ianalumab (VAY736) / Novartis - LARVOL DELTA

The Sjögren's Tool for Assessing Response (STAR) demonstrates its ability to accurately detect treatment efficacy in 11 recent RCTs in Sjögren's disease (ACR Convergence 2025) - P2, P3 | "We conduscted this study to evaluate the performance of STAR in previously completed clinical trials shared within the NECESSITY consortium. Data from 9 trials used for STAR development (Abatacept (ASAP-III), leflunomide+hydroxychloroquine (REPURP-SS) and rituximab (TEARS and TRACTISS), the iscalimab and ianalumab phase 2 trials, Baminercept, hydroxychloroquine (JOQUER), tocilizumab (ETAP)) and two other independent clinical trials (GSK (NCT02631538), Belimumab + Rituximab, Belimumab, Rituximab versus placebo and BMS Abatacept (NCT02915159). In this analysis based on 11 trials, the STAR appears to detect treatment response accurately, with a high sensitivity to change for treatments showing a beneficial effect. Additionally, it exhibits specificity to change by not falsely detecting improvement in negative trials."

Clinical • Sjogren's Syndrome

Evaluation of the Ianalumab Treatment Effects on Major Salivary Glands of Patients With Sjögren's Disease by Multimodal Ultrasound: Results From a Phase 2 Mechanistic Study (ACR Convergence 2025) - P2 | "Patients treated with ianalumab 300 mg monthly showed improvement in PGs structure and vascularization at W25 vs BL using multimodal ultrasound assessment. Innovative measures with CEUS display a good sensitivity to change after treatment and should be considered in future clinical trials. Reference 1."

Clinical • P2 data • Immunology • Sjogren's Syndrome

Evaluation of the Dual Mode of Action of Ianalumab (VAY736) in the Circulation and Salivary Gland Tissue of Patients With Sjögren's Disease: Results From a Phase 2 Mechanistic Study (ACR Convergence 2025) - P2 | "Ianalumab 300 mg monthly treatment almost completely depleted B cells in the circulation, and to a large extent in labial SG tissue, in line with improvement in clinical and serological parameters at W25 vs BL. These observations suggest direct and relevant effects of ianalumab 300 mg monthly on the target tissue in patients with SjD. Additionally, ianalumab 300 mg monthly modified the phenotype of the remaining B cells in circulation, shedding new light on the dual mechanism of action of ianalumab."

Clinical • P2 data • Immunology • Sjogren's Syndrome

Preexisting Antibodies Against Vaccine Antigens Are Preserved In Patients With Systemic Lupus Erythematosus and Sjögren's Disease Upon Ianalumab Treatment While Autoantibodies Decline (ACR Convergence 2025) - P2 | "Treatment with ianalumab up to 52 weeks did not result in a reduction of the Ab titers to previous immunizations against tetanus, varicella, measles, mumps, rubella, diphtheria, and influenza while having a clear impact on auto-Ab levels. References McWilliams EM, et al. Blood Adv 2019; 3(3):447-460."

Clinical • Immunology • Infectious Disease • Inflammatory Arthritis • Influenza • Lupus • Measles • Mumps • Respiratory Diseases • Rubella • Sjogren's Syndrome • Systemic Lupus Erythematosus • Tetanus • Varicella Zoster

Achieving Sustained Lupus Low Disease Activity State and Remission with Ianalumab (VAY736) in Patients with Systemic Lupus Erythematosus: A Post Hoc Analysis from a Phase II Study (ACR Convergence 2025) - P2 | "A 52W week of ianalumab treatment was associated with more time in LLDAS and DORIS, as well as higher attainment of GC taper goals compared to 28W placebo followed by 24W ianalumab exposure. This suggests that earlier ianalumab exposure led to cumulative clinical benefit in patients with SLE. Larger studies are required to confirm these findings."

Clinical • P2 data • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Ianalumab's dual mode of action: targeting B cells through enhanced B cell depletion and blockade of B cell-activating factor receptor signaling (ACR Convergence 2025) - P2 | "The efficacy of B cell depletion following administration of ianalumab in C57/B6 and NOD mice was investigated using flow cytometry and/or histology in blood and relevant organs. In an ADCC assay co-culturing purified NK cells with B cells from HVs, ianalumab showed a 44-fold increased potency compared to rituximab (Fig. Ianalumab, through its dual mechanism of action, addresses limitations of first-generation B cell targeting therapies for auto-immune diseases by providing more potent B cell depletion and additional BAFF-R blockade on remaining B cells. Accordingly, patients with SLE (NCT03656562) or SjD (NCT02962895) treated with ianalumab for up to 52 weeks showed sustained reduction in disease activity in phase 2 trials [2,3]. Ongoing phase 3 studies in SjD, SLE and LN will provide further evidence on the efficacy and safety of ianalumab in larger patient populations.References: 1."

