iscalimab (CFZ533) / Novartis, Xoma - LARVOL DELTA

Targeted immunotherapies for Graves' thyroidal & orbital diseases. (PubMed, Front Immunol) - "They include rituximab, an anti-CD20 monoclonal antibody which causes rapid B cell depletion; ATX-GD-59, an antigen specific immunotherapy which restores immune tolerance to thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 co-stimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor blocking monoclonal antibody...Both tocilizumab (anti-interleukin 6 receptor monoclonal antibody) and sirolimus (mammalian target of rapamycin inhibitor) showed promise in glucocorticoid resistant active disease. Teprotumumab, an anti-insulin-like growth factor-1 receptor monoclonal antibody, demonstrated remarkable all-round efficacy across a wide disease spectrum. Linsitinib, a dual small molecule inhibitor of insulin-like growth factor-1 receptor and insulin receptor, displayed significant proptosis reduction in its phase 2b/3 study. Finally, Batoclimab, an anti-neonatal fragment crystallizable receptor monoclonal antibody,..."

Journal • Review • Endocrine Disorders • Grave’s Disease • Immunology • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Thyroid Eye Disease • CD40LG • IL6R • IR

Iscalimab in Adolescents and Young Adults with New-Onset Type 1 Diabetes (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Costimulation blockade: the next generation. (PubMed, Curr Opin Organ Transplant) - "The focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients."

Journal • Cardiovascular • Transplantation • CD40LG

Infections in Sjögren's disease: a clinical concern or not? (PubMed, Clin Exp Rheumatol) - "While biologic therapies, including predominantly rituximab and belimumab have become increasingly utilised, they carry inherent risks of infections due to their immunosuppressive effects. Emerging therapies, such as ianalumab, iscalimab, dazodalibep, and remibrutinib, show efficacy in reducing disease activity but also present infection risks, with reports of upper respiratory infections and serious cases, including pneumonia and COVID-19. By exploring these infection-related challenges, this review underscores the importance of understanding the infection-autoimmunity relationship to improve outcomes for patients with SjD and similar autoimmune conditions."

Journal • Review • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Sjogren's Syndrome • Urology

New Developments and Therapeutic Drug Monitoring Options in Costimulatory Blockade in Solid Organ Transplantation: A Systematic Critical Review. (PubMed, Ther Drug Monit) - "The routine use of costimulation blockade in SOT is hindered by problems in efficacy compared with the standard of care. Costimulatory inhibitors could be combined in a calcineurin inhibitor-free regimen. Future PK/pharmacodynamic studies in costimulatory agents and personalized medicine could warrant TDM of these agents."

Journal • Review • Hepatology • Solid Organ Transplantation • Transplantation • CD40LG • CD80 • TNFSF4

Associations Between Protein Quantitative Trait Loci and Risk of Primary Sjögren's Syndrome: A Mendelian Randomization Study (ACR Convergence 2024) - "We provided genetic evidence further elucidating the complexity of primary Sjögren's disease pathogenesis. Additionally, we suggested a genetic causal link between CD40 and primary Sjögren's disease – supporting the continued investigation of anti-CD40 therapy, such as iscalimab, as a novel treatment for this condition."

IO biomarker • Immunology • Sjogren's Syndrome

A Post-hoc Analysis of Two Phase 2 Randomized Controlled Trials in Patients with Active Sjogren's Disease Exploring the Novel Composite Endpoint Sjögren's Tool for Assessing Response (STAR) (ACR Convergence 2024) - P2 | "Background/Purpose: Two randomized controlled phase 2 trials in patients with active Sjogren's disease (SjD) were recently completed, the LOUiSSe trial assessing the Bruton Tyrosine kinase inhibitor remibrutinib (LOU064; NCT04035668; Dörner et al (1), and the TwinSS trial assessing the fully human monoclonal antibody against CD40, iscalimab (CFZ533; NCT03905525). Our post-hoc exploratory analysis of two recent interventional phase 2 randomized controlled trials suggests utility of STAR as a single composite outcome measure for SjD studies. Encompassing all key disease features, STAR appears to perform well in major subsets of patients with SjD including a subgroup with high symptom burden and low systemic activity. STAR yields a comparatively low placebo response rate, and good differentiation between active and control arms."

