Objectives To evaluate efficacy and safety of bimekizumab (BKZ) in patients with moderate plaque psoriasis over two years using data from five phase 3/3b trials. Introduction • BKZ has demonstrated high levels of efficacy in patients with moderate to severe plaque psoriasis.1–4 • Here, we consider BKZ efficacy and safety in patients with moderate psoriasis. Materials and Methods • Moderate psoriasis was defined as body surface area (BSA) ≥10%–≤15%, Psoriasis Area and Severity Index (PASI) ≥12, and Investigators Global Assessment (IGA)=3 at baseline. • Data were pooled from BE SURE, BE VIVID, BE READY, the first year of the BE BRIGHT open label extension (OLE), and BE RADIANT (48-week double-blinded period and ongoing OLE).1–5 • Patients received BKZ 320 mg every 4 weeks (Q4W) to Week 16, then either BKZ Q4W or every 8 weeks (Q8W) maintenance dosing (Figure 1). • Efficacy outcomes are reported through two years for all BKZ treated patients, regardless of dosing regimen. • Data are reported using modified non-responder imputation (mNRI), NRI, and as the observed case (OC). – For mNRI, patients who discontinued due to lack of efficacy, entered the BE READY open-label escape arm, or discontinued treatment due to an adverse event (AE) prior to OLE entry were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data. • Treatment-emergent AEs (TEAEs), evaluated as exposure-adjusted incidence rates (EAIRs) per 100 patient-years, are reported for patients with moderate psoriasis who received ≥1 BKZ dose. The percentage of patients who experienced a TEAE is also reported. Results • At baseline, 301 patients with moderate psoriasis were randomized to BKZ; 269 continued to the OLEs. • Baseline characteristics for patients with moderate psoriasis were similar to the BKZ-randomized study population with moderate to severe plaque psoriasis (except for criteria used to distinguish between moderate and moderate to severe psoriasis; Table 1). • High levels of PASI ≤2, PASI 100, and BSA ≤1% responses were observed in BKZ-treated patients at Week 16. Similarly high response levels were reported after two years of treatment (OLE Week 48) among patients who entered the OLEs (Figure 2). • TEAEs occurred in 90.7% of patients and were lower with BKZ Q8W vs Q4W. Serious TEAEs and TEAEs leading to discontinuation were low (Table 2). • The most common TEAEs were nasopharyngitis, oral candidiasis, and upper respiratory tract infections (Table 2; Table 3). • Oral candidiasis EAIRs were lower with BKZ Q8W vs Q4W. The majority of oral candidiasis TEAEs were mild/moderate (98.2%). Two patients with oral candidiasis discontinued BKZ. • Similar to the overall study population,6 EAIRs of safety topics of interest were low in moderate psoriasis patients (Table 2; Table 3). • Occurrence of TEAEs and serious TEAEs generally decreased or remained comparable over time (Table 3). Summary Presented at the 42nd Annual Fall Clinical Dermatology Conference | Las Vegas, NV | 20–23 October 2022 Conclusions Results demonstrate that continuously high levels of skin clearance were seen with BKZ over two years in patients with moderate psoriasis. BKZ was well-tolerated over two years in patients with moderate psoriasis. Andrew Blauvelt,1 Linda Stein Gold,2 Melinda Gooderham,3 Bruce Strober,4 Andreas Pinter,5 Jose-Manuel Carrascosa,6 Paolo Gisondi,7 Jonathan Bleier,8,9 Cynthia Madden,10 Delphine Deherder,11 Natalie Nunez Gomez,12 Richard B. Warren13 Bimekizumab efficacy and safety through two years in patients with moderate psoriasis: Analysis of pooled data from five phase 3/3b clinical trials Previously presented at