Johnson & Johnson's investigational oral peptide, icotrokinra (JNJ-2113), has demonstrated positive topline results in two pivotal Phase 3 trials, ICONIC-LEAD and ICONIC-TOTAL, for the treatment of moderate to severe plaque psoriasis. The drug, a first-in-class targeted oral peptide, selectively blocks the IL-23 receptor and has shown significant skin clearance in both adult and adolescent patients. These findings, announced on November 18, 2024, highlight the potential of icotrokinra as a novel oral therapy for psoriasis, addressing a significant unmet need in patients who are eligible for but not receiving advanced therapies.
Efficacy Results from ICONIC-LEAD
The ICONIC-LEAD study, a randomized controlled trial, evaluated the safety and efficacy of icotrokinra compared to placebo in participants aged 12 years and older with moderate to severe plaque psoriasis. The co-primary endpoints were PASI 90 (Psoriasis Area and Severity Index 90) and IGA (Investigator's Global Assessment) score of 0/1 at week 16. Results showed that at week 16, 64.7% of patients treated with icotrokinra achieved IGA scores of 0/1 (clear or almost clear skin), and 49.6% achieved PASI 90, compared to 8.3% and 4.4% on placebo, respectively. Furthermore, response rates continued to improve through week 24, with 74.1% of patients on icotrokinra achieving IGA scores of 0/1 and 64.9% achieving PASI 90.
ICONIC-TOTAL Study Findings
The ICONIC-TOTAL study also demonstrated positive topline results, meeting its primary endpoint of IGA 0/1 at week 16 compared to placebo. This trial focused on patients with psoriasis affecting special areas such as the scalp, genitals, and/or hands and feet. Comprehensive results from both ICONIC-LEAD and ICONIC-TOTAL are being prepared for presentation at upcoming medical congresses and will be shared with health authorities in planned submissions.
Safety and Tolerability
The safety data from the ICONIC-LEAD study were consistent with previous Phase 2 FRONTIER 1 and 2 studies. A similar proportion of patients experienced adverse events (AEs) between the icotrokinra and placebo groups, with 49.3% and 49.1% of participants experiencing a treatment-emergent adverse event (TEAE) at week 16, respectively.
Mechanism of Action and Clinical Significance
Icotrokinra is designed to selectively block the IL-23 receptor, which plays a crucial role in the inflammatory response in moderate to severe plaque psoriasis. By binding to the IL-23 receptor with high affinity, icotrokinra inhibits IL-23 signaling in human T cells, thereby reducing inflammation and improving skin clearance. Liza O'Dowd, Vice President, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine, stated, "Icotrokinra has the potential to offer once-daily oral therapy that could help address the needs and preferences of people living with plaque psoriasis."
Ongoing and Future Studies
Johnson & Johnson is continuing to investigate icotrokinra in other Phase 3 trials, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will compare the drug to both placebo and deucravacitinib. Additionally, a Phase 3 program, ICONIC-PsA, will be initiated in early 2025 to investigate icotrokinra in psoriatic arthritis.
About Plaque Psoriasis
Plaque psoriasis is a chronic immune-mediated disease affecting millions worldwide, characterized by inflamed, scaly plaques on the skin. Approximately one-quarter of patients have moderate to severe cases. The condition can significantly impact a person's physical and emotional health, relationships, and overall quality of life.
