Summary Presented at the 42nd Annual Fall Clinical Dermatology Conference | Las Vegas, NV | October 20–23, 2022 Objective To report long-term infection rates in patients with moderate to severe plaque psoriasis receiving bimekizumab (BKZ) 320 mg every four weeks (Q4W) or every eight weeks (Q8W), pooled to include 2 years of treatment across five phase 3/3b trials, the largest two-year data pool for BKZ in plaque psoriasis. Introduction • BKZ is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)- 17F in addition to IL-17A.1 • Psoriasis is a chronic disease requiring long-term management; therefore, it is important to assess the long-term safety of treatments, including infection rates. Materials and Methods • Rates of infection for treatment-emergent adverse events (TEAEs) over a two-year period were evaluated for all patients who received ≥1 BKZ dose in BE SURE, BE VIVID, BE READY, their open-label extension (OLE) BE BRIGHT (data cut-off: November 9, 2020), or BE RADIANT (data cut-off: April 20, 2021).2–6 • Rates of infection TEAEs were also evaluated separately for patients who were receiving BKZ dosed 320 mg Q4W or Q8W at the time of the TEAE. • TEAEs were coded using MedDRA, Medical Dictionary for Regulatory Activities v19.0. • Data are reported as exposure-adjusted incidence rates (EAIRs), defined as incidence of new cases reported per 100 patient-years (PY), and are presented with 95% confidence intervals (CIs). Results • Overall infection rates decreased over Year 2 relative to Year 1 and were lower in Q8W- versus Q4W-treated patients (Table 1). • The most common infections seen with BKZ were nasopharyngitis, oral candidiasis, and upper respiratory tract infections (Table 2). • No cases of active tuberculosis were reported over the two-year period. Serious infections • Rates of serious infections were low across BKZ-treated patients (Table 3). • The most common serious infections were appendicitis and cellulitis; four events of each occurred. Fungal infections • The majority of fungal infections were Candida infections, most of which were oral candidiasis (Table 4). • Rates of oral candidiasis were lower in Q8W- versus Q4W-treated patients (Figure 1; Table 4); cumulative two-year rates were lower than rates for Year 1 (Table 4). • Over two years, approximately 80% of patients experienced no oral candidiasis events. In patients who did experience such events, most had either one or two (Figure 2). • The vast majority of oral candidiasis events over two years (98.1%) were mild or moderate. • Five BKZ Q4W-treated patients discontinued BKZ due to oral candidiasis in Year 1 versus none in Year 2; no Q8W-treated patients discontinued due to oral candidiasis. Opportunistic infections • Rates of opportunistic infections were low (Table 1); almost all were localized mucocutaneous fungal infections pre-defined as opportunistic by company convention. • Exceptions to the above included one serious case each of ophthalmic herpes zoster (resolved with treatment; did not lead to discontinuation) and systemic candidiasis (resolved; patient discontinued following the event and associated pyelonephritis and obstructive nephropathy). Conclusions Over two years of BKZ treatment, EAIRs of infection TEAEs and pre-defined infections of interest, including oral candidiasis, were generally lower in patients treated with BKZ Q8W compared with Q4W. Infection rates decreased with longer duration