ianalumab (VAY736) / Novartis - LARVOL DELTA

Ianalumab retreatment in adults with primary immune thrombocytopenia (ITP) or warm-antibody autoimmune hemolytic anemia (wAIHA) who benefitted from previous ianalumab treatment: A phase 2 exploratory study (ASH 2025) - P2 | "Corticosteroids (CS) are recommended as first-line treatment in ITP, while second-line recommendations include thrombopoietin receptor agonists (TPO-RAs), rituximab, or splenectomy (Neunert et al. Results : None. Conclusion : Enrollment is ongoing."

Clinical • P2 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment (ASH 2025) - P3 | "Ianalumab in combination with eltrombopag prolonged TTF, improved SR6, reduced fatigue, facilitated tapering off eltrombopag, and delayed need for subsequent therapy in pts with primary ITP previously treated with corticosteroids. Ianalumab was well tolerated, with no observed increase in infection risk relative to placebo. Ianalumab may be disease-modifying when used early in the course of ITP."

Clinical • Late-breaking abstract • P3 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Neutropenia • Thrombocytopenia • Thrombocytopenic Purpura

Secondary analysis results from VAYHIT3, a phase 2 study of ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy (ASH 2025) - P2 | "ConclusionThese secondary analyses support the efficacy profile of ianalumab in heavily pretreated patients withprimary ITP. The treatment demonstrated fast and profound B-cell depletion, as well as consistentbenefits across subgroups, with improvements in bleeding symptoms."

Clinical • P2 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Management of Autoimmune Hemolytic Anemia (ASH 2025) - "For relapsed/refractory patients rituximab has become the preferred second line-therapy, comparing favorably with the traditional splenectomy, which has been progressively abandoned or moved to further lines along with classic immunosuppressors. Several novel treatments are in development for wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

IO biomarker • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • HP • SYK

Ianalumab plus Eltrombopag in Immune Thrombocytopenia. (PubMed, N Engl J Med) - P3 | "Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.)."

Clinical • Journal • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Management of autoimmune hemolytic anemia. (PubMed, Hematology Am Soc Hematol Educ Program) - "Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation • SYK

Novartis ianalumab significantly extends disease control in patients with immune thrombocytopenia with only four once-monthly doses (GlobeNewswire) - "Patients receiving ianalumab (9 mg/kg) plus eltrombopag also achieved a significantly higher rate of sustained platelet count improvement at six months versus placebo plus eltrombopag (62% vs. 39%), meeting the key secondary endpoint. Fatigue improvement, as measured by PROMIS Fatigue, showed a mean reduction of 7.7 points with ianalumab plus eltrombopag versus 3.6 points with placebo plus eltrombopag...Two doses of ianalumab were assessed in VAYHIT2 with ianalumab 9 mg/kg demonstrating statistically significant improvements across both the primary and key secondary endpoints, and ianalumab 3 mg/kg demonstrating statistically significant improvements in the primary endpoint and numerical improvements in the key secondary endpoint....Novartis plans to submit the data from VAYHIT2 along with results from the ongoing first-line ITP trial, VAYHIT1, in 2027."

Filing • P3 data • Immune Thrombocytopenic Purpura

B cell depletion and BAFF receptor blockade with ianalumab (VAY736) for the treatment of moderate-to-severe systemic lupus erythematosus: a phase 2 randomised, double-blind, placebo-controlled trial with subsequent open-label treatment. (PubMed, Ann Rheum Dis) - "At week 28, reduced disease activity was observed in patients with SLE receiving ianalumab plus standard therapies compared with those receiving standard therapies alone, with sustained benefits with further treatment until 1 year, which was well tolerated."

