare evolves toward patient-centered models, icotrokinra exemplifies innovation addressing real-world needs. The drug doesn’t just offer incremental improvement—it reimagines how patients experience treatment, removing friction points that have limited optimal care delivery for decades.
Conclusion
Icotrokinra stands poised to reshape psoriasis treatment by delivering injectable-class efficacy in an oral formulation. The compelling Phase 3 data, favorable safety profile, and superiority over existing oral options position it for rapid adoption following anticipated FDA approval in 2026. While questions remain about long-term outcomes and comparative efficacy versus leading injectable biologics, the fundamental advance—effective oral IL-23 blockade—marks a watershed moment in dermatology.
The broader implications extend beyond convenience. By lowering barriers to advanced therapy, icotrokinra could help millions of undertreated patients achieve clear skin for the first time. The successful oral peptide platform validates new approaches to drug delivery, with Protagonist Therapeutics already advancing additional oral biologics. As precision medicine advances, icotrokinra demonstrates that innovation isn’t just about new targets—it’s about making proven mechanisms accessible in ways that transform patient experience.
For patients living with psoriasis, healthcare providers managing complex cases, and industry observers tracking pharmaceutical innovation, icotrokinra represents the convergence of scientific achievement and patient-centered design. The wait for FDA approval may feel long for those eager to offer or receive this therapy, but the data suggest it will prove worth it. In a field where incremental advances often pass for innovation, icotrokinra delivers genuine transformation—proof that sometimes, the best new drug is one that makes proven science more human.
Disclaimer
Important Notice: Icotrokinra is an investigational drug that has not yet been approved by the U.S. Food and Drug Administration (FDA) or other regulatory agencies. This article is for informational and educational purposes only and should not be considered medical advice, diagnosis, or treatment recommendations.
Medical Consultation Required: Patients with psoriasis or other conditions should consult with qualified healthcare professionals before making any treatment decisions. Individual results may vary, and what works for clinical trial participants may not be suitable for all patients.
Clinical Trial Data: The efficacy and safety information presented is based on clinical trial results reported by Johnson & Johnson and Protagonist Therapeutics. These results may not reflect real-world outcomes, and long-term effects are still being studied.
No Financial Relationship: This article is written for informational purposes and does not constitute an endorsement of any specific treatment or company. The author has no financial relationship with Johnson & Johnson, Protagonist Therapeutics, or any other pharmaceutical companies mentioned.
Current Treatment Options: Patients currently receiving psoriasis treatment should not discontinue their medications based on this article. Multiple effective treatments are currently available, and treatment decisions should always be made in consultation with healthcare providers familiar with individual medical histories.
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