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Abstract Number: L19

Ianalumab (VAY736), a Dual Mode of Action Biologic Combining BAFF Receptor Inhibition with B Cell Depletion, for Treatment of Primary Sjögren’s Syndrome: Results of an International Randomized, Placebo Controlled Dose Range Finding Study in 190 Patients

Simon Bowman1, Robert Fox 2, Thomas Dörner 3, Xavier Mariette 4, Athena Papas 5, Thomas Grader-Beck 6, Benjamin A. Fisher 7, Filipe Barcelos 8, Salvatore De Vita 9, Hendrik Schulze-Koops 10, Robert J. Moots 11, Guido Junge 12, Janice Woznicki 13, Monika Sopala 12, Wen-Lin Luo 13 and Wolfgang Hueber 12, 1University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, 2Scripps Memorial Hospital and Research Institute, La Jolla, California, 3Charite Universitätsmedizin Berlin and DRFZ, Berlin, Germany, 4Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France, 5Tufts School of Dental Medicine, Massachusetts, 6Johns Hopkins University, Baltimore, 7University Hospitals Birmingham NHS Foundation Trust, Birmingham Biomedical Research Centre, Birmingham, United Kingdom, 8Nova Medical School, Hospital Cuf Descobertas, Instituto Português de Reumatologia,, Lisbon, Portugal, 9Rheumatology Clinic, Udine University Hospital, Department of Medical Area, University of Udine, Udine, Italy, Udine, Italy, 10Department of Rheumatology/Clinical Immunology, Ludwig-Maximilians-University Munich, Munich, Germany, 11Institute of Ageing and Chronic Disease, Liverpool, United Kingdom, 12Novartis Pharma AG, basel, Switzerland, 13Novartis Pharmaceuticals Corporation, New Jersey

Meeting: 2019 ACR/ARP Annual Meeting

Date of first publication: October 23, 2019

Keywords: autoimmune diseases, BAFF, Biologic agents, Immunoglobulin (IG), Late-Breaking 2019

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Session Information

Date: Tuesday, November 12, 2019

Session Title: 5T132: Late-Breaking Abstracts

Session Type: Late-Breaking Abstract Session

Session Time: 4:00PM-6:00PM

Background/Purpose: Primary Sjogren’s syndrome (pSS) is a multi-organ autoimmune disease primarily affecting excretory glands and characterized by B-cell hyperactivity. No approved systemic treatments are available. Ianalumab (VAY736) is an anti-B-cell activating factor (BAFF) receptor fully human IgG1 monoclonal antibody, engineered for direct ADCC-mediated B-cell depletion, thus providing a dual mode of action and targeted approach to treat pSS. The current phase 2b study aimed at establishing a dose-response relationship over a wide range of VAY736 doses, using change from baseline (BL) in the EULAR Sjogren’s Syndrome Disease Activity index (ESSDAI) over 24 Weeks (Wks) as the primary endpoint. Here we report Wk24 efficacy and safety. The study is ongoing with a second blinded treatment period up to Wk52.

Methods: 190 patients with pSS were randomized 1:1:1:1 to monthly s.c. administrations of placebo (PBO) or one of three VAY736 doses; 5mg, 50mg and 300mg. First-dose premedication was 250mg IV methylprednisolone. To be eligible, patients had to fulfill the American European Consensus Group (AECG) criteria for pSS, be anti-Ro/SSA positive, have an ESSDAI ≥6 (on 7/12 domains: glandular, articular, lymphadenopathy, constitutional, cutaneous, hematologic, biologic), and EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) ≥5. Statistical methods included MCP-Mod to assess the dose-response on change of ESSDAI (12 domains) from BL and responder analysis to calculate the proportion of patients with ≥3 points improvement on ESSDAI as secondary analysis. Secondary endpoints included ESSPRI, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Physician’s (PhGA) and Patient’s Global Assessments (PGA), SF-36, stimulated salivary flow (sSF) and Schirmer’s test.

