BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO‑CONTROLLED STUDY

Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. BKZ has shown rapid and sustained efficacy and was well tolerated up to 156 weeks (wks) in a phase 2b study in patients (pts) with active ankylosing spondylitis. Objectives: To assess efficacy and safety of BKZ vs placebo (PBO) in pts with active non-radiographic axial spondyloarthritis (nr-axSpA) up to Wk 24 in the ongoing pivotal phase 3 study, BE MOBILE 1. Methods: BE MOBILE 1 (NCT03928704) comprises a 16-wk double-blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 yrs, had BASDAI ≥4 and spinal pain ≥4 at BL, and sacroiliitis on MRI and/or elevated CRP at screening. Pts were randomised 1:1, BKZ 160 mg Q4W:PBO. From Wk 16, all pts received BKZ 160 mg Q4W. Primary and secondary efficacy endpoints were assessed at Wk 16. Results: Of 254 randomised pts (BKZ: 128; PBO: 126), 244 (96.1%) completed Wk 16, 240 (94.5%) Wk 24. BL characteristics were comparable between groups: mean age 39.4 yrs, symptom duration 9.0 yrs; 54.3% pts male, 77.6% HLA-B27+, 10.6% TNFi-experienced. At Wk 16, the primary (ASAS40: 47.7% BKZ vs 21.4% PBO; p<0.001) and all ranked secondary endpoints were met ( Table 1 ). Responses were rapid with BKZ, including in PBO pts who switched to BKZ at Wk 16, and increased to Wk 24 ( Figure 1 ; Table 1 ). Substantial reductions of hs-CRP by Wk 2 and MRI SIJ inflammation by Wk 16 were achieved with BKZ vs PBO ( Table 1 ). At Wk 24, >50% of pts initially randomised to BKZ had achieved ASDAS <2.1 ( Figure 1 ). Table 1. Efficacy at Wks 16 and 24 BL Wk 16 Wk 24 PBO N=126 BKZ 160 mg Q4W N=128 PBO N=126 BKZ 160 mg Q4W N=128 p value PBO→BKZ 160 mg Q4W N=126 BKZ 160 mg Q4W N=128 Ranked endpoints in hierarchical order ASAS40 * [NRI] n (%) - - 27 (21.4) 61 (47.7) <0.001 59 (46.8) 67 (52.3) BASDAI CfB [MI] mean (SE) 6.7 (0.1) 6.9 (0.1) –1.5 (0.2) –3.1 (0.2) <0.001 –3.2 (0.2) –3.4 (0.2) ASAS20 [NRI] n (%) - - 48 (38.1) 88 (68.8) <0.001 87 (69.0) 96 (75.0) ASAS PR [NRI] n (%) - - 9 (7.1) 33 (25.8) <0.001 35 (27.8) 37 (28.9) ASDAS-MI [NRI] n (%) - - 9 (7.1) 35 (27.3) <0.001 37 (29.4) 41 (32.0) ASAS 5/6 [NRI] n (%) - - 21 (16.7) 49 (38.3) <0.001 51 (40.5) 57 (44.5) BASFI CfB [MI] mean (SE) 5.3 (0.2) 5.5 (0.2) –1.0 (0.2) –2.5 (0.2) <0.001 –2.3 (0.2) –2.8 (0.2) Nocturnal spinal pain CfB [MI] mean (SE) 6.7 (0.2) 6.9 (0.2) –1.7 (0.2) –3.6 (0.3) <0.001 –3.5 (0.2) –4.0 (0.3) ASQoL CfB [MI] mean (SE) 9.4 (0.4) 9.5 (0.4) –2.5 (0.4) –5.2 (0.4) <0.001 –4.8 (0.4) –5.7 (0.4) SF-36 PCS CfB [MI] mean (SE) 33.6 (0.8) 33.3 (0.7) 5.5 (0.7) 9.5 (0.7) <0.001 10.1 (0.8) 10.6 (0.8) Other endpoints Enthesitis-free state [NRI] n (%) - - 22 (23.9) 48 (51.1) - 40 (43.5) 45 (47.9) ASAS40 in TNFi-experienced [NRI] n (%) - - 2 (11.8) 6 (60.0) - - - ASDAS-CRP CfB [MI] mean (SE) 3.7 (0.1) 3.8 (0.1) –0.6 (0.1) –1.5 (0.1) - –1.5 (0.1) –1.6 (0.1) hs-CRP, mg/L [MI] geometric mean (median) 5.0 (6.5) 4.6 (6.1) 3.8 (4.1) 2.0 (1.8) - 2.3 (2.6) 1.9 (1.8) MRI spine Berlin CfB [OC] mean (SD) 1.9 (3.2) 1.6 (2.9) –0.1 (1.7) –0.7 (2.2) - - - SPARCC MRI SIJ score CfB [OC] mean (SD) 10.5 (13.8) 8.5 (10.3) –1.5 (9.2) –6.3 (10.0) - - - Randomised set. *Primary endpoint; Secondary endpoint; MASES=0 in pts with BL MASES >0; n=92; n=94; Nominal p values not shown; n=17; n=10; In pts in MRI sub-study; n=65; n=75; n=58; n=73; n=68; n=79; n=60; n=77. Over 16 wks, 80/128 (62.5%) pts had ≥1 TEAE on BKZ vs 71/126 (56.3%) on PBO; most frequent were nasopharyngitis (BKZ: 9.4%; PBO: 4.8%), upper respiratory tract infection (BKZ: 7.0%; PBO: 7.1%) and oral candidiasis (BKZ: 3.1%; PBO: 0%). No systemic candidiasis was observed. Up to 16 wks, incidence of SAEs was low (BKZ: 0.0%; PBO: 0.8%); no MACE or deaths were reported; 0 IBD cases occurred in pts on BKZ vs 1 (0.8%) in a pt on PBO. Conclusion: Dual inhibition of IL-17A and IL-17F with BKZ in pts with active nr-axSpA resulted in rapid, clinically relevant improvements in efficacy outcomes vs PBO. No new safety signals were observed. REFERENCES: [ 1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; [2]Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491. Acknowledgements: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interests: Atul Deodhar Speakers bureau: Janssen, Novartis, and Pfizer, Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Employee of: Imaging Rheumatology BV (Director), Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis, Pfizer and UCB Pharma, Huji Xu: None declared, Karl Gaffney Speakers bureau: AbbVie, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Eli Lilly, Novartis, and UCB Pharma, Grant/research support from: AbbVie, Gilead, Eli Lilly, Novartis, and UCB Pharma, Hiroaki Dobashi Speakers bureau: BMS, Chugai, Eli Lilly, GSK, MSD, Novartis, Pfizer, UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Janssen, Novartis and Pfizer, Employee of: Chief Medical Officer for CARE Arthritis, Martin Rudwaleit Speakers bureau: AbbVie, BMS, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Paid instructor for: Janssen, Novartis, and UCB Pharma, Consultant of: AbbVie, Novartis, and UCB Pharma, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and UCB Pharma, Dirk Elewaut Speakers bureau: AbbVie, Eli Lilly, Galapagos, Novartis and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Galapagos, Novartis and UCB Pharma, Marga Oortgiesen Employee of: Employee of UCB Pharma, Carmen Fleurinck Employee of: Employee of UCB Pharma, Alicia Ellis Employee of: Employee of UCB Pharma, Thomas Vaux Employee of: Employee of UCB Pharma, julie smith Employee of: Employee of UCB Pharma, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma Citation: , volume 81, supplement 1, year 2022, page 772Session: Spondyloarthritis - treatment (POSTERS only)