dazodalibep (HZN-4920) / Amgen - LARVOL DELTA

HZNP-DAZ-303: A Safety and Efficacy Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-Severe Symptom State (clinicaltrials.gov) - P3 | N=435 | Recruiting | Sponsor: Amgen | Trial completion date: Aug 2026 ➔ Nov 2026 | Trial primary completion date: Aug 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Immunology • Sjogren's Syndrome

A Long-term Extension Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) (clinicaltrials.gov) - P3 | N=844 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Sjogren's Syndrome

CONTROL-RA: CD40L Antagonism in Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=104 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Recruiting | Trial completion date: Mar 2026 ➔ Apr 2029 | Trial primary completion date: Aug 2025 ➔ Sep 2028

Enrollment open • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

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

A Phase 1b Study of MEDI4920 in Participants With Adult-onset Rheumatoid Arthritis (clinicaltrials.gov) - P1 | N=57 | Completed | Sponsor: Amgen | Phase classification: P1b ➔ P1

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Safety and Efficacy of Dual Costimulation Blockade With VIB4920 and Belatacept for Prophylaxis of Allograft Rejection in Adults Receiving a Kidney Transplant (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Amgen | Phase classification: P2a ➔ P2

Phase classification • Immunology • Transplant Rejection • Transplantation

A Long-term Extension Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) (clinicaltrials.gov) - P3 | N=844 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Immunology • Sjogren's Syndrome

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

CONTROL-RA: CD40L Antagonism in Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=104 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

CD40L BLOCKADE WITH DAZODALIBEP SIGNIFICANTLY IMPROVES DISEASE ACTIVITY, SWOLLEN AND TENDER JOINT COUNTS, WHILE REDUCING MULTIPLE T- AND B-CELL BIOMARKERS IN THE MIDORA PHASE 2 STUDY OF PATIENTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS (EULAR 2024) - P2 | " This biomarker study focused on a total of 47 adult patients with moderate-to-severe active RA that responded inadequately to methotrexate, other conventional disease-modifying anti-rheumatic drugs, or tumor necrosis factor-α inhibitors. DAZ-mediated CD40L blockade in patients with moderate-to-severe active RA demonstrated significant improvements in disease activity scores such as DAS28-CRP, Patient Global Assessment, SDAI, CDAI, and Physician Global Assessment including tender and swollen joint counts. Additionally, DAZ reduced biomarkers of T- and B-cell costimulatory blockade, and inhibition of GC formation activity, and autoantibody production. Together, these data demonstrate the biological impact of CD40-CD40L pathway blockade on selected blood biomarkers in RA."

Biomarker • Clinical • IO biomarker • P2 data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • CD27 • CD40LG • CRP • CXCL13 • CXCR5 • ICOS • ITGAX

DAZODALIBEP (ANTI-CD40L) EFFECTIVELY REDUCES MULTIPLE PROTEINS ASSOCIATED WITH B-, T-, AND DENDRITIC CELL BIOMARKERS IN SJӦGREN'S DISEASE: CORROBORATION OF IMMUNOPHENOTYPING FINDINGS FROM THE ALISS PHASE 2 STUDY (EULAR 2024) - P2 | "Compared to a healthy cohort, serum proteomics profiling revealed a core set of 29 biomarkers elevated in subjects with Sjogren's disease at baseline and were associated with inflammatory and adaptive immune responses, particularly activation of B-, T-, and dendritic cells. Importantly, these biomarkers were shown to be significantly reduced by DAZ. These proteomics findings corroborate previous immunophenotyping flow cytometry data from the ALISS phase 2 study that demonstrated significant reductions of B and T cell activation and proliferation by DAZ in subjects with Sjogren's disease across populations with either moderate-to-severe disease activity or high symptomatic burden."

