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

Background: More patients with moderate-to-severe plaque psoriasis achieved responses with JNJ-77242113, a targeted oral peptide inhibiting interleukin-23 receptor signaling, versus placebo (PBO) at week (W)16 of the phase 2 FRONTIER-1 study. Objective: FRONTIER-2, a long-term extension of FRONTIER-1, evaluated JNJ-77242113 through 1 year. Methods: FRONTIER-1 participants received JNJ-77242113 at doses from 25 mg daily to 100 mg twice daily or PBO through W16. Patients completing FRONTIER-1 could enroll in FRONTIER-2 and continue JNJ-77242113 at the same dose through W52. Those on PBO crossed over to JNJ-77242113 100 mg daily for W16–52. Safety follow-up continued through W56. Results: Most (89%) FRONTIER-1 patients continued to FRONTIER-2. Across outcomes, response rates were maintained from W16–52. The highest response rates generally occurred with JNJ-77242113 100 mg twice daily. At W52, 76% of patients achieved up to 75% improvement in Psoriasis Area and Severity Index (PASI75) with 100 mg twice daily; rates of clear or almost clear skin were 64% (PASI90), 74% (Investigator's Global Assessment 0/1), 40% (PASI100), and 43% (Investigator's Global Assessment 0). From W16–56, 59% of JNJ-77242113–treated patients had ≥1 adverse events. Serious adverse events, considered unrelated to treatment by investigators, occurred in 4% of patients. Limitations: The study was limited by the small number of patients in each treatment group and the descriptive nature of the longer-term data. Conclusion: Rates of skin clearance with JNJ-77242113 were durable to 1 year and no safety signals were identified.