Clinical • P2 data • Retrospective data • Fatigue • Immunology • Sjogren's Syndrome • CD40

TWINSS Extn: Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome (clinicaltrials.gov) - P2 | N=206 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Immunology • Sjogren's Syndrome

Study of Efficacy and Safety of Investigational Treatments in Patients With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=248 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Hidradenitis Suppurativa • Immunology

Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig-to-Rhesus Monkey Renal Xenografts. (PubMed, Xenotransplantation) - "It may be reasonable to evaluate an iscalimab-based immunosuppressive regimen in clinical renal xenotransplantation."

Journal • Preclinical • Transplantation • CD40LG • CD55

Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study. (PubMed, Lancet) - P2 | "The study met the primary objective of demonstrating a significant dose-response relationship with iscalimab in terms of disease activity at week 24. Iscalimab was well tolerated and showed initial clinical benefit over placebo in two distinct populations of patients with Sjögren's disease, to be confirmed in larger trials."

Journal • P2b data • Dry Eye Disease • Fatigue • Immunology • Ophthalmology • Rheumatology • Sjogren's Syndrome • CD40

CONTRAIL I: Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Liver Transplant Recipients With Additional 12-month Follow-up and Long-term Extension (clinicaltrials.gov) - P2 | N=128 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; The study was terminated following less favorable efficacy by Iscalimab (CFZ533) in liver transplant patients compared to tacrolimus.

Trial termination • Hepatology • Immunology • Transplant Rejection • Transplantation

SAFETY AND EFFICACY OF ISCALIMAB IN PATIENTS WITH SJÖGREN'S DISEASE: 48-WEEK RESULTS FROM A RANDOMISED, PLACEBO-CONTROLLED, PHASE 2B DOSE-RANGING TRIAL (EULAR 2024) - "By Wk 48, all iscalimab doses showed further improvements in disease activity outcomes and PROs, corroborating the results seen at Wk 24 in two distinct groups of patients with active SjD. Iscalimab's benefit-risk warrants further evaluation."

Clinical • P2b data • Cardiovascular • Congestive Heart Failure • Dry Eye Disease • Fatigue • Heart Failure • Immunology • Infectious Disease • Ophthalmology • Pneumonia • Respiratory Diseases • Sjogren's Syndrome

CCFZ533X2207: Study of Safety and Efficacy of CFZ533 in Type 1 Diabetes Pediatric and Young Adult Subjects (clinicaltrials.gov) - P2 | N=44 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Focus on Sjögren's syndrome - Diagnosis and treatment (PubMed, Dtsch Med Wochenschr) - "A particularly large number of therapeutic approaches are dedicated to the B cell: Rituximab and Belimumab have been included in the EULAR recommendations for serious manifestations and Ianalumab has a promising effect. Another focus of current research is the inhibition of co-stimulation between immune cells. After recent disappointing results for Abatacept, clinical trials show promising effects on Iscalimab and Dazodalibep."

Biomarker • Journal • Review • Cardiovascular • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus

The Immune Landscape in Renal Allograft Rejection is Shaped by Immunosuppression Modality (ATC 2024) - "As different mIS regimens can confer differing susceptibility to later development of antibody-mediated rejection, we examined the effects of mIS on non-T cells (i.e., B cells and myeloid cells) during ACR.* scRNAseq was performed on biopsies of 10 patients undergoing renal allograft rejection (RAR) under 3 maintenance IS therapies (tacrolimus [CNI], belatacept [CTLA4-Ig], and iscalimab [anti-CD40 mAb]). Co-stimulatory blockade mIS regimens reduce the recruitment/accrual of specific populations of activated B cells to kidney allografts compared to tacrolimus mIS."

Antibody-mediated Rejection • Transplant Rejection

Study of Efficacy and Safety of Investigational Treatments in Patients With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Oct 2026 ➔ Nov 2024

Trial primary completion date • Dermatology • Hidradenitis Suppurativa • Immunology

The Efficacy and Safety of Different Targeted Drugs for the Treatment of Generalized Myasthenia Gravis: A Systematic Review and Bayesian Network Meta-analysis. (PubMed, CNS Drugs) - "Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab, the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest CrI of all drugs in this analysis. More well-designed studies with long-term follow-up are needed to further evaluate and compare the efficacy and safety of these drugs in the future."