Biomarker • P2 data • Immunology • Sjogren's Syndrome • CD40LG • CD63 • LAMP3 • POP1

AMGEN TO PRESENT INNOVATIVE RHEUMATOLOGY RESEARCH AT EULAR 2024 (PRNewswire) - "Amgen...announced the presentation of data across its diverse portfolio and pipeline at the European Alliance of Associations for Rheumatology's (EULAR) 2024 Congress, June 12-15 in Vienna....Key presentations include the first findings showing dazodalibep improved major biomarkers in Sjögren's disease, as well as data on treatment outcomes for uncontrolled gout based on a post-hoc analysis of the MIRROR trial for KRYSTEXXA (pegloticase) with methotrexate."

P2 data • Retrospective data • Rheumatoid Arthritis • Sjogren's Syndrome

VIBRANT: VIB4920 for Active Lupus Nephritis (clinicaltrials.gov) - P2 | N=74 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Recruiting | Phase classification: P2a ➔ P2

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

CD40 ligand antagonist dazodalibep in Sjögren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. (PubMed, Nat Med) - P2 | "In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 ."

Clinical • Journal • P2 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Musculoskeletal Pain • Nephrology • Novel Coronavirus Disease • Pain • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • CD40LG

A Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-severe Systemic Disease Activity (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Amgen | Trial primary completion date: Feb 2026 ➔ Jul 2026

Trial primary completion date • Immunology • Sjogren's Syndrome

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

HZNP-DAZ-303: A Safety and Efficacy Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-Severe Symptom State (clinicaltrials.gov) - P3 | N=435 | Recruiting | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Sjogren's Syndrome

HZNP-DAZ-303: A Safety and Efficacy Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-Severe Symptom State (clinicaltrials.gov) - P3 | N=435 | Not yet recruiting | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland

New P3 trial • Immunology • Sjogren's Syndrome

CONTROL-RA: CD40L Antagonism in Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=104 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-severe Systemic Disease Activity (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Sjogren's Syndrome

Correction: The MIDORA trial: a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study of the efficacy and safety of dazodalibep in patients with rheumatoid arthritis. (PubMed, RMD Open) - No abstract available

Journal • P2 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Dazodalibep, a CD40L Antagonist, in a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Trial of Subjects with Sjögren’s Disease Having Unacceptable Symptomatic Burden but Limited Extraglandular Organ Involvement (ACR Convergence 2023) - P2 | "The results during Stage II provide further evidence of the clinical efficacy of DAZ in Sjögren’s disease and support the primary endpoint result. DAZ was generally safe and well tolerated in Stage II, although larger trials of DAZ therapy for this indication are warranted to further explore its safety profile and confirm its clinical efficacy."

Clinical • Late-breaking abstract • P2 data • Breast Cancer • Cardiovascular • Fatigue • Immunology • Infectious Disease • Nephrology • Oncology • Sjogren's Syndrome • Solid Tumor • CD40LG

Population Pharmacokinetic/Pharmacodynamic Modeling of Dazodalibep, a CD40L Antagonist, in Healthy Volunteers and Patients with Rheumatoid Arthritis and Sjogren’s Syndrome (ACR Convergence 2023) - "The PK and PK/PD of DAZ were successfully described by population modeling. The modeling results supported the selection of dose to be further evaluated in upcoming phase 3 studies."

Clinical • IO biomarker • PK/PD data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • CD40LG • CXCL13

CD40L Inhibition with Dazodalibep Rapidly Reduces Blood Biomarkers of T and B Cell Costimulation in Subjects with Sjögren’s Having High Disease Activity or High Symptom Burden (ACR Convergence 2023) - P2 | "DAZ-mediated CD40-CD40L blockade in subjects with Sjögren's disease reduced biomarkers by inhibiting T/B cell costimulation and downstream biomarkers of GC formation, activity, and autoantibody production. These findings demonstrate the biological impact of DAZ in subjects with Sjogren's across populations with either moderate-to-severe systemic disease activity or unacceptable symptom burden. Impact of dazodalibep on blood biomarkers of T and B cell costimulation in Population 1: Subjects with moderate-to-severe systemic disease activity."

Biomarker • Clinical • IO biomarker • Immunology • Rheumatoid Arthritis • Sjogren's Syndrome • CD27 • CD40LG • CXCL13 • CXCR5 • ICOS • ITGAX