Journal • P2 data • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Phase III Clinical Trial Program Investigating the Efficacy and Safety of Ianalumab in Patients with Primary Immune Thrombocytopenia (VAYHIT1 and VAYHIT2) and Warm Autoimmune Hemolytic Anemia (VAYHIA) (ASH 2023) - P2, P3 | "Ianalumab is a novel, fully human immunoglobulin G1 monoclonal antibody that targets BAFF receptor (BAFF-R) and has a unique dual mechanism of action: direct antibody-dependent cellular cytotoxicity-mediated B-cell depletion and inhibition of B-cell differentiation, proliferation and survival via blockade of BAFF-R-mediated signaling...Thrombopoietin receptor agonists (TPO-RAs), such as eltrombopag, are commonly used second-line ITP treatments and often achieve a response; however, responses are rarely maintained once treatment ends, so chronic administration is typically required. For wAIHA, few treatments have been approved, and patients rarely achieve durable responses on CS or off-label rituximab... These trials have been designed based on the hypothesis that, when administered early in disease progression, medical therapy targeting complementary physiological pathways may restore self-tolerance in patients with ITP and wAIHA. Ianalumab in combination with..."

Clinical • P3 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

VAYHIT3: An Open-Label, Single-Arm, Phase II Trial to Evaluate the Efficacy and Safety of Ianalumab in Patients with Primary Immune Thrombocytopenia (ITP) Previously Treated with at Least 1 Corticosteroid and 1 Thrombopoietin Receptor Agonist (TPO-RA) (ASH 2023) - P2, P3 | "For patients who previously received corticosteroids and a TPO-RA, the choice of subsequent therapy (eg a different TPO-RA, rituximab, fostamatinib, mycophenolate mofetil, splenectomy) is not well defined. VAYHIT3 will evaluate the ability of a short therapeutic course of ianalumab to induce durable responses in patients who have received 2 or more prior lines of therapy, including at least 1 corticosteroid and 1 TPO-RA, for whom significant unmet needs exist. Current status: VAYHIT3 is recruiting. Ianalumab is also being investigated in 2 ongoing, randomized, double-blind, Phase III ITP trials: VAYHIT1 (NCT05653349) is assessing ianalumab versus placebo in addition to first-line corticosteroids, and VAYHIT2 (NCT05653219) is assessing ianalumab versus placebo in addition to eltrombopag in patients who failed first-line corticosteroid treatment."

Clinical • P2 data • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Managed Access Programs for VAY736, Ianalumab (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Novartis Pharmaceuticals

New trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Sjogren's Syndrome • Thrombocytopenia • Thrombocytopenic Purpura

Ianalumab, a Novel Anti-B-Cell Activating Factor (BAFF) Receptor (BAFF-R) Monoclonal Antibody (mAb) in Development for Immune Thrombocytopenia (ITP) and Warm Autoimmune Hemolytic Anemia (wAIHA), Has Demonstrated a Favorable Safety Profile in Sjögren's Syndrome (SjS), Systemic Lupus Erythematosus (SLE) and Chronic Lymphocytic Leukemia (CLL) (ASH 2023) - P1, P2, P3 | "3, 1, 3 or 9 mg/kg every 2 wks plus ibrutinib 420 mg once daily for up to 8 28-day cycles. Ianalumab was safe and well tolerated in patients with SjS. Most AEs were mild or moderate in severity; severe AEs were reported in 5 patients receiving ianalumab. Three ianalumab-treated patients had SAEs; 2 SAEs in 1 patient (appendicitis and tubo-ovarian abscess) were considered related to ianalumab treatment."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Chronic Lymphocytic Leukemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Inflammatory Arthritis • Leukemia • Lupus • Oncology • Renal Disease • Sjogren's Syndrome • Systemic Lupus Erythematosus • Thrombocytopenia • Thrombocytopenic Purpura

Novartis data underscore pioneering scientific innovation in Hematology and Oncology at ASH and SABCS (Novartis Press Release) - "Positive results from ianalumab pivotal Phase III trial in ITP patients previously treated with corticosteroids to be presented as late-breaker."

P3 data • Thrombocytopenia

Human Single Domain Antibody-Based CAR-T Cells Targeting BAFF-R Demonstrate Promising Preclinical Activity in B Cell Malignancies (ASH 2023) - "PMB101 and CAR-T cells constructed with VAY736 were used as positive controls... We developed a novel BAFF-R CAR-T cell product structured on single-domain antibody. This product demonstrated promising preclinical activity, and it may provide an alternative choice for patients with B cell malignancies."

