ianalumab (VAY736) / Novartis - LARVOL DELTA

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

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

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

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

Phase III Extension Study of Efficacy and Safety of Ianalumab With or Without Study Treatment Withdrawal in Participants With Lupus Nephritis (SIRIUS-LN Extension) (clinicaltrials.gov) - P3 | N=316 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

CDSCO Panel Recommends Protocol Amendment For Novartis' Ianalumab trial (Medical Dialogues) - "The Subject Expert Committee (SEC) on Haematology, functional under the Central Drugs Standard Control Organisation (CDSCO) has recommended for approval of a protocol amendment in an ongoing global clinical trial of Ianalumab (VAY736) by Novartis Healthcare Private Limited....The matter was taken up during the 4th SEC (Haematology) meeting of 2025 held on April 8 at CDSCO headquarters, New Delhi....According to the official minutes, 'The firm presented protocol amendment version 05 dated 27 January 2025 protocol no. CVAY736I12301. After detailed deliberation, the committee recommended for approval of protocol amendment as presented by the firm.'"

Clinical protocol • Thrombocytopenia

CXCR5 as a Therapeutic Target in Autoimmune Diseases: Insights from Sjögren'sSyndrome (CIS 2025) - "Notably, HFB100204 selectively depletes CXCR5+ B cells more potently than rituximab and ianalumab from human PBMCs. This study underscores the therapeutic potential of targeting the CXCR5/CXCL13 axis for I&I. Using SS as an example, we show that at a single-cell level, CXCR5 is critical for the disease progression. HFB100204 effectively depletes pathogenic CXCR5+ immune cells, including B cells and Tfh cells, offering a novel strategy for autoimmune diseases."

Immunology • Inflammation • Inflammatory Arthritis • Sjogren's Syndrome • CXCL13 • CXCR5

New Novartis data at ASCO and EHA showcase momentum of pioneering portfolio with promising pipeline (Novartis Press Release) - "Fabhalta APPULSE-PNH full results build on Phase III program, reporting new data from expanded PNH population in adults switching from anti-C5; Ianalumab Phase II data in immune thrombocytopenia..."

Clinical data • Paroxysmal Nocturnal Hemoglobinuria • Thrombocytopenia

Phase 3 Study to Evaluate Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1) (clinicaltrials.gov) - P3 | N=406 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jan 2027 ➔ Apr 2027

Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CTLA4 • IFNAR2

Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=18 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; Business decision and not due to any safety or tolerability concerns.

Trial termination • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CDSCO Panel Approves Novartis Protocol Amendment Proposal Fo Ianalumab Study (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved the protocol amendment proposal presented by Novartis for the clinical trial...This came after the firm presented protocol amendment version 05 dated 22 Aug 2024, protocol no. CVAY736O12301....At the recent SEC meeting for Hematology held on 6th March 2025, the expert panel reviewed the protocol amendment version 05 dated 22 Aug 2024, protocol no. CVAY736O12301. After detailed deliberation, the committee recommended approval of the protocol amendment as presented by the firm."

Clinical protocol • Anemia

VAYHIT2: A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids (clinicaltrials.gov) - P3 | N=152 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

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

Biopsy Based Study to Understand Mechanism of Action of Ianalumab in Salivary Glands and Explore Relationships With Clinical Assessments. (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jun 2026 ➔ Jun 2024

Trial primary completion date • Immunology • Sjogren's Syndrome

Novartis’ Ianalumab granted FDA orphan designation (Markets Insider) - "Novartis...Ianalumab, for the treatment of primary immune thrombocytopenia, was granted FDA orphan designation, according to a post on the agency’s website."

Orphan drug • Thrombocytopenia

VAYHIT3: A Study of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least Two Lines of Therapies (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Mar 2027 ➔ Feb 2025

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