ianalumab (VAY736) / Novartis - LARVOL DELTA

Patient Global Assessment Correlates With the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and the Sjögren's Syndrome Symptom Diary (SSSD) in the Pooled Phase 3 NEPTUNUS Studies (ACR Convergence 2026) - P3 | "Ianalumab is a fully human IgG1 monoclonal antibody with a novel dual mechanism of action that depletes B cells through enhanced antibody-dependent cellular cytotoxicity and inhibits their activation and survival via B-cell activating factor receptor blockade... In this analysis, PaGA showed consistent correlations with both ESSPRI and SSSD, providing a clinically meaningful framework for interpreting PaGA in relation to established symptom-based PROs in SjD. At the same time, the moderate strength of these correlations suggests that PaGA is not fully explained by existing symptom-focused PROs and may capture additional dimensions of the patient experience. Further research is needed to better understand the constructs underlying PaGA and to inform the continued evolution of the PRO framework in SjD."

Clinical • P3 data • Immunology • Sjogren's Syndrome • Xerostomia

Ianalumab reduces disease activity across ESSDAI domains: Post hoc analysis from the pooled Phase-3 NEPTUNUS-1 and NEPTUNUS-2 trials in Sjögren's disease (ACR Convergence 2026) - "Shift analysis indicated that half of ianalumab-patients treated with moderate-high activity at baseline moved to low-no disease activity by Wk24, with further improvements observed by Wk48. Across several individual domains with moderate to high activity at baseline, a higher proportion of patients treated with ianalumab QM shifted to no activity and reported fewer active domains at Wk48 vs placebo. These data further support the clinical relevance of ianalumab in the treatment of SjD, reinforcing and extending the observed group-level reductions in ESSDAI disease activity."

P3 data • Retrospective data • Sjogren's Syndrome

Efficacy and Safety of B-Cell Targeted Monoclonal Antibodies in Primary Sjögren's Syndrome: A Systematic Review and Meta-analysis (ACR Convergence 2026) - " Following PRISMA 2020, PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched through January 2026 for RCTs comparing B-cell targeted monoclonal antibodies, including rituximab, belimumab, iscalimab, and ianalumab, with placebo in Sjögren's disease. In randomized trials of Sjögren's disease, monoclonal antibodies did not show a consistent class-wide benefit across systemic disease activity, salivary function, or sustained fatigue. However, reproducible ESSPRI improvement with iscalimab and early fatigue benefit with ianalumab suggest that efficacy may be target-dependent. Serious adverse events and serious infections were not significantly increased, although agent-specific tolerability signals warrant further evaluation."

Retrospective data • Review • Immunology • Infectious Disease • Sjogren's Syndrome

Efficacy and Safety of Targeted Immunomodulatory Monoclonal Antibodies in Primary Sjögren's Syndrome: A Systematic Review and Meta-analysis (ACR Convergence 2026) - " Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through January 2026 for RCTs comparing mAbs including rituximab, belimumab, tocilizumab, iscalimab, nipocalimab, and ianalumab against placebo with subgroup analysis according to the mechanism of action. Monoclonal antibodies were associated with modest but significant improvements in systemic disease activity and patient-reported outcomes in primary Sjögren's syndrome, with limited benefit for glandular function. CD40-CD40L blockade showed the most consistent ESSDAI improvement, although subgroup sample sizes were small. Overall safety was acceptable, but agent-specific adverse event signals, particularly with ianalumab, warrant careful patient selection and monitoring."

Immunomodulating • Retrospective data • Review • Immunology • Sjogren's Syndrome • CD40LG

Evaluation of the Ianalumab Treatment Effects on Parotid and Submandibular Glands of Patients with Sjögren's Disease by Multimodal Ultrasound: Results from a Phase 2 Mechanistic Study (ACR Convergence 2026) - P2 | "Ianalumab Tx showed a global reduction in SjD-related inflammation of major SGs as assessed by OMERACT scores. These changes paralleled improvements in clinical endpoints related to SG function and illustrate SGUS as a valuable method of assessing SjD disease activity in clinical studies."