Immunology • Inflammatory Arthritis • Obesity • Sjogren's Syndrome • NFKB2

Clinical Outcomes and Response to SARS-Cov-2 Infection and Vaccination in Ianalumab‑Treated Patients with Autoimmune Diseases (ACR Convergence 2025) - P1, P2 | "This analysis suggests that ianalumab treatment did not seem to increase the risk of severe SARS-CoV-2 infection in patients with SjD, RA or SLE. Both ianalumab and placebo groups mounted a serological response to SARS-CoV-2 vaccine, which improved during the follow-up even before B-cell recovery. Limitations include small sample size, imbalance in the patient number and observation time, varying risks, geographical regions, SARS-CoV-2 variants and vaccine availability.References: World Health Organization."

Clinical • Clinical data • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Respiratory Diseases • Sjogren's Syndrome

VAYHIT1: Study of Ianalumab Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P3 | N=226 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (clinicaltrials.gov) - P2 | N=107 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ Apr 2025

Trial completion • Trial completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Novartis announces both ianalumab Phase III clinical trials met primary endpoint in patients with Sjögren’s disease (Novartis Press Release) - "Both trials met the primary endpoint of demonstrating statistically significant improvements in disease activity...The NEPTUNUS pivotal trials achieved the primary endpoint of improving disease activity measured by a reduction in EULAR Sjögren’s syndrome disease activity index (ESSDAI), a multi-dimensional disease activity measurement compared to placebo. Ianalumab was well tolerated and demonstrated a favorable safety profile in Sjögren's disease....Novartis plans to present the NEPTUNUS-1 and NEPTUNUS-2 data at an upcoming medical meeting and submit ianalumab, which was granted Fast Track Designation by the US Food and Drug Administration (FDA), to health authorities globally."

P3 data: top line • Sjogren's Syndrome

Ianalumab: Data from P3 SIRIUS-SLE 1 trial (NCT05639114) for SLE in 2027 (Novartis) - Q2 2025 Results: Data from P3 SIRIUS-SLE 2 trial (NCT05624749) for SLE in 2027

P3 data • Lupus • Lupus Nephritis

A Phase 2 Study of Ianalumab in Patients With Primary Immune Thrombocytopenia Previously Treated With at Least Two Lines of Therapy (VAYHIT3) (SOHO 2025) - P2 | "All patients received prior corticosteroids and TPO-RAs, 46% prior rituximab, and 54% other immunosuppressants. Interim analysis provided first data on patients with primary ITP treated with ianalumab, showing preliminary efficacy and safety over a short course. The primary analysis results from all 41 patients (data cutoff February 2025) will be presented."

Clinical • P2 data • Oncology

Results from ongoing trials and other highlights (Novartis Press Release) - P2 | N=248 | NCT03827798 | Sponsor: Novartis Pharmaceuticals | "Novartis will not advance investigation of ianalumab in hidradenitis suppurativa following a Phase II proof-of-concept study which did not meet our target criteria despite demonstrating efficacy vs placebo. No new safety signals were observed and all other studies for ianalumab in B-cell driven diseases continue as planned."

Discontinued • P2 data • Hidradenitis Suppurativa

SIRIUS-SLE LTE: Phase 3 Extension Study to Evaluate Long-term Safety of Ianalumab in Participants With Systemic Lupus Erythematosus (SIRIUS-SLE Extension). (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2031 ➔ Apr 2032 | Trial primary completion date: Dec 2029 ➔ Apr 2030

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Ianalumab: Primary data from P3 SIRIUS-LN trial (NCT05126277) for lupus nephritis in 2027 (Novartis) - Q2 2025 Results

P3 data • Lupus • Lupus Nephritis

SIRIUS-LN: Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jul 2030 ➔ Nov 2030 | Trial primary completion date: Mar 2027 ➔ Jun 2027

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

NEPTUNUS-Ext: A Randomized, Double-blind 2-arm NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome. (clinicaltrials.gov) - P3 | N=613 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Sjogren's Syndrome

A PHASE 2 STUDY OF IANALUMAB IN PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA PREVIOUSLY TREATED WITH AT LEAST TWO LINES OF THERAPY (VAYHIT3) (EHA 2025) - P2 | "Pts were heavily pretreated, with a median number of 6 prior treatment lines; all pts received prior CS and TPO-RAs, 46% prior rituximab, and 54% other immunosuppressants.Five (50%) out of the 10 pts included in the interim efficacy analysis achieved ConfR. The interim analysis results are the first data on pts with primary ITP treated with ianalumab, providing preliminary efficacy and safety data over a short treatment course. The primary analysis results from all 41 pts with longer follow-up (data cutoff Feb 2025) will be presented at EHA 2025."

