2487: Phase 2 Safety and Efficacy of Subcutaneous (s.c.) Dose Ianalumab (VAY736; Anti-BAFFR mAb) Administered Monthly over 28 Weeks in Patients with Systemic Lupus Erythematosus (SLE) of Moderate-to-Severe Activity

Nan Shen¹, Stanislav Ignatenko², Alexander Gordienko³, Josefina Cortés Hernández⁴, Nancy Agmon-Levin⁵, Pongthorn Narongroeknawin⁶, Katarzyna Romanowska -Prochnicka⁷, Hana Ciferska⁸, Masanari Kodera⁹, James Cheng-Chung Wei¹⁰, Piotr Leszczynski¹¹, Joung-Liang Lan¹², Eduardo Mysler¹³, Rafal Wojciechowski¹⁴, Tunde Tarr¹⁵, Elena Vishneva¹⁶, Yi-Hsing Chen¹⁷, Yuko Kaneko¹⁸, Stephanie Finzel¹⁹, Alberta Hoi²⁰, Ajchara Koolvisoot²¹, Shin-Seok Lee²², Lie Dai²³, Hiroshi Kaneko²⁴, Bernadette Rojkovich²⁵, Lingyun Sun²⁶, Eugeny Zotkin²⁷, Jean-Francois Viallard²⁸, Masao Katayama²⁹, Berta Paula Magallares-Lopez³⁰, Tirtha Sengupta³¹, Carol Sips³² and Stephen J Oliver³², ¹Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University (SJTUSM), Shanghai, China, ²Charité Research Organisation GmbH, Berlin, Germany, ³SM Kirov Military Medical Academy, St. Petersburg, Russia, ⁴Lupus Unit, Rheumatology Department, Vall d’Hebron Hospitals, Barcelona, Spain, ⁵Yabludowicz Center for Autoimmune Disease, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel, ⁶Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand, ⁷Department of Systemic Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland, ⁸Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic, ⁹Department of Dermatology, Japan Community Healthcare Organization Chukyo Hospital, Nagoya, Japan, ¹⁰Chung Shan Medical University Hospital, Department of Rheumatology, Taichung, Taiwan, ¹¹Department of Internal Medicine, Poznan University of Medicine Sciences, Poznan, PL, Poznań, Poland, ¹²China Medical University Hospital, Taichung, Taiwan, ¹³Organizacion Medica de Investigacion, Buenos Aires, Argentina, ¹⁴Department of Rheumatology and Systemic Connective Tissue Diseases, University Hospital No. 2, Bydgoszcz, Poland, ¹⁵Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, ¹⁶LLC Family Clinic, Yekaterinburg, RU, Yekaterinburg, Russia, ¹⁷Taichung Veterans General Hospital, Taichung, Taiwan, ¹⁸Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, ¹⁹Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany, ²⁰Monash University, Department of Medicine, Sub-faculty of Clinical and Molecular Medicine, Melbourne, Australia, ²¹Division of Rheumatology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ²²Chonnam National University Medical School & Hospital, Gwangju, South Korea, ²³Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China, ²⁴Division of Rheumatic Disease, National Center for Global Health and Medicine, Tokyo, Japan, ²⁵Department of Rheumatology and Physiotherapy, Polyclinic of the Hospitaller Brothers of St. John of God, Semmelweis University, Budapest, Hungary, ²⁶Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, ²⁷VA Nasonova Research Institute of Rheumatology, Moscow, Russia, ²⁸CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France, ²⁹National Hospital Organization, Nagoya Medical Center, Nagoya, JP, Nagoya, Japan, ³⁰Department of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain, ³¹Novartis Pharma India, Hyderabad, Hyderabad, India, ³²Novartis Pharma AG, Basel, Switzerland

Background/Purpose: Ianalumab is a novel defucosylated human IgG1 mAb targeting the receptor for B cell Activating Factor belonging to the TNF Family (BAFF-R) providing potent B cell depletion by enhanced antibody-dependent cellular cytotoxicity along with BAFF:BAFF-R signaling blockade.We report safety and efficacy of ianalumab in patients with active SLE.

Methods: This multi-center randomized, parallel group, double-blind placebo-controlled umbrella trial (NCT03656562) enrolled patients (19 Dec 2018 to 31 Jan 2022) having ANA ≥1:80 and meeting ≥4 of 11 ACR 1997 SLE classification criteria, with SLEDAI-2K score ≥6 and BILAG-2004 ≥1 A or ≥2 B scores that included activity in either mucocutaneous and/or musculoskeletal domains. This report is limited to interim analysis results for the fully enrolled ianalumab treatment cohort (active n=34; placebo n=33) completing 28-week blinded treatment period (monthly s.c. injection ianalumab 300 mg or placebo), with measured outcomes at baseline and weeks (w) 4, 8, 12, 16, 24 & 28. Primary w28 outcome was proportion patients meeting composite endpoint requirements consisting of those achieving SLE-Responder Index (SRI)-4 who also tapered predniso(lo)ne to ≤5 mg/d or ≤ baseline dose, whichever was lower, by w16 and kept within that range to w28.Secondary/exploratory outcomes included safety/tolerability, incidence BILAG-2004 moderate or severe flares (≥1 A or ≥2 B), proportion patients achieving Lupus Low Disease Activity State (LLDAS), patient and physician global assessments, and laboratory markers of B cell-associated autoimmune activity.

