BackgroundBimekizumab (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.1,2ObjectivesTo 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.MethodsBE 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.ResultsOf 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; p50% of pts initially randomised to BKZ had achieved ASDAS Table 1.Efficacy at Wks 16 and 24BLWk 16Wk 24PBO N=126BKZ 160 mg Q4W N=128PBO N=126BKZ 160 mg Q4W N=128p valuePBO→BKZ 160 mg Q4W N=126BKZ 160 mg Q4W N=128Ranked endpoints in hierarchical orderASAS40* [NRI] n (%)--27 (21.4)61 (47.7)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)–3.2 (0.2)–3.4 (0.2)ASAS20† [NRI] n (%)--48 (38.1)88 (68.8)87 (69.0)96 (75.0)ASAS PR† [NRI] n (%)--9 (7.1)33 (25.8)35 (27.8)37 (28.9)ASDAS-MI† [NRI] n (%)--9 (7.1)35 (27.3)37 (29.4)41 (32.0)ASAS 5/6† [NRI] n (%)--21 (16.7)49 (38.3)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)–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)–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)–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)10.1 (0.8)10.6 (0.8)Other endpointsdEnthesitis-free state†a [NRI] n (%)--22 (23.9)b48 (51.1)c-40 (43.5)b45 (47.9)cASAS40 in TNFi-experienced [NRI] n (%)--2 (11.8)e6 (60.0)f---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 CfBg [OC] mean (SD)1.9 (3.2)h1.6 (2.9)i–0.1 (1.7)j–0.7 (2.2)k---SPARCC MRI SIJ score CfBg [OC] mean (SD)10.5 (13.8)l8.5 (10.3)m–1.5 (9.2)n–6.3 (10.0)o---Randomised set. *Primary endpoint; †Secondary endpoint; aMASES=0 in pts with BL MASES >0; bn=92; cn=94; dNominal p values not shown; en=17; fn=10; gIn pts in MRI sub-study; hn=65; in=75; jn=58; kn=73; ln=68; mn=79; nn=60; on=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.ConclusionDual 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.1,2References[1]van der Heijde D. Ann Rheum Dis 2020;79:595–604;[2]Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491.AcknowledgementsThis study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of InterestsAtul 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