POS0692 IANALUMAB (VAY736) SAFETY AND EFFICACY IN PATIENTS WITH SJOGREN’S SYNDROME: 52 WEEK RESULTS FROM A RANDOMISED, PLACEBO-CONTROLLED, PHASE 2B DOSE-RANGING TRIAL
Authors: T. Dörner, S. J. Bowman, R. Fox, X. Mariette, A. Papas, T. Grader-Beck, B. A. Fisher, F. Barcelos, S. De Vita, H. Schulze-Koops, R. J. Moots, G. Junge, J. Woznicki, M. Sopala, W. L. Luo, W. Hueber
Journal: Annals of the Rheumatic Diseases (2021)

Background: Sjogren’s syndrome (SS) is an autoimmune disease affecting excretory glands and characterised by B-cell hyperactivity. Ianalumab (VAY736) is a human monoclonal antibody to B-cell activating factor receptor, engineered for direct ADCC-mediated B-cell depletion. A Phase 2b study evaluated the dose-response of VAY736 vs placebo (PBO) in EULAR SS Disease Activity Index (ESSDAI) change from baseline (CHB) and other secondary endpoints. Objectives: Primary results at Week (Wk) 24 were reported previously 1 . Here we report 52 Wk safety and efficacy from extended blinded treatment period 2 (TP2). Methods: 190 patients (pts) were randomised equally to receive s.c. doses of VAY736 (5, 50, 300 mg) or PBO every 4 Wks (q4w). Eligible pts fulfilled American European Consensus Group (AECG) criteria, were anti-Ro/SSA+, had ESSDAI ≥6 and EULAR SS Patient Reported Index (ESSPRI) ≥5. At Wk 24, after completion of the first blinded TP (TP1), PBO-treated pts were switched to VAY736 150 mg, and pts on 300 mg were re-randomised to continue 300 mg or PBO for 28 Wks in TP2. Pts were followed post-treatment for ≥20 Wks. Safety was assessed for all periods. Due to lack of PBO-control in TP2, descriptive efficacy analysis was performed for ESSDAI, ESSPRI, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Physician’s (PhGA) and Patient’s Global Assessments (PaGA), SF-36, and SS symptom diary (SSSD). Results: Overall, there was no dose dependency of treatment emergent adverse events (TEAEs) except for injection site reactions, which were mostly mild to moderate in severity. Lymphopenia and neutropenia were mostly grade (G)1 and G2, no G4. Most common TEAEs were infections and infestations in exposure-adjusted analysis of incidence rates. Nasopharyngitis and upper respiratory tract infections were the most common TEAEs, with no dose response (Table 1). Tracheobronchitis and pneumonia, were mild to moderate severity, not associated with absolute neutrophil count G3, and none led to treatment withdrawal. At Wk 52, efficacy was sustained for pts who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA CHB: –9.06, –1.91, –22.03, –35.80, respectively). Efficacy was partially lost for pts switched to PBO at Wk 24 (Figure 1). Improvement was noted for PBO pts switched to 150 mg. Stimulated whole salivary flow at Wk 24 was improved for 300 mg (PBO-adjusted CHB 0.20 ml/min; P=0·037); last measurement at Wk 48 was 0.45 and 0.22 ml/min CHB in pts who continued 300 mg or PBO in TP2, respectively. Conclusion: Ianalumab 300 mg was well tolerated up to 52 Wks. Exploratory efficacy showed that continuous dosing of 300 mg s.c. q4w provided sustained clinical benefit. PaGA was the outcome that showed the most prominent change following switch to PBO or VAY736. References: [1]Dörner T, et al. [OP0302]. Ann Rheum Dis . 2020; 79 (suppl 1). Table 1. Key Safety Data (All Study Periods up to Week 52) * n (% ) [EAIR] 1 5 mg 24 Wks (N=47 ) 50 mg 24 Wks (N=47 ) 150 mg 28 Wks (N=47 ) Any 300 mg (N=47 ) Any AE 43 (91.5 ) 43 (91.5 ) 44 (93.6 ) 45 (95.7 ) [517.5] [423.3] [621.0] [544.6] Any SAE 3 (6.4 ) 5 (10.6 ) 8 (17.0 ) 8 (17.0 ) [5.9] [10.7] [19.9] [13.6] Infections and infestations (SOC ) 2 33 (70.2 ) 31 (66.0 ) 34 (72.3 ) 38 (80.9 ) [154.1] [119.2] [162.0] [127.7] Nasopharyngitis 3 7 [15.5] 4 [8.5] 9 [22.1] 9 [16.5] Upper respiratory tract infections 3 6 [12.8] 8 [17.8] 5 [11.6] 8 [13.6] Bronchitis 3 3 [6.2] 3 [6.2] 4 [9.5] 4 [6.6] Tracheobronchitis 3 1 [2.0] 0 [0.0] 0 [0.0] 3 [5.0] Pneumonia 3 1 [2.0] 0 [0.0] 1 [2.2] 2 [3.3] Blood &amp; Lymphatic Disorders (SOC ) 2 8 (17.0 ) 9 (19.1 ) 6 (12.8 ) 9 (19.1 ) [18.0] [20.8] [14.3] [16.8] Lymphopenia 3 4 [8.4] 4 [8.6] 3 [6.8] 2 [3.3] Neutropenia 3 5 [10.7] 1 [2.1] 2 [4.5] 4 [6.9] Injection site reaction 3 4 (8.5 ) 9 (19.1 ) 17 (36.2 ) 27 (57.4 ) *Includes all safety data from TP1, TP2 and post-treatment follow-up; cut-off 06-Feb-2020 1 EAIR, incidence rate per 100 subject years. For patient with an event, exposure time is censored at time of first event; 2 Number of pts with at least one AE in SOC; 3 PT, preferred term; SOC, system organ class Disclosure of Interests: Thomas Dörner Consultant of: Novartis, GSK, Sanofi, Janssen, Eli Lilly, Grant/research support from: Deutsche Forschungsgemeinschaft, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Robert Fox Consultant of: Novartis, Pfizer and Lilly, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Medimmune, GSK, Grant/research support from: Servier, Athena Papas Consultant of: Novartis, Grant/research support from: Novartis, Thomas Grader-Beck Consultant of: Novartis, Lilly, Grant/research support from: Abbvie, Celgene, Ben A Fisher Consultant of: Novartis, Roche, BMS and Servier, Filipe Barcelos Consultant of: Pfizer and Lilly, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Hendrik Schulze-Koops Consultant of: Novartis, Robert J Moots Consultant of: Amgen, Chugai, Gilead, Lilly, Novartis, Pfizer, Roche, Grant/research support from: Amgen, Chugai, Gilead, Lilly, Novartis, Pfizer, Roche, Guido Junge Shareholder of: Novartis, Employee of: Novartis, Janice Woznicki Shareholder of: Novartis, Employee of: Novartis, Monika Sopala Shareholder of: Novartis, Employee of: Novartis, Wen-Lin Luo Shareholder of: Novartis, Employee of: Novartis, Wolfgang Hueber Shareholder of: Novartis, Employee of: Novartis