of BKZ exposure. Rates of discontinuation due to infections were low. There were no new safety findings with long-term exposure to BKZ. A. Armstrong,1 R.G. Langley,2 K.B. Gordon,3 R.B. Warren,4 D. Thaçi,5 L. Stein Gold,6 L. Peterson,7 C. Madden,7 N. Nunez Gomez,8 D. de Cuyper,9 A. Costanzo10 Bimekizumab infection rates in patients with moderate to severe plaque psoriasis: Analysis of pooled data from 2 years of treatment in phase 3 and 3b clinical trials Previously presented at SPIN 2022 Institutions: 1Keck School of Medicine of USC, Dermatology, Los Angeles, California, USA; 2Dalhousie University, Halifax, Nova Scotia, Canada; 3Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 4Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK; 5Comprehensive Centre for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 6Henry Ford Health System, Detroit, Michigan, USA; 7UCB Pharma, Raleigh, North Carolina, USA; 8UCB Pharma, Monheim, Germany, 9UCB Pharma, Brussels, Belgium; 10Dermatology, Humanitas Clinical and Research Centre, IRCCS, Rozzano, Milan, Italy. References: 1Papp KA et al. J Am Acad Dermatol 2018;79:277–85; 2Warren RB et al. N Engl J Med 2021;385:130–41, NCT03412747 BE SURE; 3Reich K et al. Lancet 2021;397:487–98, NCT03370133 BE VIVID; 4Gordon KB et al. Lancet 2021;397:475–86, NCT03410992 BE READY; 5ClinicalTrials.gov, NCT03598790 BE BRIGHT; 6Reich K et al. N Engl J Med 2021;385:142–52, NCT03536884 BE RADIANT. Author Contributions: Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: AA, RGL, KBG, RBW, DT, LSG, LP, CM, NNG, DdC, AC; Drafting of the publication, or revising it critically for important intellectual content: AA, RGL, KBG, RBW, DT, LSG, LP, CM, NNG, DdC, AC; Final approval of the publication: AA, RGL, KBG, RBW, DT, LSG, LP, CM, NNG, DdC, AC. Author Disclosures: AA: Served as a research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Boeringer Ingleheim, BMS, Dermavant, Dermira, Eli Lilly, EPI, Incyte, Janssen, LEO Pharma, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. RGL: Principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, and Pfizer. KBG: Received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, BMS, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; research support from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma. RBW: Supported by the NIHR Manchester Biomedical Centre; consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, 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. DT: Honoraria for participation on advisory boards, as a speaker, and for consultancy from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi Genzyme, and UCB Pharma; research grants received from Celgene, LEO Pharma, and Novartis. LSG: Consultant for AbbVie, Amgen, Arcutis, Dermavant, LEO Pharma, Novartis, Pfizer, Sanofi-Regeneron, and UCB Pharma; principal investigator for AbbVie, Arcutis, Dermavant, LEO Pharma, Novartis, and UCB Pharma. LP, CM, NNG, DdC: Employees and shareholders of UCB Pharma. AC: Investigator and/or speaker and/or advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, and UCB Pharma. Acknowledgments: 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 this study. The authors acknowledge Susanne Wiegratz, MSc, UCB Pharma, Monheim, Germany, for publication coordination, Emma Francis-Gregory, BA, Costello Medical, Cambridge, UK, for medical writing and editorial assistance and the Costello Medical design