CAR T-Cell Therapy • IO biomarker • Preclinical • Hematological Malignancies • Oncology • LAMP1

A Phase 2 Study of Ianalumab in Patients with Primary Immune Thrombocytopenia Previously Treated with at Least Two Lines of Therapy: Interim Results from VAYHIT3 (ASH 2024) - P2 | "Prior treatments included CS and TPO-RAs (all patients), rituximab (40%), and other immunosuppressants (60%). The IA results on the first 10 patients enrolled in VAYHIT3 suggest that a short course of ianalumab shows promising efficacy and is well tolerated in heavily pretreated patients with ITP. These early interim results support the potential of ianalumab for addressing unmet medical need in primary ITP."

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

Ianalumab, an ADCC-Enhanced Anti-BAFF-Receptor Antibody, Has Beneficial Effects in an Active Mouse Model of Immune Thrombocytopenia (ITP) (ASH 2024) - "Compared with the ITP control, Ianalumab treatment resulted in less thrombocytopenia with an earlier time to recovery, and improved morbidity scores. These findings provide evidence that ianalumab is effective in our murine model of active ITP and represents a strong pre-clinical basis for expecting the drug to be effective in patients with ITP."

Preclinical • Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Primary Immunodeficiency • Thrombocytopenia • Thrombocytopenic Purpura • ITGB3

In a groundbreaking advancement for the treatment of chronic lymphocytic leukemia (CLL), researchers have unveiled promising results from a phase Ib clinical trial assessing the addition of the investigational antibody ianalumab (VAY736) to the established Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib (Imbruvica). (Bioengineer.org) - "Encouragingly, the combination demonstrated a favorable safety profile, with no dose-limiting toxicities reported. While 41% of patients experienced grade 3 or higher adverse effects, these were primarily hematologic, notably neutropenia, which was manageable. The overall response rate neared 60%, underscoring a substantial proportion of patients achieving tumor burden reduction. Importantly, 43.6% attained undetectable MRD (uMRD) in peripheral blood or bone marrow, a key indicator of deep remission that correlates with prolonged progression-free survival."

P1 data • Chronic Lymphocytic Leukemia

Addition of Ianalumab (VAY736) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia on Ibrutinib Therapy: Results from a Phase Ib Study. (PubMed, Clin Cancer Res) - P1 | "Biomarker data suggest that ianalumab increased NK- and T-cell activation. These data support further evaluations of ianalumab in combination with Bruton tyrosine kinase inhibitors for patients with CLL."

Journal • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology

A Phase 2 Study of Ianalumab in Patients With Primary Immune Thrombocytopenia Previously Treated With At Least Two Lines of Therapy (VAYHIT3) (DGHO 2025) - P2 | "Pts had median of 6 prior treatments; all received CS and TPO-RAs, 46% rituximab, and 54% other immunosuppressants. At data cutoff (June 2024), 8 pts (21%) completed wk25, 2 pts discontinued (pt decision; 1 in safety follow-up and 1 left study), and 29 pts were on treatment. Median age was 55 years (range:18–80); 54% were female. Median time from initial ITP diagnosis was 57 months."

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

Novartis ianalumab first drug to reduce disease activity and patient burden in Sjögren’s disease Phase III trials (Novartis Press Release) - "Novartis plans to submit to health authorities globally in early 2026...Numerical improvements were observed as early as Week 16, which were sustained throughout the study. Patients receiving ianalumab showed consistent numerical improvements in secondary outcome measures including: More patients with ESSDAI low disease activity; Improvement in Physician Global Assessment; Reduction in overall disease burden as early as Week 8 continuing to Week 52 as assessed by Patient Global Assessment; Numerical improvement in dryness, pain and fatigue as assessed by Sjögren’s Syndrome Symptom Diary and EULAR Sjögren’s Syndrome Patient Reported Index; Improvement of stimulated Salivary Flow (sSF) rate and oral dryness vs placebo in patients with sSF>0.4 mL/min at baseline, in a post-hoc analysis."

Filing • P3 data • Sjogren's Syndrome

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."

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."

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

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

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

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