Clinical • P2 data • Inflammation • Sjogren's Syndrome

BILAG 2004 Low Disease Activity States as Alternative Endpoints to SRI 4 and BICLA in SLE (ACR Convergence 2026) - P2 | " Post‑hoc analysis compared BICLA and SRI‑4 with BILAG‑2004 LDA states using data from the ianalumab cohort of a Phase 2 randomized, double‑blind, placebo‑controlled trial (NCT03656562) with subsequent open‑label treatment in patients with moderate‑to‑severe systemic lupus erythematosus (SLE)... In this exploratory analysis, BILAG‑2004 LDA and BST Persistent LDA showed similar ability to characterize treatment response compared with SRI‑4 and BICLA. These findings suggest that BILAG‑2004‑based LDA states may warrant further evaluation in additional studies to assess robustness and generalizability across different trial settings. SRI-4 and BICLA responder rates during double-blind treatment period BILAG-2004 LDA and BST Persistent LDA responder rates during double-blind treatment period"

Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

How Does the Physician's Global Assessment Contribute to SRI-4 and BICLA? (ACR Convergence 2026) - P2 | "This analysis explored the extent to which PhGA contributes to the ability of SRI‑4 and BICLA to detect the treatment effect of ianalumab... In this adjudicated study, PhGA appeared redundant within these composite endpoints. Reducing complexity of composite endpoints may improve trial efficiency and reduce site burden without compromising endpoint performance. While these findings support further exploration of simplified composite definitions, confirmation across additional datasets would be required."

Clinical • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety profile of ianalumab in Sjögren's disease: Observations from the pooled results of the phase 3 trials NEPTUNUS-1 and NEPTUNUS-2 up to 52 weeks. (ACR Convergence 2026) - "The cumulative safety data for ianalumab demonstrated that ianalumab QM is generally well-tolerated and has a favorable safety profile in patients with moderate to severe SjD. References Mariette X, Criswell LA. NEJM."

Clinical • P3 data • Breast Cancer • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Sjogren's Syndrome • Solid Tumor • Waldenstrom Macroglobulinemia

Long Term Changes in B cell Subsets in Systemic Lupus Erythematosus Following Ianalumab Treatment: Exploratory Analysis of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study (ACR Convergence 2026) - P2 | "This analysis confirms an altered BCR repertoire in SLE, consistent with extrafollicular maturation. Ianalumab 300 mg s.c. QM treatment induced broad and deep B cell depletion across B cell subsets, followed by a shift towards a re-equilibration of the B cell repertoire and sustained autoantibody reduction during B cell reconstitution, suggesting prolonged effects on B cell homeostasis. These findings are consistent with ianalumab's dual mechanism of B cell depletion and BAFF-R blockade."

Clinical • IO biomarker • P2 data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety and Efficacy of Subcutaneous Ianalumab (VAY736) Post-B Cell Recovery in Patients with Systemic Lupus Erythematosus: End-of-Study Results from a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study (ACR Convergence 2026) - P2 | "Alongside improved responses with ianalumab vs placebo at W28, that were maintained or further increased on OL treatment, patients with longer ianalumab exposure (300 mg Q4W up to W52) showed more durable benefits post-treatment and having achieved B cell recovery. These results need further confirmation from larger trials."

Clinical • P2 data • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Neutropenia • Systemic Lupus Erythematosus

Evidence of the Dual Mechanism of Action of Ianalumab in the Circulation and Salivary Gland Tissue of Patients with Sjögren's Disease: Results from a Phase 2 Mechanistic Study (ACR Convergence 2026) - P2 | "Ianalumab Tx reduced B cells in circulation and labial SG tissue, and modified the phenotype of the remaining/emerging B cells in correlation with improvement in Schirmer's test and stimulated salivary flow rate. These data highlight the relevance of the dual MoA of ianalumab, particularly BAFF-R blockade, to B cell infiltration and organization in SG tissue."