team, for graphic design assistance. Figure 2 Patients with oral candidiasis TEAEs BKZ: bimekizumab; CI: confidence interval; EAIR: exposure-adjusted incidence rate; IL: interleukin; MedDRA: Medical Dictionary for Regulatory Activities; NEC: not elsewhere classified; OLE: open-label extension; PY: patient-years; Q4W: every four weeks; Q8W: every eight weeks; TEAE: treatment-emergent adverse event. Figure 1 EAIRs of oral candidiasis over two years by treatment period and continuous BKZ dosing A) Year 1a For patients who received both BKZ 320 mg Q4W and Q8W doses during the trials, TEAEs were assigned to the dose most recently received prior to the date of onset of the TEAE. Patients who received both BKZ 320 mg Q4W and Q8W at different times in the trials were included in the population count of both treatment groups, but only once in each BKZ Total group. Data were pooled for all patients who received ≥1 BKZ dose in BE SURE, BE VIVID, BE READY, their OLE BE BRIGHT (data cut-off: November 9, 2020), or BE RADIANT (data cut-off: April 20, 2021).2–6 aBE VIVID did not use Q8W dosing; bBE RADIANT is comprised of a 48-week double-blinded study period and an ongoing OLE. Data from both study periods were included here; the trial is included in the total numbers of both double-blinded trials and OLEs. The most common infections were nasopharyngitis, oral candidiasis, and upper respiratory tract infection 98.1% of oral candidiasis events observed over two years were mild or moderate Rates of serious infections were low in all groups and did not increase with longer duration of BKZ exposure B) Cumulative over 2 yearsa 1,767/2,186 (80.8%) patients did not experience any oral candidiasis events over two years. aData are reported from Weeks 0–104 of treatment. 1,836/2,186 (84.0%) patients did not experience any oral candidiasis events over Year 1. aYear 1 includes data from Weeks 0–52 of treatment. Error bars/values in parentheses represent 95% CIs. Data are reported for all patients who received BKZ at Week 16 and received either BKZ Q4W or Q8W continuously during the maintenance period and in the OLE. All patients received BKZ Q4W through Weeks 0–16. aFor Weeks 52–104, N=233 for BKZ Q4W only and N=416 for BKZ Q4W/Q8W only. aYear 1 includes data from Weeks 0–52 of treatment; bYear 2 includes data from Weeks 52–104 of treatment. aYear 1 includes data from Weeks 0–52 of treatment; bYear 2 includes data from Weeks 52–104 of treatment. aYear 1 includes data from Weeks 0–52 of treatment; bYear 2 includes data from Weeks 52–104 of treatment. aYear 1 includes data from Weeks 0–52 of treatment; bYear 2 includes data from Weeks 52–104 of treatment; cThere was one serious, severe case of esophageal candidiasis in a patient receiving BKZ 320 mg Q4W during the first year of treatment which led to discontinuation. Table 1 Overall infection rates Table 2 Most common infections Table 3 Serious infections Table 4 Fungal infections N=2,025 2,329 PY 4 double- blinded trials and 2 OLEsb Dosing Population Exposure Trials administered N=2,186 N=1,576 3,796 PY 1,471 PY BKZ Total BKZ Q4W BKZ Q8Wa 3 double- blinded trials and 2 OLEsb 4 double- blinded trials and 2 OLEsb 50 5 10 15 20 25 30 35 40 45 0 30.5 (19.9, 44.7) 29.7 (21.1, 40.6) 18.2 (12.5, 25.7) 22.9 (17.6, 29.3) 16.1 (11.0, 22.9) 7.2 (4.7, 10.6) BKZ Q4W (N=289)a BKZ Q4W/Q8W (N=446)a Treatment period Weeks 16–52 Weeks 52–104Weeks 0–16 E A IR /1 0 0 P Y 