Clinical • P2 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

IANALUMAB' S DUAL MECHANISM OF ACTION: TARGETING B CELLS THROUGH ENHANCED B-CELL DEPLETION AND BLOCKADE OF B CELL-ACTIVATING FACTOR RECEPTOR SIGNALING (EHA 2025) - P2, P3 | "Ianalumab, through its dual mechanism of action, provides more potent B-cell depletion than rituximab and additional BAFF-R blockade on remaining B cells in vitro and demonstrates reduced disease activity in a murine ITP model. Data from an interim analysis of the first 10 patients enrolled in a Phase 2 study of ianalumab in patients with primary ITP previously treated with at least 2 lines of therapy (NCT05885555) have provided preliminary efficacy (at 25 weeks) and safety information.3 Phase 3 studies are ongoing to investigate the efficacy and safety of ianalumab in 1L and 2L primary ITP (NCT05653349 and NCT05653219, respectively) as well as warm autoimmune hemolytic anemia (NCT05648968)."

Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • NFKB2

VAY RE-HIT: Exploratory Study of Ianalumab in Adults With Primary Immune Thrombocytopenia (ITP) and Warm-antibody Autoimmune Hemolytic Anemia (wAIHA) Who Have Previously Benefited From Ianalumab (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

EFFICACY OF IANALUMAB IN A MOUSE MODEL OF AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA) (EHA 2025) - "These data suggest that ianalumab may be effective in reducing anti-RBC autoantibodies in wAIHA. The observed restoration of Teff/Treg balance by ianalumab also highlights its immunomodulatory potential in inducing durable responses."

Preclinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • CD21 • FOXP3

Ianalumab's dual mode of action: targeting B cells through enhanced B cell depletion and blockade of B cell-activating factor receptor signaling (EULAR 2025) - P2 | "In an ADCC assay co-culturing purified NK cells with B cells from HVs, ianalumab showed a 44-fold increased potency compared to rituximab (Figure 1A). Ianalumab, through its dual mechanism of action, addresses limitations of first-generation B cell targeting therapies for auto-immune diseases by providing more potent B cell depletion and additional BAFF-R blockade on remaining B cells. Accordingly, patients with SjD (NCT02962895) or SLE (NCT03656562) treated with ianalumab for up to 52 weeks showed sustained reduction in disease activity in phase 2 trials [2, 3]. Ongoing phase 3 studies in SjD, SLE and LN will provide further evidence on the efficacy and safety of ianalumab in larger patient populations."

Immunology • Inflammatory Arthritis • Lupus • Obesity • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • NFKB2

Clinical trial participation in Sjogren's disease (EULAR 2025) - "The Dazodalibep and Ianalumab trials increased their eligibility by 11.97% and 147.06%, respectively, by utilising a double-cohort design which allowed for the participation of a second cohort of “low-ESSDAI, high-ESSPRI” patients. In this exciting era of SjD trials, an increased understanding of the benefits and limitations of trial design is vital to ensure that both clinicians and SjD patients, including those with vulnerable characteristics, have adequate treatment decision information. Our data highlight the clinical heterogeneity of the real-world SjD population, the differing impact of particular inclusion criteria, and the benefit of the double-cohort design in increasing patient inclusion."

Clinical • Dry Eye Disease • Infectious Disease • Ophthalmology • Respiratory Diseases • Sjogren's Syndrome • Tuberculosis

Clinical outcomes and response to SARS-CoV-2 infection and vaccination in ianalumab-treated patients with autoimmune diseases (EULAR 2025) - P1, P2 | "The findings from this retrospective analysis suggest that ianalumab treatment did not seem to increase the risk of severe SARS-CoV-2 infection in patients with SjD, RA or SLE. Furthermore, patients from both ianalumab and placebo groups mounted a serological response to SARS-CoV-2 vaccine, for which the extent was modulated by when the vaccination occurred during treatment, increasing during follow-up even before B cell recovery. Limitations of this retrospective study include small sample size, imbalance in the number and observation time for patients in the ianalumab and placebo groups, variations in the risk of infection over time, geographical regions, SARS-CoV-2 variants and vaccine availability."

Clinical • Clinical data • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus

Preexisting antibodies against vaccine antigens are preserved in patients with systemic lupus erythematosus and Sjögren's disease upon ianalumab treatment while autoantibodies decline (EULAR 2025) - P2 | "Treatment with ianalumab up to 52 weeks did not result in a reduction of the antibody titers to previous immunizations against tetanus, varicella, measles, mumps, rubella, diphtheria and influenza while having a clear impact on autoantibody levels."

Clinical • Immunology • Infectious Disease • Inflammatory Arthritis • Influenza • Lupus • Measles • Mumps • Respiratory Diseases • Rubella • Sjogren's Syndrome • Systemic Lupus Erythematosus • Tetanus • Varicella Zoster