OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY

Abstract

BackgroundBimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. In a phase 2b study, BKZ showed rapid and sustained efficacy and was well tolerated up to 156 weeks (wks) in patients (pts) with active ankylosing spondylitis (AS).1,2ObjectivesTo assess efficacy and safety of BKZ vs placebo (PBO) in pts with active AS up to Wk 24 in the ongoing pivotal phase 3 study, BE MOBILE 2.MethodsBE MOBILE 2 (NCT03928743) comprises a 16-wk double-blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 yrs, met modified New York criteria and had active AS (BASDAI ≥4, spinal pain ≥4) at BL. Pts were randomised 2:1, 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 332 randomised pts (BKZ: 221; PBO: 111), 322 (97.0%) completed Wk 16 and 313 (94.3%) Wk 24. BL characteristics were comparable between groups: mean age 40.4 yrs, symptom duration 13.5 yrs; 72.3% pts male, 85.5% HLA-B27+, 16.3% TNFi-experienced. At Wk 16, the primary (ASAS40: 44.8% BKZ vs 22.5% PBO; p<0.001) and all ranked secondary endpoints were met (Table 1). Responses with BKZ were rapid, 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 and spine inflammation by Wk 16 were achieved with BKZ vs PBO (Table 1). At Wk 24, ≥50% pts had achieved ASDAS <2.1 (Figure 1).Table 1.Efficacy at Wks 16 and 24BLWk 16Wk 24PBO N=111BKZ 160 mg Q4W N=221PBO N=111BKZ 160 mg Q4W N=221p valuePBO→BKZ 160 mg Q4W N=111BKZ 160 mg Q4W N=221Ranked endpoints in hierarchical orderASAS40* [NRI] n (%)--25 (22.5)99 (44.8)<0.00163 (56.8)119 (53.8)ASAS40 in TNFi-naïve† [NRI] n (%)--22 (23.4)a84 (45.7)b<0.00156 (59.6)a100 (54.3)bASAS20† [NRI]n (%)--48 (43.2)146 (66.1)<0.00185 (76.6)159 (71.9)BASDAI CfB† [MI] mean (SE)6.5 (0.1)6.5 (0.1)–1.9 (0.2)–2.9 (0.1)<0.001–3.3 (0.2)–3.3 (0.1)ASAS PR† [NRI]n (%)--8 (7.2)53 (24.0)<0.00128 (25.2)56 (25.3)ASDAS-MI† [NRI] n (%)--6 (5.4)57 (25.8)<0.00143 (38.7)67 (30.3)ASAS 5/6† [NRI]n (%)--16 (14.4)94 (42.5)<0.00157 (51.4)107 (48.4)BASFI CfB† [MI] mean (SE)5.2 (0.2)5.3 (0.2)–1.1 (0.2)–2.2 (0.1)<0.001–2.2 (0.2)–2.4 (0.2)Nocturnal spinal pain CfB† [MI]mean (SE)6.8 (0.2)6.6 (0.1)–1.9 (0.2)–3.3 (0.2)<0.001–3.7 (0.3)–3.8 (0.2)ASQoL CfB† [MI] mean (SE)8.5 (0.4)9.0 (0.3)–3.2 (0.3)–4.9 (0.3)<0.001–4.9 (0.4)–5.4 (0.3)SF-36 PCS CfB† [MI] mean (SE)34.6 (0.8)34.4 (0.6)5.9 (0.8)9.3 (0.6)<0.00110.6 (0.8)10.8 (0.6)BASMI CfB† [MI] mean (SE)3.8 (0.2)3.9 (0.1)–0.2 (0.1)–0.5 (0.1)0.005–0.5 (0.1)–0.6 (0.1)Other endpointsnEnthesitis-free state†c [NRI]n (%)--22 (32.8)d68 (51.5)e-33 (49.3)d70 (53.0)eASAS40 in TNFi-experienced [NRI]n (%)--3 (17.6)f15 (40.5)g---ASDAS-CRP CfB [MI]mean (SE)3.7 (0.1)3.7 (0.1)–0.7 (0.1)–1.4 (0.1)-–1.7 (0.1)–1.6 (0.1)hs-CRP (mg/L) [MI] geometric mean (median)6.7 (6.3)6.5 (8.2)6.0 (6.3)2.4 (2.4)-1.9 (2.2)2.1 (2.3)MRI spine Berlin CfBh [OC] mean (SD)3.3 (4.9)i3.8 (5.3)j0.0 (1.4)k–2.3 (3.9)l---SPARCC MRI SIJ score CfBh [OC] mean (SD)5.8 (7.7)i7.4 (10.7)m1.1 (6.9)k–5.6 (9.9)l---Randomised set. *Primary endpoint; †Secondary endpoint; an=94; bn=184; cMASES=0 in pts with BL MASES >0; dn=67; en=132; fn=17; gn=37; hIn pts in MRI sub-study; in=45; jn=82; kn=43; ln=79; mn=83; nNominal p values not shown.Over 16 wks, 120/221 (54.3%) BKZ pts had ≥1 TEAE vs 48/111 (43.2%) PBO; three most frequent on BKZ were nasopharyngitis (BKZ: 7.7%; PBO: 3.6%), headache (4.1%; 4.5%) and oral candidiasis (4.1%; 0%). No systemic candidiasis was observed. Up to 16 wks, incidence of SAEs was low (1.8%; 0.9%); no MACE or deaths were reported; 2 (0.9%) IBD cases occurred in pts on BKZ.ConclusionDual inhibition of IL-17A and IL-17F with BKZ in pts with active AS 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 InterestsDésirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Employee of: Imaging Rheumatology BV (Director), 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, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Merck, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Matt Brown Speakers bureau: Novartis, Consultant of: Pfizer, Clementia, Ipsen, Regeneron, Grey Wolf Therapeutics, Grant/research support from: UCB Pharma, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Filip van den Bosch Speakers bureau: AbbVie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Nigil Haroon Consultant of: AbbVie, Amgen, Janssen, Merck, Novartis and UCB Pharma, Huji Xu: None declared, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis, and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis, and Pfizer, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis, Pfizer, and UCB Pharma; paid to institution, Marga Oortgiesen Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, 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.