1 Percentage of patients (%)N u m b e r o f o ra l c a n d id ia si s T E A E s e x p e ri e n c e d b y t h e sa m e p a ti e n t 0 10 20 30 40 50 60 70 80 90 100 2 3 4 ≥5 0.3% 0.6% 1.4% 4.1% 9.6% BKZ Total (N=2,186) N u m b e r o f o ra l c a n d id ia si s T E A E s e x p e ri e n c e d b y t h e sa m e p a ti e n t BKZ Total (N=2,186)1 Percentage of patients (%) 0 10 20 30 40 50 60 70 80 90 100 2 3 4 ≥5 1.0% 1.2% 2.1% 4.7% 10.2% 98.1% Year 1a Year 2b Cumulative over two years BKZ Total N=2,186 BKZ Total N=1,710 BKZ 320 mg Q4W N=2,025 BKZ 320 mg Q8W N=1,576 BKZ Total N=2,186 Summary of treatment exposure Total exposure, PY 2,049 1,291 2,329 1,471 3,796 Summary of infection TEAEs, EAIR/100 PY (95% CI) Any infection TEAE 116.8 (110.6, 123.1) 83.7 (77.8, 90.0) 110.2 (104.2, 116.5) 77.7 (71.9, 83.9) 93.9 (89.3, 98.7) Opportunistic infections 1.8 (1.3, 2.5) 0.5 (0.2, 1.1) 1.7 (1.2, 2.3) 0.5 (0.2, 1.0) 1.2 (0.9, 1.6) Staphylococcal infections 1.5 (1.0, 2.1) 0.9 (0.5, 1.6) 1.3 (0.9, 1.9) 0.9 (0.5, 1.5) 1.1 (0.8, 1.5) Streptococcal infections 1.1 (0.7, 1.7) 1.0 (0.5, 1.7) 1.0 (0.6, 1.4) 1.1 (0.6, 1.8) 1.0 (0.7, 1.4) Leading to discontinuation 1.1 (0.7, 1.6) 0.3 (0.1, 0.8) 0.9 (0.6, 1.4) 0.3 (0.1, 0.8) 0.7 (0.5, 1.0) Active tuberculosis 0.0 0.0 0.0 0.0 0.0 Year 1a Year 2b Cumulative over two years BKZ Total N=2,186 BKZ Total N=1,710 BKZ 320 mg Q4W N=2,025 BKZ 320 mg Q8W N=1,576 BKZ Total N=2,186 Most common infection TEAEs, EAIR/100 PY (95% CI) Nasopharyngitis 25.2 (22.9, 27.7) 17.8 (15.4, 20.3) 22.0 (19.9, 24.2) 15.5 (13.5, 17.9) 18.4 (17.0, 20.0) Oral candidiasis 18.4 (16.5, 20.5) 13.3 (11.3, 15.5) 17.1 (15.4, 19.0) 10.5 (8.9, 12.4) 13.0 (11.8, 14.3) Upper respiratory tract infection 10.3 (8.9, 11.8) 7.3 (5.9, 9.0) 8.8 (7.6, 10.2) 7.3 (5.9, 8.8) 7.8 (6.9, 8.8) Year 1a Year 2b Cumulative over two years BKZ Total N=2,186 BKZ Total N=1,710 BKZ 320 mg Q4W N=2,025 BKZ 320 mg Q8W N=1,576 BKZ Total N=2,186 Summary of serious infection TEAEs, EAIR/100 PY (95% CI) Serious infections 1.7 (1.2, 2.3) 0.5 (0.2, 1.1) 1.4 (1.0, 2.0) 0.9 (0.5, 1.5) 1.2 (0.9, 1.6) Most common serious infection TEAEs (four events each over two years), EAIR/100 PY (95% CI) Appendicitis 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.0 (0.0, 0.2) 0.2 (0.0, 0.6) 0.1 (0.0, 0.3) Cellulitis 0.1 (0.0, 0.4) 0.0 0.2 (0.0, 0.4) 0.0 0.1 (0.0, 0.3) Year 1a Year 2b Cumulative over two years BKZ Total N=2,186 BKZ Total N=1,710 BKZ 320 mg Q4W N=2,025 BKZ 320 mg Q8W N=1,576 BKZ Total N=2,186 Summary of fungal infection TEAEs, EAIR/100 PY (95% CI) Fungal infections 29.8 (27.3, 32.5) 22.7 (20.0, 25.6) 27.4 (25.1, 29.9) 19.0 (16.7, 21.6) 21.9 (20.2, 23.6) Candida infections 21.5 (19.4, 23.7) 15.5 (13.4, 17.9) 19.9 (18.0, 21.9) 11.9 (10.1, 13.9) 15.0 (13.6, 16.4) Oral candidiasis 18.4 (16.5, 20.5) 13.3 (11.3, 15.5) 17.1 (15.4, 19.0) 10.5 (8.9, 12.4) 13.0 (11.8, 14.3) Oropharyngeal candidiasis 1.2 (0.8, 1.8) 0.2 (0.0, 0.7) 1.0 (0.7, 1.5) 0.2 (0.0, 0.6) 0.7 (0.5, 1.0) Vulvovaginal candidiasis 1.1 (0.7, 1.6) 0.5 (0.2, 1.0) 1.0 (0.6, 1.4) 0.3 (0.1, 0.8) 0.7 (0.5, 1.0) Skin candidiasis 0.8 (0.5, 1.3) 1.1 (0.6, 1.8) 0.9 (0.5, 1.3) 0.8 (0.4, 1.4) 0.9 (0.6, 1.2) Esophageal candidiasis 0.2 (0.1, 0.6)c 0.0 0.2 (0.0, 0.4)c 0.1 (0.0, 0.4) 0.1 (0.0, 0.3)c Tinea infections 3.8 (3.0, 4.7) 2.4 (1.6, 3.4) 3.2 (2.5, 4.1) 2.9 (2.1, 4.0) 2.9 (2.4, 3.5) Fungal infections NEC 4.5 (3.6, 5.5) 4.7 (3.6, 6.0) 4.2 (3.4, 5.2) 3.4 (2.5, 4.5) 3.7 (3.1, 4.3)