Protagonist Therapeutics, in collaboration with Johnson & Johnson, has announced positive topline results from its phase 3 clinical trials, ICONIC-LEAD and ICONIC-TOTAL, evaluating JNJ-2113 (icotrokinra, formerly PN-235), a novel, oral peptide targeting the IL-23 receptor for the treatment of moderate to severe plaque psoriasis (PsO) in patients aged 12 years and older. The promising results suggest that JNJ-2113 may offer an innovative therapy for this chronic inflammatory skin condition.
Efficacy of JNJ-2113 in Plaque Psoriasis
The ICONIC-LEAD trial demonstrated substantial skin clearance compared to placebo with once-daily JNJ-2113. At week 16, 64.7% of patients treated with JNJ-2113 achieved an Investigator Global Assessment (IGA) score of 0/1, indicating clear or almost clear skin, compared to just 8.3% in the placebo group. Furthermore, 49.6% of JNJ-2113-treated patients achieved a Psoriasis Area and Severity Index (PASI 90), a significant reduction in skin lesions, versus only 4.4% of those on placebo. These results were sustained and improved at week 24, with 74.1% achieving IGA scores of 0/1 and 64.9% reaching PASI 90.
The ICONIC-TOTAL study similarly showed that JNJ-2113 met the primary endpoint of achieving IGA scores of 0/1 at week 16. The results across both studies demonstrate JNJ-2113’s potential as an effective treatment option for PsO, with skin clearance outcomes that significantly outperformed placebo.
Safety and Tolerability
Safety data from both phase 3 studies were consistent with previous phase 2b FRONTIER studies. The incidence of treatment-emergent adverse events (TEAEs) was similar between the JNJ-2113 and placebo groups. At week 16, 49.3% of JNJ-2113-treated patients and 49.1% of placebo patients experienced a TEAE, suggesting that JNJ-2113 was well tolerated. This favorable safety profile enhances its potential as a long-term treatment option for patients with moderate to severe PsO.
Future Prospects
Protagonist noted that JNJ-2113 is also being evaluated in other clinical indications. The phase 2b ANTHEM study for ulcerative colitis is expected to report topline results in early 2025. Additionally, the phase 3 ICONIC-ADVANCE studies compare JNJ-2113 against placebo and deucravacitinib in moderate to severe PsO, with results anticipated in the first half of 2025. A new phase 3 program in psoriatic arthritis will begin in 2025, expanding the therapeutic potential of JNJ-2113.
Dinesh V. Patel, PhD, president and CEO of Protagonist, stated, "We're very pleased with the ICONIC-LEAD and ICONIC-TOTAL phase 3 results, and the decision of our partner to initiate a Phase 3 program for icotrokinra in psoriatic arthritis. Our enthusiasm for icotrokinra is high heading into 2025, with phase 2b ulcerative colitis results, presentation of ICONIC Phase 3 results at medical conferences, topline results from psoriasis superiority studies against deucravacitinib and a potential psoriasis NDA submission."
With its compelling efficacy data and favorable safety profile, JNJ-2113 could significantly alter the treatment landscape for PsO and other inflammatory diseases.
