Icotrokinra Shows Promise for Moderate-to-Severe Plaque Psoriasis in Phase 3 Trials

Robert Bissonnette, MD

© International Psoriasis Council

Johnson & Johnson announced positive new data from the Phase 3 ICONIC-LEAD trial examining icotrokinra (JNJ-2113), a first-in-class investigational targeted oral peptide that selectively blocks the interleukin-23 (IL-23) receptor in patients with moderate-to-severe plaque psoriasis (PsO), according to a news release and late-breaking news from the 2025 American Academy of Dermatology Conference in Orlando.¹

Icotrokinra is being studied in adults and adolescents aged ≥12 years with moderate-to-severe plaque PsO. In the ICONIC-LEAD trial, once-daily icotrokinra demonstrated robust skin clearance and a favorable safety profile at Week 16 compared with placebo in 684 participants. Notable outcomes included:

• IGA 0/1 (Clear or Almost Clear Skin): 65% with icotrokinra vs 8% with placebo (P<.001)
• PASI 90: 50% with icotrokinra vs 4% with placebo (P<.001)¹

Continued improvement in skin clearance was observed at Week 24, with 74% of icotrokinra-treated patients achieving IGA 0/1 and 65% achieving PASI 90. Nearly half (46%) of icotrokinra-treated patients reached IGA 0 (completely clear skin) by Week 24, and 40% achieved PASI 100. The incidence of adverse events was similar between the icotrokinra (49%) and placebo (49%) arms, with no new safety signals reported.¹

"People living with moderate-to-severe plaque psoriasis are seeking options that balance efficacy, safety and ease of use," said Robert Bissonnette, M.D., Chairman at Innovaderm Research, Montreal, Canada and ICONIC-LEAD study investigator.d "These study results are promising, and show the potential for treatment with icotrokinra to offer patients the unique combination of complete skin clearance and a favorable safety profile in a once daily pill."¹

Topline results from the ICONIC-ADVANCE 1 and 2 studies also met co-primary endpoints (IGA 0/1 and PASI 90 at Week 16 vs placebo), while demonstrating superiority to deucravacitinib in key secondary endpoints at Weeks 16 and 24.²³ These findings set the stage for ICONIC-ASCEND, a global Phase 3 trial comparing once-daily oral icotrokinra to ustekinumab in moderate-to-severe plaque PsO—the first head-to-head study of an oral psoriasis therapy against a biologic.¹

"The robust results seen to date underscore the potential for icotrokinra to shift treatment expectations in moderate-to-severe plaque psoriasis," said Liza O'Dowd, Vice President, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine, in a news release. "As part of our ongoing commitment to pioneer innovations for patients, we are proud to advance this first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, which shows promise as a potential first-line systemic therapy for the treatment of plaque psoriasis."¹

The ICONIC program comprises multiple Phase 3 studies evaluating the efficacy and safety of icotrokinra in moderate-to-severe plaque PsO, including:

• ICONIC-LEAD (NCT06095115): Compared icotrokinra with placebo in 684 participants.
• ICONIC-TOTAL (NCT06095102): Evaluates icotrokinra in PsO involving special areas (e.g., scalp, genital, hands/feet).
• ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604): Compare icotrokinra to placebo and deucravacitinib.
• ICONIC-ASCEND (Phase 3, planned): First head-to-head oral vs injectable trial (icotrokinra vs ustekinumab).¹

Icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor, which is implicated in multiple inflammatory conditions including plaque psoriasis and ulcerative colitis. Developed under a license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc. (a Johnson & Johnson company), icotrokinra is undergoing Phase 3 trials for PsO and Phase 2b investigation in ulcerative colitis.

Plaque psoriasis is a chronic, immune-mediated disease that affects an estimated 8 million Americans and more than 125 million people worldwide. Characterized by overproduction of skin cells, PsO manifests as inflamed, scaly plaques that can be painful or pruritic. On darker skin, lesions may appear darker, thicker, or more purple, gray, or brown, and PsO can pose significant psychosocial burdens on patients.

Reference

1. Johnson & Johnson. Johnson & Johnson announces Phase 3 data for icotrokinra (JNJ-2113) and the start of a head-to-head superiority study in plaque psoriasis. Press release. March 8, 2025.