OP0234\u2005EFFICACY AND SAFETY OF BRODALUMAB, AN ANTI-INTERLEUKIN-17 RECEPTOR A MONOCLONAL ANTIBODY, IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: A 16 WEEK RESULTS OF A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Abstract

Background It is known that clinical features and pathophysiological pathways of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) have similarities. Recent reports suggest that IL-17 signaling pathway may be involved in development of axial spondyloarthritis (axSpA). Here we reported the confirmatory phase 3 trial of brodalumab, a human anti-interleukin-17 receptor A monoclonal antibody, in patients with axSpA (4827-006 Study, NCT02985983). Objectives To evaluate the efficacy and safety of brodalumab in axSpA (including AS and nr-axSpA) patients at week 16. Methods In this phase 3, multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, South Korea and Taiwan, eligible axSpA patients were randomized 1:1 to brodalumab subcutaneously (s.c.) 210 mg or placebo at baseline, weeks 1 and 2, every 2 weeks thereafter. At week 16, all subjects entered an open label extension phase and received brodalumab 210 mg s.c. Q2W. ASAS 40 (Assessment of SpondyloArthritis international Society) response rate at week 16 was the primary endpoint. Secondary outcomes and safety profiles were also assessed. Results A total of 159 patients were randomized, and 77/80 patients in brodalumab arm and 69/79 patients in placebo arm were completed the 16 weeks’ double-blind phase study. The ASAS 40 response rate at week 16 was significantly higher in brodalumab group (35/80, 43.8%, p=0.018) compared to placebo group (19/79, 24.1%). Other disease activity parameters demonstrated trend to improvement in therapeutic arm (Table). Brodalumab 210 mg had good safety profile. Most commonly reported adverse event was nasopharyngitis observed in both brodalumab (11.1%) and placebo (10.3%) arms. AE rates including SAE rates were comparable between groups. No suicidal ideation or behavior were observed. Conclusion Brodalumab s.c. 210 mg Q2W treatment was effective and tolerable in axSpA patients in this 16 week phase 3 clinical trial. Based on the ongoing trial results, brodalumab could be considered as a future therapeutic option for patients with axSpA.Table 1 Summary of efficacy result at Week 16 (FAS) Efficacy End Points axSpA (N=159) Placebo(N=79) 210 mg Brodalumab(N=80) ASAS 40 Response at Week 16 (NRI), n (%) 19 (24.1) 35 (43.8, p=0.018) ASAS 20 Response at Week 16 (NRI), n (%) 33 (41.8) 54 (67.5) ASDAS-CRP change from baseline at Week 16 (BOCF), LS mean -0.672 -1.127 BASDAI change from baseline at Week 16, Mean -2.4 -2.9 BASFI change from baseline at Week 16, Mean -0.7 -1.1 FAS, Full Analysis Set; NRI, Non responder inputation; BOCF, Baseline Observation Carried Forward; LS mean is based on ANCOVA model adjusted with the baseline, treatment group, strata of CRP level at screening (>= ULN and < ULN), region (Japan, Korea, Taiwan), and disease subpopulations (AS, nr-axSpA). Figure. ASAS 20/40 response rate Disclosure of Interests James Cheng-Chung Wei Grant/research support from: Abbvie, BMS, Celgene, Janssen, Novartis, Pfizer, and UCB pharma, Consultant for: TSH Taiwan, Speakers bureau: Janssen, Novartis, Pfizer and TSH, Tae-hwan Kim: None declared, Mitsumasa Kishimoto Consultant for: Kyowa Hakko Kirin Co., Ltd., Takuya Morishige Employee of: Kyowa Hakko Kirin Co., Ltd., Naoki Ogusu Employee of: Kyowa Hakko Kirin Co., Ltd., Shigeto Kobayashi Grant/research support from: Chugai pharmaceutical Co., Ltd., Consultant for: Kyowa Hakko Kirin Co., Ltd., Eli Lilly, Novartis.