Results: The primary endpoint of the study was met with a statistically significant dose-response for ESSDAI (Figure 1). The largest reduction in ESSDAI was 1.92 points over PBO for VAY736 300mg at Wk24. Secondary analysis on ESSDAI revealed for 300mg vs PBO responder rates of 42/47 (89.4%) vs 30/49 (61.2%), a difference of 28.1% (p=0.0019), while no differences were seen for 5mg and 50mg vs PBO. Consistent with this result, PhGA change from BL was significantly different between VAY736 300mg and PBO (p=0.022). A numerical trend for improvement of sSF for VAY736 300mg compared to PBO was notable at Wk24 (p=0.092). However, the secondary efficacy endpoints ESSPRI and FACIT-F showed no benefits over PBO for improvements in the burden of illness. PBO responses were generally high. Incidence of treatment emergent adverse events were comparable across PBO and active groups, whereby local injection reactions were most frequent, mostly mild and showed a dose-response.

Conclusion: The defined primary endpoint assessing ESSDAI was met, showing statistically significant dose-response for ianalumab with clinically important improvement over placebo at the highest tested dose. The preliminary safety profile was good. Future analysis will focus on PK and immunogenicity, salivary and tear flow parameters and the exploration of ESSDAI domains, and the ongoing-blinded treatment period up to Week 52.

ESSDAI Change from Baseline over Time up to Week 24 Reveals a Statistically Significant Dose Response Relationship


Disclosure: S. Bowman, AstraZeneca, 1, Biogen, 1, BMS, 1, Celgene, 1, Medimmune, 1, MTPharma, 1, Novartis, 1, ONO, 1, UCB, 1, Xtlbio, 1; R. Fox, Novartis, 1, Pfizer, 1, Lilly, 1; T. Dörner, AbbVie, 5, Celgene, 5, Eli Lilly and Company, 5, 8, GSK, 2, Janssen, 2, 5, Novartis, 2, 5, Novartis Pharma AG, 5, Roche, 5, 8, Samsung, 5, 8, Sanofi, 2, UCB, 5, UCB Pharma, 2, 5; X. Mariette, Biogen, 2, Bristol-Myers Squibb, 5, GlaxoSmithKline, 5, Janssen, 5, LFB Pharmaceuticals, 5, OSE Immunotherapeutics, 2, Pfizer, 2, 5, UCB Pharma, 5, 8; A. Papas, Novartis, 1, 2; T. Grader-Beck, None; B. Fisher, Novartis, 1, Roche, 1, BMS, 1; F. Barcelos, None; S. De Vita, None; H. Schulze-Koops, Eli Lilly and Company, 1, 2, AbbVie, 1, 2, Amgen, 1, 2, Biogen, 1, 2, Hexal-Sandoz, 1, 2; R. Moots, Biogen, 2, 5, 8, Bristol-Myers Squibb, 2, 5, 8, Chugai, 2, 5, 8, Novartis, 2, 5, 8, Pfizer Inc, 2, 5, 8, Roche, 2, 5, 8, Sandoz, 2, 5, 8, UCB, 2, 5, 8; G. Junge, Novartis, 1, 2; J. Woznicki, Novartis, 1, 2; M. Sopala, Novartis, 1, 2; W. Luo, Novartis, 1, 2; W. Hueber, Novartis, 1, 2.

To cite this abstract in AMA style:

Smolen J, Nash P, Tahir H, Schulze-Koops H, Li L, Hojnik M, Gellett A, Liu-Leage S, Pillai S, Mease P. Ianalumab (VAY736), a Dual Mode of Action Biologic Combining BAFF Receptor Inhibition with B Cell Depletion, for Treatment of Primary Sjögren’s Syndrome: Results of an International Randomized, Placebo Controlled Dose Range Finding Study in 190 Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/ianalumab-vay736-a-dual-mode-of-action-biologic-combining-baff-receptor-inhibition-with-b-cell-depletion-for-treatment-of-primary-sjogrens-syndrome-results-of-an-international-randomized/. Accessed February 6, 2020.
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