Clinical • P2 data • Sjogren's Syndrome • CD20 • CXCR5 • IFNG

The Sjögren's Tool for Assessing Response (STAR) demonstrates its ability to accurately detect treatment efficacy in 17 recent RCTs in Sjögren's disease (ACR Convergence 2026) - P1/2, P2, P2/3, P3 | " The following data were used to assess the performance of 20 STAR candidate options: Data from 9 clinical trials used for STAR development: abatacept (NCT02915159), leflunomide + hydroxychloroquine (REPURPSS-I, EudraCT 2020-001933-11), rituximab (TEARS NCT0074094, TRACTISS ISRCTN65360827), hydroxychloroquine (JOQUER NCT00632866), tocilizumab (NCT01782235), baminercept (NCT01552681), and phase II trials of iscalimab (NCT02291029) and ianalumab (NCT02962895). Data from 7 independent clinical trial datasets (external validation set): belimumab ± rituximab (NCT02631538), abatacept (NCT02915159), anti-IL-7 therapy (NCT04605978), remibrutinib (NCT04035668), iscalimab (NCT03905525, cohorts 1 and 2), leflunomide + hydroxychloroquine (EudraCT 2020-001933-11), and dazodalibep (NCT04129164)... This large number of new trials provided a large amount of data for informing the selection of the final STAR responder index. The STAR 3AV1 where response rely on..."

Clinical • Sjogren's Syndrome • IL7

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: Apr 2032 ➔ Oct 2034 | Trial primary completion date: Apr 2030 ➔ Apr 2034

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

Epidermolysis bullosa acquisita induced by ianalumab used in the treatment of autoimmune haemolytic anaemia: a paradoxical immunological phenomenon (EADV 2026) - "Her history was significant for warm autoimmune haemolytic anaemia (AIHA) which had relapsed despite rituximab...She received treatment with intravenous immunoglobulin 2 g/kg in combination with mycophenolate mofetil 1.5 g twice daily and prednisolone 35 mg daily...It is also possible that a chronic state of severe B-cell depletion induced by ianalumab creates an immunological landscape that favours the pathogenesis of EBA through various mechanisms involving the modification of T helper cell response and cytokine signalling. Our findings highlight the complex interplay between B-cell and T-cell dynamics in autoimmune pathogenesis."

Anemia • Autoimmune Hemolytic Anemia • Bullous Pemphigoid • Dermatopathology • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Ophthalmic Treatments and Evolving Management of Sjögren's Disease: An Overview. (PubMed, J Clin Med) - "Additionally, emerging therapeutics are shifting care from palliative lubrication to targeted secretomotor and biological reactivation, including cold thermosensory TRPM8 agonists (acoltremon 0.003%), water-free formulations (0.1% cyclosporine, perfluorohexyloctane), reactive aldehyde species (RASP) modulators (reproxalap), syndecan-1 receptor agonists (Lacripep), systemic B-cell depleting biotherapy (ianalumab), trigeminal neurostimulation, and combined intense pulsed light with meibomian gland expression (IPL + MGX). Ophthalmic SjD management has evolved from palliative lubrication toward a stepwise, mechanism-directed paradigm integrating novel diagnostics, secretomotor stimulation, mechanical protection, and biologic disease modification; dedicated SjD-specific trials remain essential to validate these emerging interventions."

Journal • Review • Conjunctivitis • Dry Eye Disease • Inflammation • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • MMP9 • SDC1 • TRPM8

VAY2EXPLORE: A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P2 | N=164 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: May 2028 ➔ Jan 2029

Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Immunosuppressive and immunomodulatory therapies in Sjögren's disease: current landscape and future perspectives. (PubMed, Expert Opin Pharmacother) - "CAR-T cell therapy application in refractory SjD patients currently represents an emerging, strictly experimental approach requiring rigorous evaluation of safety and long-term feasibility. Ultimately, identifying the most effective therapeutic agents will likely require discovering and implementing biomarkers tailored to specific biological endotypes."

IO biomarker • Journal • Review • Immunology • Sjogren's Syndrome • CD40LG • CTLA4

Effects of Ianalumab Treatment on B-Cell Activation, Maturation, and Maintenance of Vaccine Titers in Patients With Primary Immune Thrombocytopenia in the Phase 2 VAYHIT3 Study (SOHO 2026) - P2 | "A short ianalumab course led to rapid, profound, sustained depletion of all B-cell subsets, with an increase in sBAFF indicating potent BAFF-R blockade and a decrease in sBCMA suggesting a reduction in plasmablasts and plasma cells, thus supporting ianalumab's novel dual mechanism. Additionally, T- and NK-cell populations and preexisting vaccine-specific immune responses were retained. BAFF-R: B cell–activating factor receptor, EOT: end of therapy, ITP: immune thrombocytopenia, IVIG: intravenous immunoglobulin, NK cell: natural killer cell, sBAFF: soluble B cell–activating factor, sBCMA: soluble B-cell maturation antigen This abstract was previously submitted to EHA 2026."

