ROZIBAFUSP ALFA IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A BAYESIAN ADAPTIVE PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY

PT014 / #285 Topic: AS24 - SLE-Treatment POSTER TOUR 03: RECENT ADVANCEMENTS IN SLE CLINICAL OUTCOMES AND THERAPY 23-05-2025 10:00 AM - 10:40 AM Background/Purpose SLE is a multisystem autoimmune disorder driven by diverse immunological mechanisms. Dysregulation of T and B cell interactions results in class-switched immunoglobulin G (IgG) autoantibodies, a hallmark of SLE. SLE disease activity is associated with elevated expression of 2 key mediators of T and B Cells: inducible costimulatory ligand (ICOSL) and B cell activating factor (BAFF). Rozibafusp alfa is a novel bispecific IgG2 antibody-peptide conjugate that targets dual inhibition of ICOSL and BAFF. This phase 2b study ( NCT04058028 ) evaluated the efficacy and safety of rozibafusp alfa in adults with active SLE. Methods This was a Bayesian adaptive phase 2b, randomized, double-blind, placebo-controlled, multicenter, dose-ranging study in adult patients with active SLE with Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score ≥ 6, clinical hSLEDAI score ≥ 4 and inadequate response to standard of care (SOC) therapies. Patients were randomized to receive placebo or rozibafusp alfa 70 mg, 280 mg or 420 mg every 2 weeks for 52 weeks (Figure). The randomization ratio started as 1:1:1:1, then was adapted using Response Adaptive Randomization to allocate more patients to more efficacious doses and fewer patients to less efficacious doses, with a fixed 25% allocation to placebo based on the clinical efficacy at prespecified interim analyses (IAs).[1] The first IA was conducted, blinded to the investigators, when the first 40 enrolled patients completed Week 24. Subsequent IAs were conducted each time 32 more patients reached Week 24. Futility analyses utilized a Bayesian hierarchical model at each IA. The primary endpoint was the achievement of SLE Responder Index 4 (SRI-4) response at Week 52, defined as a ≥ 4-point reduction from baseline in the hSLEDAI score, no new British Isles Lupus Assessment Group (BILAG) 2004 A and no > 1 new BILAG B scores, a < 0.3-point deterioration in Physician’s Global Assessment, and no increase in treatment beyond protocol-allowed therapies. Patients were followed up for a minimum of 16 weeks for safety. Figure. Clinical trial design utilizing response adaptive randomization Results The study met predefined futility criteria at the sixth IA. At the time when the trial was terminated, 244 participants (93.4% female; mean [SD] age: 43.5 [10.9] years) had been enrolled. Among these participants, 134 patients in rozibafusp alfa groups (70 mg: n = 51; 280 mg: n = 35; 420 mg: n = 48) and 43 patients in placebo had the opportunity to complete Week 52 visit. The percentage of participants with an SRI-4 response at Week 52 did not substantially differ between the rozibafusp alfa groups (56.9-72.9%) and placebo (60.5%). A total of 243 patients who received at least 1 dose of study drug were included in the safety analysis. Treatment-emergent adverse events were observed at similar frequencies between rozibafusp alfa groups (63.9-81.6%) and placebo (67.7%). Serious adverse events occurred comparably in the rozibafusp alfa groups (3.5%-13.9%) and placebo (9.7%) (Table). The discontinuation of this trial was due to prespecified futility criteria but not related to any safety concerns. Table. Safety of rozibafusp alfa In patients with active SLE Conclusions With high placebo response rates, rozibafusp alfa did not show substantial added benefit over SOC for SLE treatment. Rozibafusp alfa was safe and well tolerated in patients with active SLE. Reference: [1.] Garces S. Lupus Sci Med 2023;10:e000890.

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