Safety and Efficacy of Subcutaneous Ianalumab (VAY736) for up to 68 Weeks in Patients with Systemic Lupus Erythematosus: Results from Phase 2 Study

Eduardo Mysler¹, Stanislav Ignatenko², Alexander Gordienko³, Josefina Cortés-Hernández⁴, Nancy Agmon-Levin⁵, Pongthorn Narongroeknawin⁶, Katarzyna Romanowska-Prochnicka⁷, Nan Shen⁸, Hana Ciferská⁹, Masanari Kodera¹⁰, James Cheng-Chung Wei¹¹, Piotr Leszczynski¹², Joung Liang Lan¹³, Rafał Wojciechowski¹⁴, Tunde Tarr¹⁵, Elena Vishneva¹⁶, Yi-Hsing Chen¹⁷, Yuko Kaneko¹⁸, Stephanie Finzel¹⁹, Alberta Hoi²⁰, Masato Okada²¹, Ajchara Koolvisoot²², Shin-Seok Lee²³, Lie Dai²⁴, Hiroshi Kaneko²⁵, Bernadette Rojkovich²⁶, Lingyun Sun²⁷, Eugeny Zotkin²⁸, Jean-François Viallard²⁹, Berta Paula Magallares³⁰, Tirtha Sengupta³¹, Carole Sips³², Carole Lau³³, Alexandre Avrameas³² and Stephen J Oliver³⁴, ¹Organizacion Medica de Investigacion, Buenos Aires, AR, Buenos Aires, Argentina, ²Charité Research Organisation, GmbH, Berlin, DE, Berlin, Germany, ³SM Kirov Military Medical Academy, St Petersburg, RU, St Petersburg, Russia, ⁴Hospital Universitario Vall d´Hebrón Hospitals, Barcelona, ES, Barcelona, Spain, ⁵Center for Autoimmune Disease, Sheba Medical Center, Tel Aviv University, Tel Aviv, IL, Tel Aviv, Israel, ⁶Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, TH, Bankok, Thailand, ⁷Department of Systemic Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PL, Warsaw, Poland, ⁸Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jaiotong University School of Medicine, Shanghai, CN, Shanghai, China (People's Republic), ⁹Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, CZ, Prague, Czech Republic, ¹⁰Department of Dermatology, Japan Community Healthcare Organization, Chukyo Hospital, Nagoya, JP, Nagoya, Japan, ¹¹Department of Rheumatology, Chung Shan Medical University Hospital, Taichung, TW, Taichung, Taiwan (Republic of China), ¹²Department of Internal Medicine, Poznan University of Medicine Sciences, Poznan, PL, Poznan, Poland, ¹³Rheumatology and Immunology Center, China Medical University Hospital, Taichung, TW, Taichung, Taiwan (Republic of China), ¹⁴Department of Rheumatology and Systemic Connective Tissue Diseases, University Hospital No. 2, Bydgoszcz, PL, Bydgoszcz, Poland, ¹⁵Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, HU, Debrecen, Hungary, ¹⁶LLC Family Clinic, Yekaterinburg, RU, Yekaterinburg, Russia, ¹⁷Taichung Veterans General Hospital, Taichung, TW, Taichung, Taiwan (Republic of China), ¹⁸Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JP, Shinjuku-ku, Tokyo, Japan, ¹⁹Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, DE, Freiburg im Breisgau, Germany, ²⁰Monash Health, Monash University, Melbourne, AU, Melbourne, Victoria, Australia, ²¹Immuno-Rheumatology Center, St. Luke’s International Hospital, Tokyo, JP, Tokyo, Japan, ²²Division of Rheumatology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, TH, Bangkok, Thailand, ²³Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, KR, Gwangju, Republic of Korea, ²⁴Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, CN, Guangzhou, China (People's Republic), ²⁵Division of Rheumatic Disease, National Center for Global Health and Medicine, Tokyo, JP, Tokyo, Japan, ²⁶Department of Rheumatology and Physiotherapy, Polyclinic of the Hospitaller Brothers of St. John of God, Semmelweis University, Budapest, HU, Budapest, Hungary, ²⁷Dept of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing Univ Medical School, Nanjing, CN, Nanjing, China (People's Republic), ²⁸V A Nasonova Research Institute of Rheumatology, Moscow, RU, Moscow, Russia, ²⁹CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, FR, Bordeaux, France, ³⁰Dept of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, ES, Barcelona, Spain, ³¹Novartis Pharma India, Hyderabad, IN, Hyderabad, India, ³²Novartis Pharma AG, Basel, CH, Basel, Switzerland, ³³Novartis Pharma, East Hanover, NJ, USA, East Hanover, ³⁴Novartis Pharma AG, Basel, Switzerland

