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The first oral peptide to block a cytokine receptor — biologic-level psoriasis clearance from a once-daily pill.
Also known as: JNJ-77242113 · JNJ-2113 · PN-21235 · Icotyde (brand)
Part of the Foundational & therapeutic peptides cluster
Overview
Icotrokinra (JNJ-77242113) is an orally bioactive macrocyclic peptide that selectively binds the interleukin-23 receptor and blocks its signalling. In phase 3 trials 65–70% of adults and adolescents with moderate-to-severe plaque psoriasis reached clear or almost-clear skin at 16 weeks versus 8–11% on placebo, with adverse-event rates matching placebo. The FDA approved it in March 2026.
Source & context
Biological / chemical source: Synthetic macrocyclic peptide with a Val1–Val6 disulfide bridge and N-terminal acetylation (Johnson & Johnson / Protagonist)
Primary research or clinical context: Approved (FDA, March 2026) for moderate-to-severe plaque psoriasis; phase 3 in psoriatic arthritis and ulcerative colitis, phase 2/3 in Crohn's disease
What icotrokinra is
Icotrokinra (JNJ-77242113, earlier JNJ-2113 and PN-21235) is an orally bioactive peptidic antagonist of the IL-23 receptor (IUPHAR ligand 14181). It was advanced to trials in inflammatory autoimmune conditions including psoriasis and ulcerative colitis, reported superior efficacy to placebo and to the TYK2 inhibitor deucravacitinib in phase 3 psoriasis studies in 2025, and received its first approval from the US FDA in March 2026 for moderate-to-severe plaque psoriasis (IUPHAR clinical-use record). It is described as a first-in-class, orally administered macrocyclic peptide that selectively targets IL-23R (Ferreira & Torres, American Journal of Clinical Dermatology 2026).
Mechanism
IL-23 drives the Th17 pathway central to psoriasis, and injected antibodies against IL-23 or its p19 subunit set the current efficacy benchmark. Icotrokinra blocks the same axis from the receptor side: it selectively binds IL-23R and inhibits downstream signalling (Knight et al., Dermatology and Therapy 2025). A phase 2b pharmacodynamic study showed early and sustained responses in psoriasis (Strawn et al., JCI Insight 2025). Available oral agents for psoriasis had offered limited potency or tolerability; an oral therapy with biologic-like efficacy was the unmet need (Ferreira & Torres, 2026).
Structure and oral delivery
The IUPHAR record notes a disulfide bond between Val1 and Val6 and other modifications; PubChem's name for the compound lists N-acetylation, non-natural residues such as 7-methyl-tryptophan, 2-naphthylalanine and 3-pyridylalanine, and a cyclic (1→6) disulfide. Its formula is C90H120N20O22S2 and its mass about 1,898 Da (PubChem CID 162462321). Oral bioavailability was 0.1–0.3% in animals, with evidence of systemic exposure sufficient for target engagement (Knight et al., 2025) — a peptide designed to act despite, not because of, high absorption.
Clinical evidence: ICONIC-LEAD
In the phase 3 ICONIC-LEAD trial, 684 adults and adolescents (≥12 years) with moderate-to-severe plaque psoriasis were randomised 2:1 to icotrokinra 200 mg once daily or placebo. At week 16, 65% of icotrokinra recipients versus 8% on placebo had an IGA 0/1 response, and 50% versus 4% reached PASI 90 (P<0.001 for both); complete clearance was 33% versus 1% (IGA 0) and 27% versus under 1% (PASI 100). Adverse events occurred in 49% of each group, most commonly nasopharyngitis and upper respiratory tract infection (Bissonnette et al., New England Journal of Medicine 2025).
| Endpoint | Icotrokinra 200 mg daily | Placebo |
|---|---|---|
| IGA 0/1 (clear / almost clear) | 65% | 8% |
| PASI 90 | 50% | 4% |
| IGA 0 (complete clearance) | 33% | 1% |
| PASI 100 | 27% | <1% |
| Any adverse event | 49% | 49% |
ICONIC-ADVANCE 1 and 2: versus deucravacitinib
Two further phase 3 trials compared icotrokinra with placebo and with the oral TYK2 inhibitor deucravacitinib. IGA 0/1 at week 16 was reached by 68% and 70% of icotrokinra participants versus 11% and 9% on placebo, and PASI 90 by 55% and 57% versus 4% and 1%; all co-primary endpoints were met. Adverse-event rates to week 16 were 48% with icotrokinra and 57% with placebo, and to week 24 were 57% with icotrokinra versus 65% with deucravacitinib (Gold et al., Lancet 2025). A separate phase 3 trial addressed psoriasis at high-impact sites — scalp, genitals, hands and feet (Gooderham et al., NEJM Evidence 2025).
