78 A Phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for moderate-to-severe plaque psoriasis: Efficacy of overall and scalp psoriasis responses from FRONTIER 1

Introduction: JNJ-77242113 is a competitive oral peptide antagonist that binds with high affinity to the interleukin-23 receptor (IL-23R), and selectively inhibits IL-23 proximal and downstream cytokine production. Objective: To evaluate the efficacy and safety of orally administered JNJ-77242113 in moderate-to-severe plaque psoriasis. Methods: In FRONTIER-1, patients were randomized 1:1:1:1:1:1 to receive JNJ-77242113 25mg daily (QD), 50mg QD, 25mg twice daily (BID), 100mg QD, 100mg BID, or placebo (PBO) through Week (W)16. Primary endpoint was the proportion of patients achieving PASI75 at W16. PASI90, PASI100, IGA score of cleared/minimal (0/1), IGA score 0, and scalp-specific (ss)-IGA score of 0/1 with ≥2-grade improvement from baseline at W16 were also evaluated. Patients with intercurrent events (ICEs), including discontinuation of study agent due to lack of efficacy, worsening of psoriasis, or use of a prohibited psoriasis treatment, were considered non-responders at W16. Observed data were used for patients who discontinued study agent for other reasons. After accounting for ICEs, patients with missing data were considered non-responders. Results: A significant dose response was observed for the primary endpoint of PASI75 (PBO 9.3%[n=43], JNJ-77242113: 25mg QD 37.2%[n=43], 25mg BID 51.2%[n=41], 50mg QD 58.1%[n=43], 100mg QD 65.1%[n=43], 100mg BID 78.6%[n=42]). Response rates (PASI75, PASI90, PASI100, IGA score 0/1, IGA score 0), including ss-IGA score 0/1 with ≥2-grade improvement from baseline (PBO 11.4%[n=35], JNJ-77242113: 25mg QD 32.4%[n=37], 25mg BID 65.6%[n=32], 50mg QD 70.0%[n=40], 100mg QD 67.5%[n=40], 100mg BID 75.0%[n=36]), for all JNJ-77242113 doses were significantly higher than PBO (nominal p<0.05 for all comparisons) at W16. Proportions of patients with adverse events (AEs) were comparable between JNJ-77242113 groups and PBO. Most frequently reported AEs were COVID-19 and nasopharyngitis with no dose-dependent trends. Conclusion: JNJ-77242113 is a first-in-class oral IL-23R antagonist peptide that demonstrated significantly greater efficacy vs PBO in moderate-to-severe plaque psoriasis, including scalp psoriasis, and was well-tolerated in all treatment groups.