Meeting: ACR Convergence 2024

Keywords: Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 18, 2024

Title: Abstracts: SLE – Treatment II: Non-Cellular Lupus Therapeutics

Session Type: Abstract Session

Session Time: 1:00PM-2:30PM

Background/Purpose: Ianalumab (VAY736) is an afucosylated, fully human IgG1 monoclonal antibody with a dual mechanism of action of enhanced B-cell depletion through antibody-dependent cellular cytotoxicity and B cell–activating factor receptor blockade. Our purpose is to expand upon previously published results from the phase 2 study with longer term (68-week [W]) results from open-label (OL) ianalumab treatment.

Methods: This multi-center, randomized, parallel-group trial included 3 study periods: 1) 28W blinded, placebo-controlled, 2) 24W OL, and 3) post-treatment follow up. We report here 68W results. Patients were randomized (1:1) to either subcutaneous ianalumab 300 mg or placebo every 4 weeks (q4w) and switched at W28 to OL ianalumab through W48. Patients with anti-nuclear antibodies ≥1:80, ≥4 of 11 ACR 1997 SLE classification criteria, SLEDAI-2K score ≥6, and BILAG -2004 ≥1 A or ≥2 B were included. Outcomes were measured at baseline, q4w to W52, and then W60 and W68. The primary W28 outcome was the composite endpoint of patients who achieved both SLE Responder Index (SRI-4) and met corticosteroid (CS) responder criteria (tapering prednisone ≤5 mg/d or ≤baseline dose, whichever was lower, by W16 and kept within that range to W28). W52 composite responders met CS responder criteria from W40 to W52. Other outcomes included SRI-4, SRI-6, SRI-8, incidence BILAG-2004 flares (BILAG-2004 ≥1 A or ≥2 B scores), proportion of patients achieving Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS), safety/tolerability, and laboratory markers for B cell counts and immune activation.

Results: Overall, 67 patients enrolled from December 19, 2018 to January 31, 2022 with median age 42 years and 39 years for ianalumab and placebo arms, respectively. Baseline median (range) values for ianalumab and placebo arms, respectively, were: SLEDAI-2K scores 11 (6-32) and 10 (4-21), and prednisone dose/day 10.0 mg (0-30.0) and 10.0 mg (0-27.5). The proportion of patients treated with ianalumab or placebo achieving composite endpoint criteria for SRI-4 + CS responder at W28 was 44.1% (n/N=15/34) vs 9.1% (n/N=3/33), respectively, and at W52 for patients switching from active treatment to OL ianalumab or switching from placebo to ianalumab was 45.5% (n/N=15/33) vs 40.6% (n/N=13/32; Figure 1). Longer duration of q4w ianalumab exposure at W52 vs W28, or for placebo+24W, resulted in further improvement in outcomes (Table 1) for incidence BILAG flare, status of SRI-6, SRI-8, DORIS and LLDAS, and serum levels of complement and autoantibodies. IgG reduction from baseline (geometric mean, 95% CI) at W52 was 0.78 (0.73-0.84). Treatment responses were maintained during the safety follow up period at W68 without unexpected or new safety findings.

Conclusion: Treatment with ianalumab was well-tolerated, and data suggests longer exposure up to 1 year provides further clinical and laboratory benefits in patients with active SLE. These positive results were maintained up to W68 during the safety follow up. Ianalumab is currently being investigated in large randomized controlled phase 3 studies (NCT05639114; NCT05624749; NCT05126277) in patients with active SLE, and in those with lupus nephritis.