Clinical • P2 data • Oncology • CD4 • CD8

A Phase 2 Open-Label Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's-Choice Thrombopoietin Receptor Agonist in Patients With Primary Immune Thrombocytopenia: VAY2EXPLORE Study Design (SOHO 2026) - P2, P3 | " The phase 2 multicenter, open-label study (VAY2EXPLORE; NCT07421167) will enroll approximately 149 patients with primary ITP, with 25–60 patients each on IC eltrombopag, avatrombopag, or romiplostim per approved prescribing information for ≤6 months. The VAY2EXPLORE study will expand upon previous findings and assess the tolerability and benefit of ianalumab with IC TPO-RAs in patients with ITP. Funding: This study was funded by Novartis Pharmaceuticals Corporation."

Clinical • P2 data • Oncology

Effect of Ianalumab Plus Eltrombopag on Patient-Reported Outcomes in Primary Immune Thrombocytopenia: Results From the VAYHIT2 Phase 3 Trial (SOHO 2026) - P3 | "ITP-specific PROs improved across symptoms, fatigue, bother, and activity domains in all groups, with greater and more consistent improvements with ianalumab 9 mg/kg. No indication of increased treatment-related bother was observed with the addition of ianalumab. This abstract was previously submitted to EHA 2026."

Clinical • P3 data • Patient reported outcomes • Oncology

Bridging the Gap in Sjögren's Disease: A Comprehensive Review of Unmet Needs, Diagnostic Challenges, and Emerging Therapeutic Strategies. (PubMed, Cureus) - "No disease-modifying therapy is currently approved for SjD, and management remains largely symptomatic, centered on artificial tears, sialogogues, and hydroxychloroquine, none of which reliably arrest systemic immunopathology. Finally, emerging therapeutic strategies are highlighted, including B-cell/BAFF-receptor-targeted ianalumab, the FcRn blocker nipocalimab, and the CD40-CD40L pathway inhibitor dazodalibep, which have demonstrated promising efficacy signals in randomized controlled trials. Improving outcomes in SjD will require earlier recognition, more consistent application of validated outcome measures in routine practice, and rational adoption of emerging immunoselective therapies guided by biomarker-based patient stratification."

IO biomarker • Journal • Review • Cognitive Disorders • Fatigue • Hematological Malignancies • Immunology • Lymphoma • Oncology • Pain • Rheumatology • Sjogren's Syndrome • CD40LG

SIRIUS-LN: Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis (clinicaltrials.gov) - P3 | N=452 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jun 2027 ➔ Sep 2027

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

From Molecular Pathophysiology to Clinical Trial Design in Sjögren's Disease: A Three-Axis Framework. (PubMed, Int J Mol Sci) - "Recent positive trials-phase III for ianalumab in NEPTUNUS-1/2, phase 2b for iscalimab in TWINSS, phase 2 for nipocalimab in DAHLIAS, and phase 2 for dazodalibep in a phenotype-defined symptom-dominant cohort-illustrate that meaningful clinical benefit becomes detectable once stratification is aligned to biology. By integrating molecular endotypes, validated biomarkers, composite endpoints, and phenotype-matched therapies onto a single explicit architecture, SjD shifts from a recurring example of translational failure to a model for precision medicine in heterogeneous autoimmune disease. The central message is that SjD may be less intrinsically treatment-resistant than it has historically been treatment-mistargeted."

Biomarker • Journal • Review • Immunology • Rheumatology • Sjogren's Syndrome

Kinetics of platelet response with ianalumab plus eltrombopag vs eltrombopag alone in patients with primary immune thrombocytopenia (ITP) treated in the second-line setting in the randomized, double-blind, phase 3 VAYHIT2 study (ISTH 2026) - P3 | "doi: 10.1056/NEJMoa2515168. Table or Figure Upload (1) DOI*10.1016/j.rpth.2026.103588"

Clinical • P3 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Ianalumab: Data from P3 VAYHIT1 trial (NCT05653349) for 1L immune thrombocytopenia in H2 2026 (Novartis) - Q2 2026 Results

P3 data • Immune Thrombocytopenic Purpura • Immunology