Results: VAY736 was safe and well-tolerated with no drug-related SAE or dropouts, and one pandemic-related discontinuation in placebo arm. Baseline median(range) values for ianalumab and placebo arms, respectively, were: SLEDAI-2Kscore 10 (6-32) and10 (4-18), and predniso(lo)ne 10 mg (0-30) and 10 mg (0-27.5). Marked depletion of circulating CD19+ B cells was consistently achieved in all ianalumab-treated patients: w28 median 1 cell/uL; range 0-3 (Fig. 3). The mean w28 SRI-4 treatment effect of ianalumab (n=24) over placebo (n=8) was 48.2% (Fig. 1), and that also met the composite primary endpoint was 34.5% (ianalumab n=15; placebo n=3). Reduced incidence of moderate or severe flare was noted for patients treated with ianalumab 44% (n=15) vs placebo 64% (n=21). Benefits of ianalumab over placebo were observed for time-to-moderate or -severe flare and for achieving w28 LLDAS (Fig. 2). Therapeutic responses were also observed for ianalumab- vs placebo-treated subjects on laboratory markers of autoimmune activity (Fig. 3).

Conclusion: Potent B cell depletion was consistently achieved in ianalumab-treated SLE patients that was well tolerated, achieving the primary endpoint of SRI-4 response with sustained steroid reduction, along with substantial treatment benefits on overall SRI-4 response, LLDAS and reductions in moderate and severe flares, and on laboratory markers of autoimmune activity. These positive phase 2 study results support ongoing phase 3 development in lupus of the dual mechanisms of action of ianalumab (SIRIUS-SLE 1 & 2, and SIRIUS-LN).








N. Shen: None; S. Ignatenko: None; A. Gordienko: None; J. Cortés Hernández: GSK, 6; N. Agmon-Levin: AstraZeneca, 1, 6, GlaxoSmithKlein(GSK), 1, 6, Novartis, 1, 6; P. Narongroeknawin: None; K. Romanowska -Prochnicka: None; H. Ciferska: None; M. Kodera: None; J. Wei: Abbvie, 2, 5, 6, Amgen, 5, AstraZeneca, 6, BMS, 2, 5, 6, Celgene, 2, Chugai, 2, 6, Eisai, 2, 6, Eli Lilly, 2, 5, 6, Gilead, 5, GSK, 2, 5, Janssen, 2, 5, 6, Novartis, 2, 5, Pfizer, 2, 5, 6, Sanofi-Aventis, 2, SUN pharma, 5, TSH Taiwan, 2, UCB pharma, 2, 5; P. Leszczynski: AbbVie/Abbott, 6, Eli Lilly, 6, Novartis, 6, Pfizer, 6, Roche, 5, UCB, 5; J. Lan: Annexon Biosciences, 5; E. Mysler: AbbVie, 1, 2, 6, Amgen, 6, AstraZeneca, 1, 5, 6, Bristol Myers Squibb, 5, GSK, 2, 5, Janssen, 1, 5, 6, Lilly, 5, 6, Novartis, 5, Pfizer, 1, 2, 6, Roche, 5, Sandoz, 6; R. Wojciechowski: Eli Lilly, 6, Novartis, 6; T. Tarr: None; E. Vishneva: None; Y. Chen: None; Y. Kaneko: AbbVie/Abbott, 1, 6, Ashai Kasei Pharma, 1, 6, Astellas Pharma, 1, 6, AstraZeneca, 1, 6, AYUMI Pharmacutia, 1, 6, Bristol-Myers Squibb(BMS), 1, 6, Chugai-Pharm, 1, 6, Eisai, 1, 6, Eli Lilly, 1, 6, Gilead Sciences Inc., 1, 6, GlaxoSmithKlein(GSK), 1, 6, Janssen Pharmaceutical KK, 1, 6, Novartis, 1, 6, Pfizer, 1, 6, Tanabe Mitsubishi Pharma, 1, 6, UCB Japan, 1, 6; S. Finzel: AbbVie, 6, AstraZeneca, 2, 6, Chugai, 6, Galapagos, 2, 6, Novartis, 2, Novo Nordisk, 2, UCB, 6; A. Hoi: Abbvie, 6, AstraZeneca, 5, Australian Rheumatology Association, 4, Eli Lilly, 6, EUSA Pharma (UK) Limited, 2, Limbic, 6, Moose Republic, 6, Novartis, 6; A. Koolvisoot: None; S. Lee: None; L. Dai: None; H. Kaneko: None; B. Rojkovich: None; L. Sun: None; E. Zotkin: None; J. Viallard: None; M. Katayama: None; B. Magallares-Lopez: None; T. Sengupta: Novartis, 3; C. Sips: Novartis, 3; S. J Oliver: Novartis, 3, 11.