Figure 1. SRI-4 responders over time and composite SRI-4+CS responders (bar graphs)

Table 1. Clinical and laboratory outcomes at weeks 28, 52, and 68

Disclosures: E. Mysler: AbbVie, 2, 5, Alpine Immunology, 2, 5, Amgen, 2, 5, Astra Zeneca, 2, 5, BMS, 2, 5, GSK, 2, 5, HiBio, 2, 5, Janssen, 2, 2, 5, 5, Lilly, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, Roche, 2, 5, Sandoz, 2, 5, Sanofi, 2, 5; S. Ignatenko: None; A. Gordienko: None; J. Cortés-Hernández: None; N. Agmon-Levin: None; P. Narongroeknawin: None; K. Romanowska-Prochnicka: None; N. Shen: None; H. Ciferská: None; M. Kodera: None; J. Cheng-Chung Wei: AbbVie/Abbott, 2, 5, Amgen, 2, AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, 2, 5, Chugai, 2, Eisai, 2, Eli Lilly, 2, 5, Gilead, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Novartis, 2, Pfizer, 2, Sanofi-Aventis, 2, SUN Pharma, 2, TSH Taiwan, 2, UCB pharma, 2; P. Leszczynski: AbbVie/Abbott, 2, AstraZeneca, 2, Merck/MSD, 2, Novartis, 2, UCB, 2; J. Liang Lan: None; R. Wojciechowski: AbbVie/Abbott, 6, Eli Lilly, 6, Novartis, 5, 6, UCB, 6; T. Tarr: None; E. Vishneva: None; Y. Chen: None; Y. Kaneko: None; S. Finzel: AbbVie/Abbott, 2, AstraZeneca, 2, Chugai, 2, Galapagos, 2, Novartis, 2, UCB, 2; A. Hoi: AbbVie/Abbott, 6, AstraZeneca, 5, Australian Rheumatology- Association, 4, 12, Treasurer, Eli Lilly, 6, EUSA Pharma, 2, Limbic, 6, Moose Republic, 6, Novartis, 6; M. Okada: AbbVie, 2, Amgen, 2, Asahi Kasei Pharma, 2, Astellas, 2, AstraZeneca, 2, Ayumi Pharma, 2, Bristol-Myers Squibb(BMS), 2, Chugai, 2, Daiichi Sankyo, 2, Eisai, 2, Eli Lilly, 2, Gilead, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Mitsubishi Tanabe Pharma, 2, Novartis, 2, Ono Pharma, 2, Pfizer, 2, UCB Pharma, 2; A. Koolvisoot: None; S. Lee: None; L. Dai: None; H. Kaneko: None; B. Rojkovich: None; L. Sun: None; E. Zotkin: None; J. Viallard: None; B. Paula Magallares: None; T. Sengupta: Novartis, 3; C. Sips: Novartis, 3; C. Lau: Novartis, 3; A. Avrameas: Novartis, 3; S. J Oliver: Novartis, 3, 11.

To cite this abstract in AMA style:

Mysler E, Ignatenko S, Gordienko A, Cortés-Hernández J, Agmon-Levin N, Narongroeknawin P, Romanowska-Prochnicka K, Shen N, Ciferská H, Kodera M, Cheng-Chung Wei J, Leszczynski P, Liang Lan J, Wojciechowski R, Tarr T, Vishneva E, Chen Y, Kaneko Y, Finzel S, Hoi A, Okada M, Koolvisoot A, Lee S, Dai L, Kaneko H, Rojkovich B, Sun L, Zotkin E, Viallard J, Paula Magallares B, Sengupta T, Sips C, Lau C, Avrameas A, J Oliver S. Safety and Efficacy of Subcutaneous Ianalumab (VAY736) for up to 68 Weeks in Patients with Systemic Lupus Erythematosus: Results from Phase 2 Study [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/safety-and-efficacy-of-subcutaneous-ianalumab-vay736-for-up-to-68-weeks-in-patients-with-systemic-lupus-erythematosus-results-from-phase-2-study/. Accessed .

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