Johnson & Johnson announced publication in the New England Journal of Medicine (NEJM) of the Phase 2b FRONTIER 1 trial results for JNJ-2113. JNJ-2113 is the first and only investigational targeted oral peptide inhibitor designed to block the IL-23 receptor. IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque psoriasis (PsO) and underpins the inflammatory response in PsO and other dermatological and gastroenterological IL-23-mediated diseases. The FRONTIER 1 clinical trial achieved the primary and all secondary efficacy endpoints evaluating JNJ-2113 in adults with moderate-to-severe plaque PsO.

The primary endpoint of the study was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index score (PASI 75 response) at Week 16. Study results demonstrated a significant dose-response on PASI 75 at Week 16 for adult patients who received JNJ-2113 compared to patients treated with placebo, with 79% of patients achieving a PASI 75 response in the higher dose group tested of 100 mg twice-daily. The data were consistent with the secondary endpoints, with patients who received the higher dose of JNJ-2113 achieving PASI 100 of 40.5% and IGA 0 (clear skin) of 45.2%. Improvements were also consistent across Patient Reported Outcomes through Week 16.

Patients who were treated with JNJ-2113 demonstrated greater improvements from baseline in the severity of their disease-related symptoms by Week 16, as assessed by the Psoriasis Symptoms and Signs Diary (PSSD)c. Among patients with baseline Dermatology Life Quality Index (DLQI)e scores greater than 1, significantly higher proportions of JNJ-2113-treated patients compared with placebo-treated patients achieved DLQI scores of 0/1 (no impact on quality of life) at Week 16. In this phase 2 study, rates of adverse events (AEs) were generally similar between the JNJ-2113 and placebo groups. The most common (=5% of any treatment group) AEs were COVID-19 infection, nasopharyngitis, upper respiratory tract infection, diarrhea, headache, and cough.

No relationship between the JNJ-2113 dose group and the occurrence of AEs or serious AEs was observed. Treatment with JNJ-2113 was also associated with lower serum levels of human beta-defensin 2 (hBD-2), relative to placebo, as early as Week 4. The lowest hBD-2 level was observed with the 100 mg twice-daily dose, beginning by Week 8. Lower levels of hBD-2 were observed with clinical response and indicate inhibition of the IL-17/IL-23 axis. The pivotal Phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients with moderate-to-severe plaque PsO was initiated with two studies in Fourth Quarter 2023 ?

ICONIC-LEAD and ICONIC-TOTAL ? pursuant to the license and collaboration agreement between Protagonist Therapeutics Inc. and Janssen Biotech Inc. ICONIC-LEAD is a randomized controlled trial (RCT) to evaluate the safety and efficacy of JNJ-2113 compared with placebo in participants with moderate-to-severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-TOTAL is a RCT to evaluate the efficacy and safety of JNJ-2113 compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or palms of the hands and the soles of the feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.

Other Phase 3 studies in the development program are expected to begin in first quarter 2024, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib. The findings from the FRONTIER 1 clinical trial suggest the potential of JNJ-2113 across the spectrum of additional IL-23-mediated diseases. The Company has initiated the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis.