Chemistry:Icotrokinra

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Icotrokinra, sold under the brand name Icotyde, is a medication used for the treatment of plaque psoriasis.[1] It is a cyclic peptide that functions as a selective interleukin 23 (IL-23) receptor antagonist.[2][3][4][5][6][7] It is being developed by Johnson & Johnson as an oral treatment for autoimmune disorders, including plaque psoriasis and ulcerative colitis.[8]

Icotrokinra was approved for medical use in the United States in March 2026.[9]

Medical uses

Icotrokinra is indicated for the treatment of moderate-to-severe plaque psoriasis in people aged twelve years of age and older who weigh at least 40 kilograms (88 lb) who are candidates for systemic therapy or phototherapy.[1]

Mechanism of action

Icotrokinra is a targeted oral peptide that selectively binds to and blocks the interleukin 23 receptor (IL-23R), thereby inhibiting IL-23-mediated signaling.[2][3] The drug demonstrates high affinity for the human IL-23 receptor with a dissociation constant (KD) of 7.1 pM and inhibits IL-23-induced STAT3 phosphorylation in peripheral blood mononuclear cells with an IC50 of 5.6 pM.[2][10] The IL-23 pathway plays a central role in the inflammatory cascade underlying various autoimmune conditions, particularly those involving Th17 cells.[3]

Unlike injectable biologics that target IL-23 or its receptor, icotrokinra offers the convenience of oral administration while maintaining selective receptor binding.[2][11][12]

Clinical trials

Plaque psoriasis

The clinical development program for plaque psoriasis includes several Phase III studies:

ICONIC-LEAD

The ICONIC-LEAD study is a Phase III, randomized, double-blind, placebo-controlled trial evaluating icotrokinra versus placebo in patients with moderate to severe plaque psoriasis.[13]

The study met its co-primary endpoints, with 74% of patients achieving clear or almost clear skin (IGA 0/1) at week 24.[13][14]

ICONIC-ADVANCE 1 and 2

The ICONIC-ADVANCE 1 and 2 studies are head-to-head Phase III trials comparing icotrokinra to deucravacitinib (Sotyktu) in patients with moderate to severe plaque psoriasis.[15] Both studies met their co-primary endpoints and demonstrated superiority of icotrokinra over deucravacitinib.[15][16][17]

ICONIC-TOTAL

The Phase 3 ICONIC-TOTAL study showed once daily icotrokinra met the primary endpoint of IGA of 0/1 at week 16 compared to placebo.[18]

Ulcerative colitis

ANTHEM-UC

The ANTHEM-UC study is a Phase IIb trial evaluating icotrokinra in adults with moderately to severely active ulcerative colitis.[19] The study met its primary endpoint of clinical response, with patients treated with the highest dose of icotrokinra achieving a response rate of 63.5% at week 12 versus 27% for placebo.[19]

Safety and tolerability

Across clinical studies, icotrokinra has demonstrated a favorable safety profile. In Phase III trials for plaque psoriasis, the most common adverse events were upper respiratory tract infections and headache.[13] Pooled safety data from multiple studies showed similar rates of adverse events between icotrokinra and comparator groups.[15]

History

Icotrokinra was jointly discovered by Johnson & Johnson (J&J) and Protagonist Therapeutics.[14][15]

References

  1. ↑ 1.0 1.1 Cite error: Invalid <ref> tag; no text was provided for refs named Icotyde FDA label
  2. ↑ 2.0 2.1 2.2 2.3 "Icotrokinra (JNJ-77242113) IL-23 Receptor Antagonist". https://www.medchemexpress.com/icotrokinra.html. 
  3. ↑ 3.0 3.1 3.2 "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". Scientific Reports 14 (1). Jul 2024. doi:10.1038/s41598-024-67371-5. PMID 39080319. Bibcode: 2024NatSR..1417515F. 
  4. ↑ "Psoriasis: a focus on upcoming oral formulations". Expert Opinion on Investigational Drugs 32 (7): 583–600. 3 July 2023. doi:10.1080/13543784.2023.2242767. PMID 37507233. 
  5. ↑ "S1028 Characterization of a First-in-Class Oral Therapy Selectively Targeting the IL-23 Pathway". American Journal of Gastroenterology 118 (10S): S781. October 2023. doi:10.14309/01.ajg.0000953752.29003.56. 
  6. ↑ "S1029 Disparities in Age, Sex, Race, and Ethnicity in Clinical Trials Focused on Inflammatory Bowel Disease in the United States". American Journal of Gastroenterology 118 (10S): S781–S782. October 2023. doi:10.14309/01.ajg.0000953756.85659.9e. 
  7. ↑ "Localised Delivery of Macromolecules to the Large Intestine: Translation to Clinical Trials". BioDrugs 36 (6): 687–700. November 2022. doi:10.1007/s40259-022-00562-6. PMID 36282433. 
  8. ↑ "Johnson & Johnson seeks first icotrokinra U.S. FDA approval aiming to revolutionize treatment paradigm for adults and adolescents with plaque psoriasis" (Press release). Johnson & Johnson. July 21, 2025.
  9. ↑ "FDA Approves Icotyde (icotrokinra) for the Treatment of Plaque Psoriasis". 2026-03-18. https://www.drugs.com/newdrugs/fda-approves-icotyde-icotrokinra-plaque-psoriasis-6748.html. 
  10. ↑ "Icotrokinra (JNJ-2113; JNJ-77242113; PN-235)". https://www.abmole.com/products/jnj-2113.html. 
  11. ↑ "Icotrokinra delivered an industry-leading combination of significant skin clearance with demonstrated tolerability in a once daily pill in Phase 3 topline results". JNJ (Press release). 2024-11-18. Archived from the original on 2024-11-23. Retrieved 2024-11-25.
  12. ↑ "Positive Phase 3 Results Announced for JNJ-2113 Treatment of Psoriasis". 2024-11-19. https://www.hcplive.com/view/positive-phase-3-results-announced-jnj-2113-treatment-psoriasis. 
  13. ↑ 13.0 13.1 13.2 "Icotrokinra delivered an industry-leading combination of significant skin clearance with demonstrated tolerability in a once daily pill in Phase 3 topline results" (Press release). Johnson & Johnson. July 18, 2025.
  14. ↑ 14.0 14.1 "A Study of JNJ-77242113 in Adolescent and Adult Participants With Moderate to Severe Plaque Psoriasis (ICONIC-LEAD)". https://clinicaltrials.gov/study/NCT06095115. 
  15. ↑ 15.0 15.1 15.2 15.3 "ICONIC-ADVANCE: Icotrokinra Beats Deucravacitinib for Plaque Psoriasis". 2025-09-19. https://www.hcplive.com/view/iconic-advance-icotrokinra-bests-deucravacitinib-for-plaque-psoriasis. 
  16. ↑ "A Study of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis". https://clinicaltrials.gov/study/NCT06143878. 
  17. ↑ "A Study of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis (ICONIC-ADVANCE 2)". https://clinicaltrials.gov/study/NCT06220604. 
  18. ↑ "A Study of JNJ-77242113 for the Treatment of Participants With Plaque Psoriasis Involving Special Areas (ICONIC-TOTAL)". https://clinicaltrials.gov/study/NCT06095102. 
  19. ↑ 19.0 19.1 "Icotrokinra meets primary endpoint of clinical response in ulcerative colitis study and shows potential to transform the treatment paradigm for patients" (Press release). Johnson & Johnson. March 10, 2025.



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