0411: Bimekizumab Improves Signs and Symptoms Including Inflammation in Patients with Active Ankylosing Spondylitis: 24-Week Efficacy & Safety from a Phase 3, Multicenter, Randomized, Placebo Controlled Study

Désirée van der Heijde¹, Xenofon Baraliakos², Maxime Dougados³, Matthew Brown⁴, Denis Poddubnyy⁵, Filip Van den bosch⁶, Nigil Haroon⁷, Huji Xu⁸, Tetsuya Tomita⁹, Lianne Gensler¹⁰, Marga Oortgiesen¹¹, Carmen Fleurinck¹², Natasha de Peyrecave¹³, Thomas Vaux¹⁴, Alexander Marten¹⁵ and Atul Deodhar¹⁶, ¹Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Leiden, Netherlands, ²Rheumazentrum Ruhrgebiet Herne, Herne, Germany, ³Department of Rheumatology, Hôpital Cochin, Paris, France, Paris, France, ⁴Genomics England, London, United Kingdom, ⁵Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁶Department of Internal Medicine and Paediatrics, Ghent University and VIB Centre for Inflammation Research, Ghent, Belgium, ⁷Schroeder Arthritis Institute, University Health Network; University of Toronto, Toronto, ON, Canada, ⁸Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Affiliated to Second Military Medical University, Shanghai, China, ⁹Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Osaka, Japan, Suita Osaka, Japan, ¹⁰Department of Medicine, Division of Rheumatology, University of California San Francisco, San Francisco, CA, ¹¹UCB Pharma, Raleigh, NC, ¹²UCB Pharma, Brussels, Belgium, Oosterzele, Belgium, ¹³UCB Pharma, Brussels, Belgium, ¹⁴UCB Pharma, Slough, United Kingdom, ¹⁵UCB Pharma, Monheim am Rhein, Germany, ¹⁶Oregon Health & Science University, Portland, OR, USA, Portland, OR

Background/Purpose: Bimekizumab (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).^1,2 Here, we 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.

Methods: BE MOBILE 2 (NCT03928743) comprises a 16-wk double blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 years (yrs), met modified New York Criteria and had active AS (BASDAI ≥4, spinal pain ≥4) at baseline (BL). Pts were randomized 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, and up to Wk 24. Treatment-emergent adverse events (TEAEs; MedDRA v19.0) are reported among patients who received ≥1 BKZ dose by preferred term up to Wk 24.

Results: Of 332 randomized 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; 27.7% pts female, 85.5% HLA-B27+, 16.3% TNFi-inadequate responders (IR).

At Wk 16, the primary (ASAS40: 44.8% BKZ vs 22.5% PBO; p< 0.001) and all ranked secondary endpoints were met (Table). ASAS40 responses at Wk 16 were consistent across both TNFi-naïve (45.7% BKZ vs 23.4% PBO) and TNFi-IR (40.5% BKZ vs 17.6% PBO) populations. Responses with BKZ were rapid, including in PBO pts who switched to BKZ at Wk 16, and increased to Wk 24 (Table; Figure 1). At Wk 24, nearly 50% BKZ-randomized pts had achieved ASDAS < 2.1 (Figure 1).

Substantial reductions from BL in SPARCC MRI SIJ inflammation and Berlin MRI Spine scores by Wk 16, and hs-CRP by Wk 2, were achieved with BKZ vs PBO (Figure 2). A higher proportion of pts with SPARCC MRI SIJ and Berlin MRI Spine scores >2 at BL achieved MRI remission (score ≤2) at Wk 16 with BKZ vs PBO. Among CRP+ pts (hs-CRP >5.0 mg/L), a greater proportion of pts treated with BKZ vs PBO achieved normalization (hs-CRP ≤5.0 mg/L) of CRP through Wk 16. For pts who switched from PBO to BKZ at Wk 16, Wk 24 normalization rates approached those seen in BKZ-randomized pts (Figure 2).

At Wk 24, 183/330 (55.5%) pts had ≥1 TEAE on BKZ; most frequent were nasopharyngitis (6.4%), diarrhea (3.9%), headache (3.6%) and oral candidiasis (3.0%). All fungal infections were non-severe and non-systemic; 2 (0.6%) led to treatment discontinuation. Up to Wk 24, incidence of serious TEAEs was low (3.6%); no active tuberculosis, MACE or deaths were reported; incidence of adjudicated IBD (0.3%) and uveitis (0.6%) were low.

Conclusion: Dual 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, including suppression of inflammation. No new safety signals were observed.^1,2

References: 1. van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491.





Disclosures: D. van der Heijde, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Novartis, Pfizer, UCB, Imaging Rheumatology bv, Lilly; X. Baraliakos, AbbVie, Lilly, Galapagos, MSD, Novartis, Pfizer, UCB, Bristol-Myers Squibb, Janssen, Roche, Sandoz, Sanofi; M. Dougados, Novartis, AbbVie, Eli Lilly, Merck, Pfizer, UCB Pharma; M. Brown, UCB Pharma, Pfizer, Clementia, Ipsen, Incyte, Regeneron, Grey Wolf Therapeutics, Xinthera, Novartis; D. Poddubnyy, AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, MSD, Moonlake, Novartis, Pfizer, Samsung-Bioepis, UCB; F. Van den bosch, AbbVie, Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, UCB, Amgen, Bristol-Myers Squibb(BMS), Celgene; N. Haroon, AbbVie/Abbott, Janssen, Eli Lilly, Novartis, UCB; H. Xu, None; T. Tomita, Graduate School of Health Sciences, Morinomiya University of Medical Sciences, Osaka, Japan, AbbVie, Eli Lilly, Gilead, Novartis, Pfizer, Astellas, Bristol-Myers Squibb (BMS), Eisai, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Osaka, Japan; L. Gensler, Novartis, Pfizer Inc, UCB Pharma, AbbVie, Eli Lilly, Janssen, Gilead, Moonlake; M. Oortgiesen, UCB Pharma; C. Fleurinck, UCB Pharma; N. de Peyrecave, UCB Pharma, GlaxoSmithKlein (GSK); T. Vaux, UCB Pharma; A. Marten, UCB Pharma; A. Deodhar, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake.