Conclusions Superior PASI 90 and IGA 0/1 responses were observed with bimekizumab compared with ustekinumab at Week 16. After one dose, faster onset of response was observed with bimekizumab compared with ustekinumab. Clinical responses with bimekizumab were durable through Week 52. Bimekizumab was well-tolerated and the safety profile was consistent with previous studies.4,5,9,10 Objectives To compare the efficacy and safety of bimekizumab with ustekinumab and placebo in patients with moderate to severe plaque psoriasis treated for one year. Background Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. Both of these interleukins are implicated in the immunopathogenesis of psoriasis.1–3 Bimekizumab led to substantial clinical improvements in patients with moderate to severe plaque psoriasis (PSO) in the phase 2 BE ABLE study, with no unexpected safety findings.4,5 Methods Adult patients with moderate to severe PSO were enrolled in the pivotal phase 3 BE VIVID study (NCT03370133), a randomized, double-blinded superiority study in which patients were treated with bimekizumab, ustekinumab, or placebo (Figure 1). • The co-primary endpoints were superiority of bimekizumab versus placebo in 90% improvements from baseline in Psoriasis Area and Severity Index (PASI 90) and an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1). • Missing data were imputed with non-responder imputation (NRI). • Treatment emergent adverse events (TEAEs) were classified using MedDRA version 19.0. Results Patient Population • Baseline characteristics are shown in Table 1. Efficacy • At Week 16, the proportions of patients receiving bimekizumab who achieved PASI 90 and IGA 0/1 were significantly greater than for ustekinumab or placebo (Figure 2). • Response was rapid, with 76.9% of bimekizumab-treated patients achieving PASI 75 at Week 4, compared to 15.3% for ustekinumab and 2.4% for placebo (p<0.001 vs ustekinumab and placebo). Safety • Overall, bimekizumab was well-tolerated and discontinuation due to TEAEs was low (Table 2). • The vast majority of the oral candidiasis cases were localized, mild or moderate superficial infections, and did not lead to discontinuation (Table 2). • All incidences of major adverse cardiac events (MACE) occurred in patients with ≥2 pre-existing cardiovascular risk factors (Table 2). • Overall incidence of MACE across the bimekizumab in PSO clinical program (phase 2/phase 3/open-label extension to Nov 1, 2019) was 0.66/100 patient-years and consistent with the background risk within the PSO population and incidence for other anti-IL biologics.6–8 K. Reich,1 K.A. Papp,2 A. Blauvelt,3 R. Langley,4 A. Armstrong,5 R.B. Warren,6 K. Gordon,7 J.F. Merola,8 C. Madden,9 M. Wang,9 V. Vanvoorden,10 M. Lebwohl11 Figure 1 Study design Author Affiliations: 1Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf and Skinflammation® Center, Hamburg, Germany; 2Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 3Oregon Medical Research Center, Portland, OR, USA; 4Dalhousie University, Halifax, NS, Canada; 5Keck School of Medicine of USC, Dermatology, Los Angeles, CA, USA; 6The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, UK; 7Medical College of Wisconsin, Milwaukee, WI, USA; 8Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; 9UCB Pharma, Raleigh, NC, USA; 10UCB Pharma, Brussels, Belgium; 11Icahn School of Medicine, New York, NY, USA. Presented at Fall Clinical Dermatology Conference 2020 | October 29–November 1 | Las Vegas, NV Efficacy and Safety of Bimekizumab in Patients with Moderate to Severe Plaque Psoriasis: Results from BE VIVID, a 52-Week Phase 3, Randomized, Double-Blinded, Ustekinumab- and Placebo-Controlled Study References: 1Durham L. Curr Rheumatol Reports 2015;17:55; 2Fujishima S. Arch Dermatol Res 2010;302:499–505; 3Johnston A. et al. J Immunol 2013;190:2252–62; 4Papp K. et al. JAAD 2018;79:277–86, NCT02905006; 5Blauvelt A. et al. AAD 2019 (OP11180), NCT03010527; 6FDA Briefing Document, Dermatologic and Opthalmic Drugs Advisory Committee, July 19 2016; 7Kerkhof PC. et al. JAAD 2016; 75:83–98; 8Australian Public Report for Ixekizumab, May 2017; 9Glatt S. et al. Br J Clin Pharm 2017;83(5):991–1001; 10Glatt S. et al. Ann Rheum Dis 2018;77:523–32. Author Contributions: Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: KR, KAP, AB, RL, AA, RBW, KG, JFM, CM, MW, VV, ML; Drafting of the publication, or revising it critically for important intellectual content: KR, KAP, AB, RL, AA, RBW, KG, JFM, CM, MW, VV, ML; Final approval of the publication: KR, KAP, AB, RL, AA, RBW, KG, JFM, CM, MW, VV, ML. Author Disclosures: KR: Served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Covagen, Dermira Inc., Eli Lilly, Forward Pharma, Fresenius Medical Care, Galapagos, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB Pharma, Valeant, and Xenoport. KAP: Honoraria and/or grants from AbbVie, Akros, Amgen, Arcutis, Astellas, Baxalta,Boehringer Ingelheim, Bristol-Myers Squibb, Canfite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Gilead, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Merck Sharp & Dohme, Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma, and Valeant/Bausch Health; Consultant (no compensation) for AstraZeneca and Meiji Seika Pharma. AB: Served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira Inc., Eli Lilly, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma, and as a paid speaker for AbbVie. RL: Honoraria from AbbVie, Amgen, Centocor, Pfizer, Janssen Pharmaceuticals, LEO Pharma, Boehringer Ingelheim, Eli Lilly, and Valeant Pharmaceuticals for serving as an advisory board member, principal investigator, and speaker. AA: Research investigator and/or consultant for AbbVie, Bristol-Myers-Squibb, Dermavant, Dermira Inc., Eli Lilly, Janssen, LEO Pharma, KHK, Modernizing Medicine, Novartis, Ortho Dermatologics, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, RBW: Research grants and/or consulting fees from AbbVie, Almirall, Amgen, Arena, Avillion, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma. KG: Honoraria and/or research support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira Inc., Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma. JFM: Consultant and/or investigator for AbbVie, Aclaris, Almirall, Amgen, Biogen, Celgene, Dermavant, Eli Lilly, GlaxoSmithKline, Incyte, Kiniksa, Janssen, Mallinckrodt, Merck, Momenta, Novartis, Pfizer, Samumed, Sanofi Regeneron, Science 37, Sun Pharma, and UCB Pharma; Speaker’s bureau for AbbVie. CM, MW, VV: Employees of UCB Pharma. ML: Employee of Mount Sinai which receives research funds from: AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, LEO Pharma, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB Pharma, Inc., and ViDac. Consultant for Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance, and Verrica. Acknowledgements: This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Susanne Wiegratz, MSc, UCB Pharma, Monheim am Rhein, Germany and Eva Cullen, PhD, UCB Pharma, Brussels, Belgium for publication coordination and critical review, Daniel Smith, BA (Hons), Costello Medical, Cambridge, UK, for medical writing and editorial assistance, and the Costello Medical Design Team for design support. All costs associated with development of this poster were funded by UCB Pharma in accordance with the Good Publication Practice (GPP3) guidelines. aUstekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections. Synopsis Patients were randomized 4:1:2 to receive bimekizumab every four weeks, placebo or ustekinumab Methods To compare the efficacy and safety of bimekizumab with ustekinumab and placebo in patients with moderate to severe plaque psoriasis Objective BE VIVID met both of its co-primary endpoints at Week 16, with significantly higher PASI 90 and IGA 0/1 responder rates vs placebo; superiority vs ustekinumab was also demonstrated Results Bimekizumab was superior to ustekinumab and placebo in PASI 90 and IGA 0/1 at Week 16, and was generally well tolerated with a safety profile consistent with phase 2 studies Conclusion Table 1 Baseline characteristics Figure 2 Responder rates over 52 weeks (ITT, NRI) Table 2 Safety BSA: body surface area; DLQI: Dermatology Life Quality Index; IGA 0/1: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement relative to Baseline in Investigator’s Global Assessment, scored on a 5-point scale; IL: interleukin; ITT: intent-to-treat; LFT: liver function test; MACE: major adverse cardiac events; NEC: not elsewhere classified; NRI: non-responder imputation; PASI: Psoriasis Area Severity Index; PSO: psoriasis; Q4W: every 4 weeks; Q12W: every 12 weeks; SD: standard deviation; SIB: suicide-ideation behaviors; TEAEs: treatmentemergent adverse events; TNF: tumor necrosis factor. aUstekinumab (Q12W) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bIncludes patients switching from placebo to bimekizumab 320 mg Q4W at Week 16; only events occurring after switching are included in this column; cOne esophageal adenocarcinoma; dOne gastric cancer; eOne basal cell carcinoma; fHypersensitivity reactions were predominantly cutaneous and subcutaneous, with no cases of anaphylaxis in any treatment group; gIncidence of LFT elevations among bimekizumab-treated patients was generally low and comparable to placebo and ustekinumab; hAll fungal infections not classified as Candida or Tinea were classified as fungal infections NEC; iIn addition, all opportunistic infections were localized mucocutaneous fungal infections defined as opportunistic by convention; there were no systemic opportunistic infections or cases of active tuberculosis reported. aUstekinumab (Q12W) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; *p<0.001 vs placebo; †p<0.001 vs ustekinumab; ‡nominal p<0.001 vs placebo; §nominal p<0.001 vs ustekinumab. p values for the comparison of treatment groups were based on the Cochran–Mantel–Haenszel test from the general association; nominal p values for the general association were based on a stratified Cochran–Mantel–Haenszel test where region and prior biologic exposure were used as stratification variables and were not controlled for multiplicity. At Week 16, patients receiving placebo were switched to bimekizumab 320 mg Q4W. A rapid response was observed, with over 75% of bimekizumab- treated patients achieving PASI 75 at Week 4, after only one dose A) PASI 90 B) IGA 0/1 C) PASI 100 Initial Period (Weeks 0–16) Initial and Maintenance Periods (Weeks 0–52) Placebo (n=83) n (%) Bimekizumab 320 mg Q4W (n=321) n (%) Ustekinumaba (n=163) n (%) Bimekizumab 320 mg Q4Wb (n=395) n (%) Ustekinumaba (n=163) n (%) Incidence of TEAEs Any TEAE 39 (47.0) 181 (56.4) 83 (50.9) 323 (81.8) 130 (79.8) Serious TEAEs 2 (2.4) 5 (1.6) 5 (3.1) 24 (6.1) 12 (7.4) Discontinuation due to TEAEs 6 (7.2) 6 (1.9) 3 (1.8) 21 (5.3) 7 (4.3) Drug-related TEAEs 8 (9.6) 79 (24.6) 19 (11.7) 147 (37.2) 33 (20.2) Severe TEAEs 3 (3.6) 