EADV 2022 Institutions: 1Oregon Medical Research Center, Portland, Oregon, USA; 2Henry Ford Health System, Detroit, Michigan, USA; 3SKiN Centre for Dermatology, Probity Medical Research, Peterborough, Ontario, Canada and Queen’s University, Kingston, Ontario, Canada; 4Yale University, New Haven, Connecticut, USA and Central Connecticut Dermatology Research, Cromwell, Connecticut, USA; 5University Hospital Frankfurt, Frankfurt am Main, Germany; 6Hospital Universitari Germans Trias I Pujol, UAB, IGTP, Badalona, Barcelona, Spain; 7University of Verona, Verona, Italy; 8Veramed, London, UK; 9UCB Pharma, Slough, UK; 10UCB Pharma, Raleigh, North Carolina, USA; 11UCB Pharma, Braine-l’Alleud, Belgium; 12UCB Pharma, Monheim, Germany; 13Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK. References: 1Reich K et al. Lancet 2021;397:487–98, NCT03370133; 2Gordon KB et al. Lancet 2021;397:475–86, NCT03410992; 3Warren RB et al. N Engl J Med 2021;385:130–41, NCT03412747; 4Reich K et al. N Engl J Med 2021;385:142–52, NCT03536884; 5BE BRIGHT: clinicaltrials.gov/ct2/show/NCT03598790; 6Gordon KB et al. JAMA Dermatol 2022; published online ahead of print. Author Contributions: Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: AB, LSG, MG, BS, AP, JMC, PG, JB, CM, DD, NNG, RBW; Drafting of the publication, or revising it critically for important intellectual content: AB, LSG, MG, BS, AP, JMC, PG, JB, CM, DD, NNG, RBW; Final approval of the publication: AB, LSG, MG, BS, AP, JMC, PG, JB, CM, DD, NNG, RBW. Author Disclosures: AB: Served as a speaker, scientific adviser, and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, Vibliome, and Xencor. LSG: Consultant for AbbVie, Amgen, Arcutis, Dermavant, LEO Pharma, Bristol Myers Squibb, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, and UCB Pharma; principal investigator for AbbVie, Arcutis, Dermavant, LEO Pharma, Novartis, and UCB Pharma. MG: Investigator, speaker, consultant, or advisory board member for AbbVie, Amgen, Akros, Arcutis, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Janssen, Kyowa Kirin, MedImmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharmaceuticals, and UCB Pharma. BS: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, Leo, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; Stock Options: Connect Biopharma, Mindera Health; Speaker: AbbVie, Eli Lilly, Janssen, Regeneron, and Sanofi-Genzyme; Scientific Co-Director (consulting fee): CorEvitas (formerly Corrona) Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis; Editor-in-Chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis. AP: Investigator and/or speaker and/or advisor for AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi Pharma, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, Schering-Plough, Tigercat Pharma, and UCB Pharma. JMC: Principal/senior investigator and/or consultant and/or advisor for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Sandoz, and UCB Pharma. PG: Consultant for AbbVie, Abiogen, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB Pharma. JB: Veramed statistical consultant for UCB Pharma. CM, DD: Employees and shareholders of UCB Pharma. NNG: Former employee and shareholder of UCB Pharma. RBW: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma; honoraria from Astellas, DiCE, GSK, and Union. Acknowledgements: These studies were funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. The authors acknowledge Susanne Wiegratz, MSc, UCB Pharma, Monheim, Germany for publication coordination, Poppy Wilson, MBiol, Costello Medical, London, UK for medical writing and editorial assistance and