Beyond psoriasis
ClinicalTrials.gov lists phase 3 trials in psoriatic arthritis in biologic-naïve and biologic-experienced patients (NCT06878404, NCT06807424), a phase 3 programme in ulcerative colitis (NCT07196748) and a phase 2/3 study in Crohn's disease (NCT07196722) as of September 2026. Oral peptide therapeutics are described as an emerging modality across immune-mediated inflammatory diseases (Stein Gold et al., Advances in Therapy 2025). The lactation database notes its 1,898-Da mass makes milk excretion unlikely (LactMed).
Why it belongs in a peptide directory
Icotrokinra is the clearest demonstration that a peptide can be made orally active against a target usually reserved for antibodies. Its relatives in this directory are the other approved macrocycles (zilucoplan) and the oral incretin story told on the orforglipron comparison guide. This page is educational and not treatment guidance.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Macrocyclic peptide with a disulfide bond between Val1 and Val6 and other non-natural modifications (IUPHAR record)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C90H120N20O22S2
- Average reference mass
- ≈ 1,898.2
- Receptors
- Interleukin-23 receptor (IL-23R) — selective antagonist
- Backbone
- Macrocyclic peptide with a disulfide bond between Val1 and Val6 and other non-natural modifications (IUPHAR record)
- Status
- Approved: FDA (March 2026) for moderate-to-severe plaque psoriasis
Disulphide bond Val<sup>1</sup>-Val<sup>6</sup>, and other modifications
- PubChem CID: 162462321
- IUPHAR ligand: 14181
- CAS RN: 2763602-16-8
- UNII: MUW8FP7HNZ
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 4 registered studies with “Icotrokinra” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06878404 | A Study to Evaluate the Efficacy and Safety of JNJ-77242113 (Icotrokinra) in Biologic-naïve Participants With | Phase 3 | active not recruiting | 2026-09-25 |
| NCT07196748 | A Protocol of Icotrokinra Therapy in Adult and Adolescent Participants With Moderately to Severely Active Ulce | Phase 3 | recruiting | 2026-09-25 |
| NCT07196722 | A Study of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease | Phase 3 | recruiting | 2026-09-25 |
| NCT06807424 | A Study to Evaluate the Efficacy and Safety of Icotrokinra (JNJ-77242113) in Biologic-experienced and Biologic | Phase 3 | recruiting | 2026-09-25 |
Icotrokinra — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Macrocyclic peptide with a disulfide bond between Val1 and Val6 and other non-natural modifications (IUPHAR record)Average reference mass: 1,898.2 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 14181 and PubChem CID 162462321.
- TrialsClinicalTrials.gov snapshot added: 4 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Icotrokinra
What is Icotrokinra?+
Icotrokinra (JNJ-77242113) is an orally bioactive macrocyclic peptide that selectively binds the interleukin-23 receptor and blocks its signalling. In phase 3 trials 65–70% of adults and adolescents with moderate-to-severe plaque psoriasis reached clear or almost-clear skin at 16 weeks versus 8–11% on placebo, with adverse-event rates matching placebo. The FDA approved it in March 2026.
What Canadian product status is recorded for Icotrokinra?+
Canadian product status for Icotrokinra has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Icotrokinra?+
Icotrokinra is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is icotrokinra?+
An oral macrocyclic peptide (JNJ-77242113) that selectively blocks the IL-23 receptor. The FDA approved it in March 2026 for moderate-to-severe plaque psoriasis.
How effective is icotrokinra for psoriasis?+
In ICONIC-LEAD, 65% of participants reached clear or almost-clear skin at 16 weeks versus 8% on placebo, and 27% reached complete clearance (PASI 100).
Is icotrokinra a pill?+
Yes — a once-daily 200 mg oral tablet in the phase 3 trials, despite oral bioavailability of only 0.1–0.3% in animal studies.
How does icotrokinra compare with deucravacitinib?+
In ICONIC-ADVANCE 1 and 2 it showed superior clinical response rates to deucravacitinib, with lower adverse-event rates to week 24 (57% vs 65%).
Related peptides
References & further reading
- 1.Bissonnette et al. (2025). Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents. New England Journal of Medicine
- 2.Gold et al. (2025). Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2). Lancet
- 3.Knight et al. (2025). Translational Pharmacokinetics of Icotrokinra, a Targeted Oral Peptide that Selectively Blocks Interleukin-23 Receptor and Inhibits Signaling. Dermatology and Therapy
- 4.Ferreira & Torres (2026). Icotrokinra: An Oral Interleukin-23 Receptor Antagonist Peptide for the Treatment of Psoriasis. American Journal of Clinical Dermatology
- 5.Gooderham et al. (2025). Targeted Oral Peptide Icotrokinra for Psoriasis Involving High-Impact Sites. NEJM Evidence
- 6.Stein Gold et al. (2025). Oral Peptide Therapeutics as an Emerging Treatment Modality in Immune-Mediated Inflammatory Diseases. Advances in Therapy
- 7.PubChem — compound summary for Icotrokinra (CID 162462321)