5 (1.6) 3 (1.8) 20 (5.1) 8 (4.9) Deaths 1 (1.2) 1 (0.3) 1 (0.6) 2 (0.5) 1 (0.6) Common TEAEs (>5% of Patients) Nasopharyngitis 7 (8.4) 30 (9.3) 14 (8.6) 86 (21.8) 36 (22.1) Oral candidiasis 0 28 (8.7) 0 60 (15.2) 1 (0.6) Upper respiratory tract infection 2 (2.4) 9 (2.8) 5 (3.1) 36 (9.1) 18 (11.0) Urinary tract infection 5 (6.0) 6 (1.9) 2 (1.2) 12 (3.0) 7 (4.3) Back pain 2 (2.4) 3 (0.9) 4 (2.5) 10 (2.5) 9 (5.5) Headache 0 11 (3.4) 7 (4.3) 16 (4.1) 9 (5.5) Hypertension 1 (1.2) 7 (2.2) 5 (3.1) 14 (3.5) 10 (6.1) Safety Topics of Interest Inflammatory bowel disease 0 1 (0.3) 0 1 (0.3) 0 Adjudicated SIB 0 0 0 1 (0.3) 1 (0.6) Malignancies 1 (1.2)c 0 0 1 (0.3)d 1 (0.6)e Neutropenia 0 2 (0.6) 0 4 (1.0) 1 (0.6) Hypersensitivity reactionsf 0 16 (5.0) 10 (6.1) 47 (11.9) 15 (9.2) Adjudicated MACE 0 1 (0.3) 0 5 (1.3) 0 Acute myocardial infarction 0 0 0 1 (0.3) 0 Cardiac arrest 0 1 (0.3) 0 1 (0.3) 0 Myocardial infarction 0 0 0 2 (0.5) 0 Cerebral infarction 0 0 0 1 (0.3) 0 Hepatic events 1 (1.2) 4 (1.2) 0 10 (2.5) 4 (2.5) Liver function analysesg 1 (1.2) 4 (1.2) 0 8 (2.0) 4 (2.5) Fungal infectionsh,i 0 45 (14.0) 1 (0.6) 92 (23.3) 4 (2.5) Candida infections 0 33 (10.3) 0 72 (18.2) 1 (0.6) Tinea infections 0 5 (1.6) 0 11 (2.8) 1 (0.6) PBO/bimekizumab 320 mg Q4W (n=83) Bimekizumab 320 mg Q4W (n=321) Ustekinumaba (n=163) Age (years), mean ± SD 49.7 ± 13.6 45.2 ± 14.0 46.0 ± 13.6 Male, n (%) 60 (72.3) 229 (71.3) 117 (71.8) Caucasian, n (%) 63 (75.9) 237 (73.8) 120 (73.6) Weight (kg), mean ± SD 89.1 ± 26.4 88.7 ± 23.1 87.2 ± 21.1 Duration of PSO (years), mean ± SD 19.7 ± 13.8 16.0 ± 11.6 17.8 ± 11.6 PASI, mean ± SD 20.1 ± 6.8 22.0 ± 8.6 21.3 ± 8.3 BSA (%), mean ± SD 27.0 ± 16.3 29.0 ± 17.1 27.3 ± 16.7 IGA, n (%)b 3: moderate 54 (65.1) 201 (62.6) 96 (58.9) 4: severe 28 (33.7) 119 (37.1) 66 (40.5) DLQI total, mean ± SD 10.0 ± 6.8 9.9 ± 6.3 11.0 ± 6.9 Any prior systemic therapy, n (%) 64 (77.1) 267 (83.2) 132 (81.0) Prior biologic therapy, n (%) 33 (39.8) 125 (38.9) 63 (38.7) anti-TNF 16 (19.3) 51 (15.9) 24 (14.7) anti-IL-17 18 (21.7) 76 (23.7) 38 (23.3) anti-IL-23 5 (6.0) 16 (5.0) 6 (3.7) aUstekinumab (Q12W) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bIn each treatment group, one patient with mild IGA score was mistakenly enrolled. Previously presented at AAD 2020 n=321 n=163 n=83 Week 16Baseline Week 52 2–5 weeks Bimekizumab 320 mg Q4W Bimekizumab 320 mg Q4W Placebo Ustekinumab 45/90 mg Q12Wa 20 weeks after last dose: safety follow-up Open-label extension study (BE BRIGHT) 4:1:2 randomization N=567 Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 Screening Initial treatment period Active comparator period Maintenance period 25 75 50 0 100 P ro p o rt io n o f p a ti e n ts a c h ie vi n g P A S I 9 0 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 4.8% 49.7% 55.8% 81.6%† 85.0%*† 2.4% 3.1% 43.6%‡§ p<0.001p<0.001 25 75 50 0 100 P ro p o rt io n o f p a ti e n ts a c h ie vi n g I G A 0 /1 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 77.9%† 60.7% 4.8%2.4% 12.9% 53.4% 49.8%‡§ 84.1%*† p<0.001p<0.001 25 75 50 0 100 P ro p o rt io n o f p a ti e n ts a c h ie vi n g P A S I 10 0 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 38.0% 64.2%§ 58.6%*§ 20.9% 0%1.2% 15.0% p<0.001 p<0.001 Ustekinumaba (n=163) Bimekizumab 320 mg Q4W (n=321)Placebo (n=83) 2.4% Week Week Week Week 16 IGA 0/1 Proportion of patients achieving IGA 0/1 (%) Week 16 PASI 90 Proportion of patients achieving PASI 90 (%) Ustekinumab (n=163) 4.8% 4.8% Bimekizumab 320 mg Q4W (n=321) 84.1% Placebo (n=83) Ustekinumab (n=163) Bimekizumab 320 mg Q4W (n=321) Placebo (n=83) 85.0% 49.7% 53.4% p<0.001 p<0.001 p<0.001 p<0.001