P41 Phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER-2

Abstract JNJ-77242113, a targeted oral peptide, inhibits interleukin (IL)-23 signalling by binding the IL-23 receptor. At all doses, JNJ-77242113 showed superior efficacy at Week (W)16 vs. placebo in moderate-to-severe psoriasis in FRONTIER-1. FRONTIER-2 was a multicentre, long-term extension, double-blind, dose-ranging, Phase 2b study evaluating efficacy and safety of JNJ-77242113 in adults with moderate-to-severe plaque psoriasis who were candidates for systemic treatment or phototherapy. FRONTIER-1 randomized patients 1:1:1:1:1:1 to JNJ-77242113 25 mg daily (QD), 25 mg twice daily (BID), 50 mg QD, 100 mg QD, 100 mg BID, or placebo through W16. In FRONTIER-2, patients completing FRONTIER-1 (at W16) continued their assigned dose through W52; those randomized to placebo crossed over to 100 mg QD (PBO→100 mg QD). The primary endpoint was the proportion of patients achieving ≥75% improvement in psoriasis area and severity index (PASI75) at W52. Response rates were estimated using non-responder imputation and FRONTIER-1 baseline data. Response rates among JNJ-77242113–treated patients from FRONTIER-1 were maintained, across dose groups, through W52. Patients who crossed over to JNJ-77242113 from placebo at W16 (PBO→100 mg QD) had substantially higher response rates at W52. At W52, proportions of patients achieving PASI75 with JNJ-77242113 were: 25 mg QD 48.8%, 25 mg BID 58.5%, 50 mg QD 69.8%, 100 mg QD 65.1%, 100 mg BID 76.2%; PBO→100 mg QD 65.7%; the respective PASI90/PASI100 rates were 27.9%/14.0%, 36.6%/17.1%, 41.9%/20.9%, 51.2%/25.6%, 64.3%/40.5%, 57.1%/34.3%. Proportions of patients achieving an Investigator’s Global Assessment (IGA) score of 0/1 or 0 with JNJ-77242113 at Week 52 were: 25 mg QD 37.2%/14.0%, 25 mg BID 46.3%/19.5%, 50 mg QD 60.5%/23.3%, 100 mg QD 60.5%/30.2%, 100 mg BID 73.8%/42.9%, and PBO→100 mg QD 65.7%/31.4%. Approximately 90% of patients receiving JNJ-77242113 100 mg BID who had achieved a PASI75, PASI90, or IGA 0/1 response at W16 maintained the response at W52. Across dose groups, 58.6% of patients experienced adverse events (AEs), with no evidence of a dose-dependent increase in AEs, including gastrointestinal disorders. The proportion of patients with serious AEs through W52 was 4%; all serious AEs were considered unrelated to study treatment. In patients with psoriasis receiving JNJ-77242113, the first targeted oral peptide to selectively block IL-23 pathway signalling, rates of near-complete/complete skin clearance from FRONTIER-1 were maintained through W52; the highest response rates were seen in patients randomized to JNJ-77242113 100 mg BID. Among patients who had achieved a PASI or IGA response at W16, responses were maintained in substantial proportions of patients at W52. Consistent with prior studies, no safety signals were identified.