Johnson & Johnson has submitted a new drug application for icotrokinra, a first-in-class oral interleukin-23 (IL-23) receptor antagonist developed for moderate-to-severe plaque psoriasis.
The filing includes results from four pivotal Phase 3 trials, which showed that the once-daily peptide met all primary and key secondary endpoints, including superiority over the oral tyrosine kinase 2 (TYK2) inhibitor deucravacitinib.
Icotrokinra isn’t just another IL-23-targeting therapy. It’s the first oral peptide in the class, designed to combine biologic-like precision with the ease of oral dosing, something psoriasis researchers and developers have long aimed to achieve. While the company already markets the injectable IL-23 inhibitor TREMFYA (guselkumab), icotrokinra represents a strategic step forward in systemic treatment options.
“To date, all approved treatments targeting IL-23 are injectable,” Liza O’Dowd, Vice President of Immunodermatology and Respiratory Disease at Johnson & Johnson Innovative Medicine told DDN. “A targeted oral peptide represents a novel approach, combining the convenience of oral administration with the precision of targeted therapies.”
The drug’s design reflects a broader push to expand access to systemic care. Oral peptide drugs, engineered to survive digestion and reach circulation, aim to address both patient preference and pharmacological precision. Unlike traditional small molecules, icotrokinra binds the IL-23 receptor with high specificity, potentially reducing off-target effects.
In the ICONIC-ADVANCE 1 and 2 studies, icotrokinra not only met co-primary endpoints (Psoriasis Area and Severity Index response of 90 percent or greater improvement and an Investigator’s Global Assessment score of clear or almost clear skin) but also showed statistically significant improvements over deucravacitinib at weeks 16 and 24. The company has now launched ICONIC-ASCEND, the first head-to-head trial comparing an oral psoriasis therapy to an injectable biologic, ustekinumab.
“We designed the ICONIC program to evaluate differentiation against both oral and injectable standards of care,” O’Dowd said. “It’s part of understanding how this could work as a first-line systemic option.”
Data presented at recent medical meetings also suggest potential benefits in harder-to-treat sites like the scalp and genitals, as well as in adolescents. Long-term data and durability of response analyses are underway.
Beyond psoriasis, the drugmaker is also testing icotrokinra in ulcerative colitis and psoriatic arthritis. In the Phase 2b ANTHEM-UC study, the therapy met its primary endpoint across all dose groups and showed improvements in clinical and endoscopic outcomes at Week 12, with response rates continuing to rise through Week 28. Those results are expected to be presented later this year.
“An overabundance of IL-23 can drive chronic inflammation across the skin, joints, and gut,” O’Dowd noted. “That’s why we’re also developing icotrokinra in inflammatory bowel disease and psoriatic arthritis.”
According to GlobalData, the psoriasis market was valued at $24.5 billion in 2023 and is expected to reach nearly $40 billion by 2030, with IL-23 inhibitors projected to hold a growing share due to their favorable benefit-risk profiles.
If approved, icotrokinra could mark a shift in how IL-23-targeted therapies are delivered, offering biologic-level efficacy without an injection. For drug developers, the program also serves as a case study in how peptide engineering and head-to-head trial design can work together to push the field forward.
