POS0226 BIMEKIZUMAB LONG-TERM SAFETY AND EFFICACY IN PATIENTS WITH ANKYLOSING SPONDYLITIS: 3-YEAR RESULTS FROM A PHASE 2B STUDY

Abstract

Background:Bimekizumab (BKZ), a monoclonal antibody that selectively inhibits interleukin (IL)-17A and IL-17F, has demonstrated clinical efficacy and safety in patients with ankylosing spondylitis (AS) treated over a period up to 96 weeks.1,2Objectives:To report 3-year interim safety and efficacy of BKZ in patients with active AS from a phase 2b dose-ranging study (BE AGILE; NCT02963506) and its ongoing open-label extension (OLE; NCT03355573).Methods:BE AGILE study design has been described previously.1 Patients treated with BKZ 160 mg or 320 mg every 4 weeks (Q4W) at Week 48 in BE AGILE were eligible for OLE entry. All OLE patients received BKZ 160 mg Q4W. Treatment-emergent adverse events (TEAEs) are reported for the BE AGILE safety set (patients who received ≥1 dose of BKZ on study entry) for total exposure to BKZ across BE AGILE and the OLE. Efficacy outcomes are reported for the OLE full analysis set (patients who entered the OLE and had ≥1 dose of BKZ and ≥1 valid efficacy variable measurement in the OLE), and include: ASAS40, ASAS20, ASAS PR, ASDAS, ASDAS-CII, ASDAS-MI, ASDAS-ID (<1.3) and ASDAS <2.1. Data are reported as imputed (multiple imputation [MI] based on the missing at random assumption, or non-responder imputation [NRI]) and as observed case (OC).Results:262/303 (86%) patients randomised at BE AGILE study baseline completed Week 48 on BKZ 160 mg or 320 mg. At Week 48, 255/262 (97%) patients entered the OLE (full analysis set: 254); 219 patients had an efficacy assessment at Week 156. Over the 156 weeks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) of TEAEs was 143.5, with an EAIR of 5.8 for serious TEAEs, 1.3 for serious infections, and 3.8 for Candida infections (Table 1). All Candida infections were mild or moderate; none were systemic or led to study discontinuation. Over 156 weeks, the EAIR of inflammatory bowel disease (1.2), anterior uveitis (0.8), and injection site reactions (0.5) remained low. Efficacy demonstrated at Week 48 in BE AGILE was maintained or improved up to Week 156 (Figure 1). Mean ASDAS improved from 3.9 at BE AGILE baseline to 2.0 and 1.8 at Weeks 48 and 156 respectively (by MI). At Week 156 in the NRI analyses, ASAS40 and ASAS PR were achieved by 62.6% (OC: 72.6%) and 32.7% (OC: 37.9%) patients respectively. ASDAS-ID and ASDAS <2.1 responder rates (NRI) were maintained or continued to increase from Week 48, and by Week 156, responses were achieved by 28.0% (OC: 33.0%) and 57.1% (OC: 67.4%) patients respectively. ASDAS-MI responder rates (NRI) continued to increase from 44.9% at Week 48 to 46.5% at Week 156 (OC: 52.9%).Table 1.Safety for total exposure to BKZ across BE AGILE and the OLEBE AGILEWeeks 0–48BE AGILE + OLEWeeks 0–156n (%) [EAIR/100 PY]BKZ 160 mg(n=149;114.2 PY)BKZ 320 mg(n=150;119.6 PY)All BKZ(N=303;261.3 PY)All BKZ(N=303;781.0 PY)Any TEAE103 (69.1) [168.7]122 (81.3) [221.1]235 (77.6) [186.2]280 (92.4) [143.5]Serious TEAEs5 (3.4) [4.4]6 (4.0) [5.1]13 (4.3) [5.1]43 (14.2) [5.8]Key TEAEs of special monitoringSerious infections3 (2.0) [2.7]1 (0.7) [0.8]4 (1.3) [1.5]10 (3.3) [1.3]Candida infections10 (6.7) [9.1]9 (6.0) [7.9]19 (6.3) [7.5]28 (9.2) [3.8]Inflammatory bowel disease1 (0.7) [0.9]2 (1.3) [1.7]4 (1.3) [1.5]9 (3.0) [1.2]Anterior uveitis1 (0.7) [0.9]1 (0.7) [0.8]2 (0.7) [0.8]6 (2.0) [0.8]Study discontinuations due to TEAEs7 (4.7)10 (6.7)20 (6.6)38 (12.5)Drug-related TEAEs48 (32.2)54 (36.0)110 (36.3)149 (49.2)Deaths1 (0.7)01 (0.3)2 (0.7)TEAEs are reported for the BE AGILE safety set for total exposure to BKZ across BE AGILE and the OLE. There was one death in BE AGILE (cardiac arrest) and one in the OLE (road traffic accident); neither was considered treatment-related.Conclusion:The safety profile of BKZ in patients with AS was in line with previous observations.1.2 Patients treated with BKZ demonstrated sustained and consistent efficacy over 156 weeks.