Icotrokinra: Research & Studies
Scientific evidence, clinical trials, and research findings
📌TL;DR
- •5 clinical studies cited
- •Overall evidence level: high
- •6 research gaps identified
Research Studies
Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents
Bissonnette R, Stein Gold L, Armstrong AW, et al. (2025) • New England Journal of Medicine
Phase 3 ICONIC-LEAD trial evaluating icotrokinra 200 mg once daily vs placebo in adults and adolescents with moderate-to-severe plaque psoriasis.
Key Findings
- 65% IGA 0/1 response with icotrokinra vs 8% placebo at week 16 (P<0.001)
- 50% PASI 90 response with icotrokinra vs 4% placebo at week 16 (P<0.001)
- Adverse events occurred in 49% of each group through week 16
- Most common adverse events were nasopharyngitis and upper respiratory tract infection
Limitations: Placebo-controlled comparison only through week 16; no direct comparison with injectable IL-23 inhibitors
An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis
Bissonnette R, Pinter A, Ferris LK, et al. (2024) • New England Journal of Medicine
Phase 2b FRONTIER 1 dose-finding trial of JNJ-77242113 at five dose levels vs placebo in adults with moderate-to-severe plaque psoriasis.
Key Findings
- 79% PASI 75 at week 16 with 100 mg BID vs 9% placebo
- Dose-dependent response across 25 mg QD to 100 mg BID range
- 45.2% achieved IGA 0 and 40.5% achieved PASI 100 at highest dose
- Safety profile comparable to placebo across all dose groups
Limitations: Phase 2b trial with relatively small per-group sample sizes; 16-week treatment period
Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2)
Stein Gold L, Armstrong AW, Bissonnette R, et al. (2025) • Lancet
Two Phase 3 trials comparing icotrokinra 200 mg QD with placebo and deucravacitinib 6 mg QD in moderate-to-severe plaque psoriasis.
Key Findings
- Icotrokinra met co-primary endpoints (IGA 0/1 and PASI 90) vs placebo at week 16
- Icotrokinra demonstrated superiority over deucravacitinib at weeks 16 and 24
- Safety profile consistent across all ICONIC trials
Limitations: Comparison with deucravacitinib rather than injectable IL-23 monoclonal antibodies
Targeted Oral Peptide Icotrokinra for Psoriasis Involving High-Impact Sites
Gooderham M, et al. (2025) • NEJM Evidence
Phase 3 ICONIC-TOTAL trial evaluating icotrokinra for psoriasis involving scalp, genital, hands, and feet in 311 participants.
Key Findings
- 56.7% overall IGA 0/1 with icotrokinra vs 5.8% placebo at week 16
- 65.9% scalp clearance (ss-IGA 0/1) vs 10.6% placebo
- 76.5% genital clearance (sPGA-G 0/1) vs 21.4% placebo
- Adverse events in 50% treatment vs 42% placebo
Limitations: Specialized population with high-impact site involvement; hand and foot psoriasis showed less dramatic separation from placebo
JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans
Fourie AM, Cheng X, Chang L, et al. (2024) • Scientific Reports
Preclinical and first-in-human characterization of JNJ-77242113 demonstrating high-affinity binding to IL-23R and oral bioavailability.
Key Findings
- KD of 7.1 pM for human IL-23R extracellular domain at 37 degrees C
- IC50 of 5.6 pM for IL-23-induced STAT3 phosphorylation in PBMCs
- Oral bioavailability demonstrated in rat models
- Selective for IL-23R with no activity against IL-12 or other cytokine receptors
Limitations: Preclinical study with limited human pharmacokinetic data from Phase 1
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🔍Research Gaps & Future Directions
- •Head-to-head comparison with injectable IL-23 inhibitors (guselkumab, risankizumab)
- •Long-term safety data beyond 52 weeks from extension studies
- •Efficacy and safety in pediatric patients under 12 years of age
- •Comparative efficacy in psoriatic arthritis
- •Real-world effectiveness and adherence data for oral vs injectable route
- •Biomarker predictors of treatment response
Research Overview#
Icotrokinra (JNJ-2113) has been evaluated in one of the most comprehensive clinical development programs for an oral peptide therapy, progressing from preclinical characterization through Phase 2b dose-finding to four pivotal Phase 3 trials. The evidence base includes publications in the New England Journal of Medicine, Lancet, and NEJM Evidence, establishing a high level of clinical evidence.
The evidence level is classified as high based on multiple Phase 3 randomized controlled trials with consistent results published in top-tier peer-reviewed journals. An NDA was submitted to the FDA in July 2025, supported by data from over 3,000 patients across the ICONIC clinical program.
ICONIC-LEAD Trial (Phase 3)#
Bissonnette et al., NEJM 2025 (PMID 41191940)#
The ICONIC-LEAD trial was the pivotal Phase 3, double-blind, randomized, placebo-controlled multicenter study evaluating icotrokinra in adults and adolescents (12 years and older) with moderate-to-severe plaque psoriasis.