the Design team at Costello Medical for graphic design assistance. All costs associated with development of this poster were funded by UCB Pharma. RBW is supported by the NIHR Manchester Biomedical Centre. Figure 1 Study design Figure 2 Efficacy responses for moderate psoriasis patients through two years (mNRI, NRI, OC) AEs: adverse events; BKZ: bimekizumab; BMI: body mass index; BSA: body surface area; DLQI: Dermatology Life Quality Index; EAIR: exposure-adjusted incidence rate; IBD: inflammatory bowel disease; IGA: Investigators Global Assessment; IL: interleukin; MACE: major adverse cardiac events; mNRI: modified non-responder imputation; NRI: non-responder imputation; OC: observed case; OLE: open-label extension; PASI 75/90/100: ≥75%/≥90%/100% improvement from baseline in the Psoriasis Area and Severity Index; Q4W: every 4 weeks; Q8W: every 8 weeks; SD: standard deviation; SIB: suicidal ideation and behavior; TEAE: Treatment-emergent adverse event; TNF: tumour necrosis factor. Table 1 Baseline characteristics Table 2 Summary of TEAEs in moderate psoriasis patients Table 3 Incidence rates of TEAEs by time period A) PASI ≤2 B) PASI 100 C) BSA ≤1 aAnalyses include patients who received open-label escape treatment (BKZ 320 mg Q4W) in BE READY;2 bPatients who achieved ≥PASI 90 at the end of the feeder studies were randomized 4:1 in BE BRIGHT and 1:1 in BE RADIANT to BKZ 320 mg Q4W or Q8W; cWeek numbers correspond to feeder study baseline; OLE Week 48 (two years) corresponds to BE RADIANT Week 96, BE VIVID/BE BRIGHT Week 100, and BE READY/BE BRIGHT and BE SURE/BE BRIGHT Week 104; dIn BE BRIGHT, at OLE Week 24, patients achieving ≥PASI 90 could switch to Q8W at the investigator’s discretion; in BE RADIANT, at OLE Week 16 or the next scheduled clinic visit, patients switched to BKZ Q8W after the implementation of a protocol amendment. aData are reported for all BKZ-treated patients with moderate psoriasis, regardless of dosing regimen; bData are reported for all patients with moderate to severe psoriasis, randomized to BKZ at baseline of the BE SURE, BE VIVID, BE READY, and BE RADIANT phase 3/3b trials who entered the OLEs; cValues in bold are for assessments used to distinguish between moderate and moderate to severe psoriasis. TEAEs were assigned to the dose most recently received prior to the TEAE’s date of onset. Patients who received both BKZ 320 mg Q4W and Q8W at different times in the trials were included in the population count of both groups, but only once in the BKZ Total group. BE RADIANT data cut-off was 20 April 2021; BE BRIGHT data cut-off was 09 Nov 2020. aData reported for all patients with moderate psoriasis who received ≥1 BKZ dose; bProportion of patients reporting at least one TEAE in that category; cNo deaths were assessed as treatment-related. Data are reported for all patients with moderate psoriasis who received ≥1 BKZ dose (BKZ Total). For patients in the BE READY escape arm who then entered BE BRIGHT, their OC assessments were used for OC only, whilst an NRI record which was created at the same visit, even if an OC assessment was present, was used for NRI. aNumber of patients who entered the OLEs; bBE SURE, BE VIVID, and BE READY extended beyond 48 weeks; Week 48 was the last common timepoint; cOLE Week 48 (two years) corresponds to BE RADIANT Week 96, BE VIVID/BE BRIGHT Week 100, and BE READY/BE BRIGHT and BE SURE/BE BRIGHT Week 104. Moderate psoriasis BKZ Totala N=301 Moderate to severe psoriasis BKZ-randomizedb N=1,208 Age (years), mean ± SD 46.3 ± 14.3 45.4 ± 13.8 Male, n (%) 205 (68.1) 844 (69.9) Caucasian, n (%) 271 (90.0) 1,053 (87.2) Weight (kg), mean ± SD 87.9 ± 19.6 89.7 ± 22.0 BMI, mean ± SD 29.3 ± 6.1 29.9 ± 6.8 Duration of psoriasis (years), mean ± SD 17.7 ± 13.4 18.3 ± 12.7 PASI, mean ± SDc 15.7 ± 2.9 20.7 ± 7.5 BSA (%), mean ± SDc 12.9 ± 1.6 26.2 ± 15.6 IGA, n (%)c 3: moderate 301 (100) 793 (65.6) 4: severe 0.0 412 (34.1) DLQI, mean ± SD 10.6 ± 6.3 10.6 ± 6.5 Any prior systemic therapy, n (%) 214 (71.1) 933 (77.2) Prior biologic therapy, n (%) 113 (37.5) 453 (37.5) anti-TNF 51 (16.9) 187 (15.5) anti-IL-17 53 (17.6) 241 (20.0) anti-IL-23 20 (6.6) 64 (5.3) anti-IL-12/23 19 (6.3) 72 (6.0) BKZ Total patientsa N=539 BKZ Q8W patients N=395 BKZ Q4W patients N=499 EAIR (95% CI) n (%)b EAIR (95% CI) n (%)b EAIR (95% CI) n (%)b Any TEAE 224.0 (204.6, 244.7) 489 (90.7) 164.8 (144.9, 186.7) 247 (62.5) 258.1 (233.8, 284.2) 412 (82.6) Serious TEAEs 7.6 (5.9, 9.6) 67 (12.4) 7.9 (5.4, 11.3) 30 (7.6) 7.3 (5.2, 10.0) 38 (7.6) Discontinuation due to TEAEs 3.4 (2.3, 4.8) 31 (5.8) 2.8 (1.4, 5.1) 11 (2.8) 3.7 (2.3, 5.8) 20 (4.0) Severe TEAEs 6.6 (5.0, 8.5) 59 (10.9) 7.1 (4.7, 10.3) 27 (6.8) 6.7 (4.7, 9.3) 35 (7.0) Deathsc 0.3 (0.1, 0.9) 3 (0.6) 0.3 (0.0, 1.4) 1 (0.3) 0.4 (0.0, 1.3) 2 (0.4) Most common TEAEs Nasopharyngitis 21.2 (17.9, 24.8) 154 (28.6) 20.0 (15.4, 25.6) 64 (16.2) 24.4 (20.0, 29.4) 108 (21.6) Oral candidiasis 13.3 (10.9, 16.1) 106 (19.7) 11.8 (8.5, 16.0) 42 (10.6) 17.6 (14.0, 21.9) 83 (16.6) Upper respiratory tract infection 7.8 (6.1, 10.0) 66 (12.2) 8.0 (5.3, 11.4) 29 (7.3) 8.4 (6.1, 11.4) 42 (8.4) Safety topics of interest Serious infections 1.5 (0.8, 2.6) 14 (2.6) 1.0 (0.3, 2.6) 4 (1.0) 2.1 (1.0, 3.7) 11 (2.2) IBD 0.1 (0.0, 0.6) 1 (0.2) 0.0 0.0 0.2 (0.0, 1.0) 1 (0.2) Adjudicated SIB 0.0 0.0 0.0 0.0 0.0 0.0 Malignancies 1.1 (0.5, 2.0) 10 (1.9) 0.8 (0.2, 2.2) 3 (0.8) 1.3 (0.5, 2.7) 7 (1.4) Serious hypersensitivity reactions 0.1 (0.0, 0.6) 1 (0.2) 0.3 (0.0, 1.4) 1 (0.3) 0.0 0.0 Adjudicated MACE 0.3 (0.1, 0.9) 3 (0.6) 0.5 (0.1, 1.9) 2 (0.5) 0.2 (0.0, 1.0) 1 (0.2) Elevated liver enzymes 2.7 (1.7, 3.9) 24 (4.5) 2.9 (1.4, 5.1) 11 (2.8) 2.8 (1.6, 4.7) 15 (3.0) EAIR (95% CI) Weeks 0–16 N=539 Weeks 16–52 N=525 Weeks 52–104 N=443 Any TEAE 339.7 (304.3, 378.2) 226.7 (204.3, 251.0) 170.6 (151.1, 192.0) Serious TEAEs 7.9 (4.2, 13.6) 7.3 (4.7, 10.9) 8.2 (5.4, 12.0) Discontinuation due to TEAEs 4.3 (1.7, 8.8) 3.6 (1.9, 6.3) 3.4 (1.7, 6.1) Severe TEAEs 5.5 (2.5, 10.4) 7.7 (5.0, 11.3) 8.2 (5.3, 12.0) Deaths 0.6 (0.0, 3.4) 0.3 (0.0, 1.7) 0.3 (0.0, 1.7) Most common TEAEs Nasopharyngitis 34.0 (25.4, 44.4) 27.6 (22.0, 34.2) 21.0 (16.1, 27.0) Oral candidiasis 31.6 (23.5, 41.7) 19.1 (14.5, 24.6) 12.2 (8.6, 16.8) Upper respiratory tract infection 10.5 (6.1, 16.7) 12.0 (8.5, 16.5) 6.7 (4.2, 10.2) Percentage of patients achieving PASI outcomes at Week 16 and OLE Week 48 (mNRI) A high proportion of patients with moderate psoriasis achieved PASI 100 at Week 16 and through to two years (OLE Week 48) suggesting that high levels of improvement can be observed regardless of disease severity. P ro p o rt io n o f p a ti e n ts a c h ie v in g P A S I o u tc o m e s (% ) 80 60 40 20 0 100 PASI ≤2 Week 16 OLE Week 48 PASI 100 PASI ≤2PASI 100 66.1 77.7 91.4 95.4 mNRI; N=301 mNRI; N=269 BE SURE, BE VIVID, BE READYa and BE RADIANT1–4 (pooled, double-blinded) BE BRIGHT5 and BE RADIANT (open-label extension) Maintenance period Open-label treatment periodInitial treatment period BKZ 320 mg Q4W N=301 moderate psoriasis patients BKZ 320 mg Q4W BKZ 320 mg Q4W BKZ 320 mg Q4W Week 48 Week 52/56c BE RADIANT BE BRIGHT Week 16 Response assessment OLE Week 0b Week 64 Week 76/80c OLE Week 16/24d Week 96 Week 100/104c OLE Week 48 BKZ 320 mg Q8W