Retrospective data • Review • CNS Disorders • Myasthenia Gravis

REAL WORLD EXPERIENCE WITH MYCOPHENOLATE MOFETIL IN COMBINATION WITH INTRAVENOUS METHYLPREDNISOLONE FOR MODERATE TO SEVERE THYROID EYE DISEASE: A TERTIARY CENTRE EXPERIENCE (ICE-EDEC 2024) - "Second line treatments are available including tocilizumab, cyclosporine, azathioprine, rituximab, and mycophenolate. A few newer treatments include anti IGF1 monoclonal antibody Teprotumumab, anti FcRN antibody Batoclimab, anti IGF1R inhibitor Linsinitinib, anti TSH receptor antibody and anti-CD-40 antibody Iscalimab... Please note we are currently analysing the data at the time of submission of this abstract and will be happy to share the results and conclusion before publication of the abstract."

Clinical • Combination therapy • Real-world • Real-world evidence • Grave’s Disease • Ophthalmology • Thyroid Eye Disease • IGF1

Assessment of cognitive function in a randomized, placebo-controlled, interventional trial conducted in patients with moderate-to-severe systemic lupus erythematosus (SLE) (LUPUS 2024) - P2 | "In a phase 2 trial (NCT03656562) comprising two separate, placebo-controlled cohorts evaluating ianalumab and iscalimab in patients with SLE of moderate-to-severe activity, we employed Cambridge Automated Neuropsychological Test Battery (CANTAB) assessments to characterize patients’ baseline cognitive function and explore associations with clinical parameters and biomarkers associated with disease severity. We did not detect an ianalumab treatment effect after 28 weeks but cannot exclude the possibility of benefit over longer treatment intervals, or detection by more frequent CANTAB assessments. SLE trials testing treatment effects on cognitive function may benefit from stronger biomarkers to identify individuals experiencing disease-related cognitive dysfunction most likely to benefit from an efficacious therapy."

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

TWINSS Extn: Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Immunology • Sjogren's Syndrome

Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (clinicaltrials.gov) - P2 | N=107 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2024 ➔ Apr 2026 | Trial primary completion date: Sep 2024 ➔ Apr 2026

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

CCFZ533X2207: Study of Safety and Efficacy of CFZ533 in Type 1 Diabetes Pediatric and Young Adult Subjects (clinicaltrials.gov) - P2 | N=44 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2027 ➔ May 2024 | Trial primary completion date: Aug 2025 ➔ Jan 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: A phase 2 randomized study. (PubMed, J Clin Neurosci) - "Iscalimab showed favorable safety and improvements compared with placebo in non-thymectomized patients with moderate-to-severe MG. It did not show any protective effect in patients with moderate-to-severe MG."

Journal • P2 data • CNS Disorders • Myasthenia Gravis

Iscalimab (CFZ533) in Patients with Sjögren’s Disease: Week 24 Efficacy and Safety Results of a Randomized, Placebo-controlled, Phase 2b Dose-ranging Study (ACR Convergence 2023) - "Iscalimab showed a clinically important improvement over placebo in 2 distinct populations of SjD patients and was well tolerated without obvious safety signals. Figure 1: Least-square mean of change from baseline in ESSDAI scores over time up to Week 24 and estimated dose-response curve in Cohort 1 Figure 2: Least-square mean of change from baseline in patient-reported outcomes (secondary outcome measures) and pharmacodynamic markers up to Week 24 in Cohort 1 Figure 3. Least-square mean of change from baseline in ESSPRI and its subdomains and whole salivary flow up to Week 24 in Cohort 2 B. A Fisher: Bristol-Myers Squibb(BMS), 2, Celgene, 5, Galapagos, 2, 5, Janssen, 2, 5, Novartis, 2, Roche, 2, Sanofi, 2, Servier, 2, 5, UCB, 2; X. Mariette: AstraZeneca, 2, 6, BMS, 2, 6, Galapagos, 2, 6, GSK, 2, 6, Novartis, 2, 6, Pfizer, 2, 6; A. S Papas: Novartis, 1, 5; T. Grader-Beck: IQVIA, 2, Novartis, 2;"

Clinical • IO biomarker • P2b data • Dry Eye Disease • Fatigue • Immunology • Infectious Disease • Ophthalmology • Sjogren's Syndrome • CD40