Study Design:
- Participants randomized 2:1 to icotrokinra 200 mg once daily or placebo through week 16
- Placebo patients transitioned to icotrokinra at week 16
- Co-primary endpoints: PASI 90 and IGA 0/1 response at week 16
Key Results at Week 16:
| Endpoint | Icotrokinra | Placebo | P-value |
|---|---|---|---|
| IGA 0/1 | 65% | 8% | <0.001 |
| PASI 90 | 50% | 4% | <0.001 |
Safety: Adverse events occurred in 49% of each group through week 16, with nasopharyngitis and upper respiratory tract infection as the most common events in both groups.
FRONTIER 1 Trial (Phase 2b)#
Bissonnette et al., NEJM 2024 (PMID 38324484)#
This dose-finding trial established the dose-response relationship for icotrokinra across five regimens (25 mg QD, 25 mg BID, 50 mg QD, 100 mg QD, 100 mg BID) versus placebo in adults with moderate-to-severe plaque psoriasis.
Key Results at Week 16:
| Dose | PASI 75 | IGA 0 | PASI 100 |
|---|---|---|---|
| 25 mg QD | 37% | 10% | 10% |
| 25 mg BID | 58% | 26% | 23% |
| 50 mg QD | 56% | 17% | 14% |
| 100 mg QD | 73% | 37% | 34% |
| 100 mg BID | 79% | 45% | 41% |
| Placebo | 9% | 0% | 0% |
These results demonstrated clear dose-dependent efficacy, with the 100 mg BID dose achieving the highest response rates. The Phase 3 dose of 200 mg QD was selected based on pharmacokinetic modeling to provide comparable exposure.
ICONIC-ADVANCE 1 & 2 (Phase 3)#
Stein Gold et al., Lancet 2025 (PMID 40976249)#
These two identically designed Phase 3 trials were the first head-to-head comparisons of oral targeted therapies for psoriasis, comparing icotrokinra 200 mg QD with both placebo and deucravacitinib 6 mg QD (the only approved oral targeted therapy for moderate-to-severe psoriasis).
Key Findings:
- Icotrokinra met both co-primary endpoints (IGA 0/1 and PASI 90) vs placebo at week 16
- Icotrokinra demonstrated statistical superiority over deucravacitinib at both week 16 and week 24
- Safety profiles were consistent with the broader ICONIC program
ICONIC-TOTAL (Phase 3)#
Gooderham et al., NEJM Evidence 2025 (PMID 41191932)#
This trial specifically evaluated icotrokinra for psoriasis affecting high-impact body sites (scalp, genitals, hands, and feet) in 311 participants.
Key Results at Week 16:
| Body Site | Icotrokinra | Placebo |
|---|---|---|
| Overall (IGA 0/1) | 56.7% | 5.8% |
| Scalp (ss-IGA 0/1) | 65.9% | 10.6% |
| Genital (sPGA-G 0/1) | 76.5% | 21.4% |
Long-term extension data through week 52 showed further improvement, with 72% scalp clearance and 85% genital clearance.
Preclinical Characterization#
Fourie et al., Scientific Reports 2024 (PMID 39080319)#
This study provided the foundational pharmacological characterization of JNJ-77242113:
- Binding affinity: KD = 7.1 pM for human IL-23R (among the highest reported for any peptide-receptor interaction)
- Functional potency: IC50 = 5.6 pM for IL-23-induced STAT3 phosphorylation
- Selectivity: No cross-reactivity with IL-12 or other cytokine receptors
- Oral bioavailability: Demonstrated systemic exposure and pharmacodynamic activity following oral dosing in rats and humans
Evidence Quality Assessment#
| Criterion | Assessment | Details |
|---|---|---|
| Study design | Multiple Phase 3 RCTs | Four pivotal trials in ICONIC program |
| Sample size | Large (3,000+ patients) | Adequate for primary and subgroup analyses |
| Primary endpoints | Met in all trials | PASI 90, IGA 0/1 at week 16 |
| Active comparator | Yes (deucravacitinib) | Superiority demonstrated in ICONIC-ADVANCE |
| Safety database | Robust | Pooled data from entire ICONIC program |
| Peer-reviewed publication | Yes | NEJM (x2), Lancet, NEJM Evidence |
| Regulatory status | NDA submitted | FDA submission July 2025 |
Key Research Gaps#
-
Injectable comparisons: No head-to-head data vs injectable IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), which remain the efficacy benchmark.
-
Long-term safety: Extension study data beyond 52 weeks are still maturing. The long-term immunological consequences of sustained oral IL-23R blockade require ongoing surveillance.
-
Psoriatic arthritis: While IL-23 inhibitors have demonstrated efficacy in psoriatic arthritis, icotrokinra has not yet been evaluated in this indication.
-
Pediatric data: Clinical trials include adolescents aged 12+, but data in younger children are lacking.
-
Real-world adherence: Whether the convenience of oral dosing translates to improved adherence vs periodic injectable biologics remains to be determined.
Related Reading#
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Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.