dazodalibep (HZN-4920) / Amgen - LARVOL DELTA

Amgen…announced positive topline results from the Phase 3 OASIZ 301 study evaluating dazodalibep in adults with Sjögren's disease and moderate-to-severe systemic disease activity. (PRNewswire) - "The study met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement at Week 48, as measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Notably, improvements in ESSDAI were observed as early as Week 4 with treatment with dazodalibep, which were sustained through Week 48 of the study. ESSDAI is a validated clinical tool used to assess systemic disease activity across organ systems in patients with Sjögren's disease...The most common adverse events (>/= 5% incidence, reported at a higher rate in dazodalibep compared with placebo) were nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions, and were generally mild to moderate in nature...The company plans to present detailed data from the OASIZ 301 study at an upcoming medical meeting....The Phase 3 OASIZ 303 study of dazodalibep in moderate-to-severe symptomatic Sjögren's disease is expected to complete in Q4 2026."

P3 data: top line • Trial completion date • Immunology • Sjogren's Syndrome

An Fc-Free CD40L-Targeting Tn3 Scaffold (Dazodalibep) Demonstrates Absence of Platelet Activation and Thrombotic Risk Across Preclinical Models (ACR Convergence 2026) - No abstract available

Preclinical • Immunology • Inflammation • CD40LG

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

Re-engineering CD154 blockade for transplantation: Fc-free design to separate thrombotic risk from therapeutic function. (PubMed, Clin Transplant Res) - "Size-based carriers recover only the second: conjugation of polyethylene glycol (PEG) to an anti-CD154 Fab' extends its half-life from hours to weeks, as in dapirolizumab pegol, but leaves FcRn recycling unaddressed, while uncertainties remain regarding long-term PEG exposure. Albumin recovers both through FcRn-dependent recycling and its own molecular size, without engaging Fcγ receptors. Dazodalibep, an Fc-free albumin-fusion CD154 antagonist, was administered with belatacept to kidney transplant recipients in a single-arm phase 2a trial without thrombotic events, but the prespecified composite efficacy endpoint was not met."

Journal • Review • Cardiovascular • Transplant Rejection • Transplantation • CD40 • CD40LG

VIBRANT: VIB4920 for Active Lupus Nephritis (clinicaltrials.gov) - P2 | N=74 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2027 ➔ Dec 2028 | Trial primary completion date: Aug 2026 ➔ Jun 2028

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

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=651 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Immunology • Sjogren's Syndrome

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

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

Dazodalibep is a fusion protein that inhibits CD40 ligand (CD40L). (PRNewswire) - "Two Phase 3 studies of dazodalibep in Sjögren's disease are underway. The first study is ongoing in patients with moderate-to-severe systemic disease activity. The second study is ongoing in patients with moderate to high symptom burden with low systemic disease activity. Completion of both studies is expected in H2 2026."

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

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

The Sjögren’s Tool for Assessing Response (STAR) demonstrates its ability to accurately detect treatment efficacy in 15 recent RCTs in Sjögren’s disease (EULAR 2026) - P2, P3 | "Methods Data from 15 trials used for STAR development (Abatacept (ASAP-III), leflunomide + hydroxychloroquine (REPURP-SS) and rituximab (TEARS and TRACTISS), the iscalimab and ianalumab phase 2 trials, Baminercept, hydroxychloroquine (JOQUER), tocilizumab (ETAP) and 6 other independent clinical trials (GSK (NCT02631538), Belimumab + Rituximab, Belimumab, Rituximab versus placebo and BMS Abatacept (NCT02915159 presentation (Servier, anti-IL7 NCT04605978; Novartis : Remibrutinib (NCT04035668) and Iscalimab (), leflunomide + hydroxychloroquine (REPURP-SS). Data from Dazodalibep (Amgen, CD40L antagonist NCT04129164) to be present during full analysis)...Conclusions In this analysis based on 15 trials, the STAR candidate, and some alternatives options, appears to detect treatment response accurately, with a high sensitivity to change for treatments showing a beneficial effect. Additionally, it exhibits specificity to change by not falsely detecting improvement in..."

Clinical • Sjogren's Syndrome • CD40LG • IL7

Efficacy and safety of pharmacological treatment for Sjögren's disease: a network meta-analysis. (PubMed, Z Rheumatol) - "Compared to PBO, iscalimab, dazodalibep, iguratimod, remibrutinib, leflunomide + hydroxychloroquine, ianalumab, and filgotinib significantly reduced the ESSDAI score, with no distinctions in the ESSPRI score. No significant differences in safety profiles were fond between any drugs and PBO."

Journal • Retrospective data • Review • Dry Eye Disease • Immunology • Ophthalmology • Rheumatology • Sjogren's Syndrome • Xerostomia

Two Phase 3 studies of dazodalibep in Sjögren's disease are underway. (Amgen Press Release) - "The first study is ongoing in patients with moderate-to-severe systemic disease activity. The second study is ongoing in patients with moderate to high symptom burden with low systemic disease activity. Completion of both studies is expected in H2 2026."

Trial completion date • Immunology • Sjogren's Syndrome

Pathophysiological aspects of primary Sjögren's disease : From epithelial activation to systemic autoimmunity (PubMed, Z Rheumatol) - "The pathophysiology of SjD is a multistage process in which the early activation of the salivary epithelium and subsequent activation of the innate immune system with IFN play a crucial role in its initiation. This is followed by activation of the adaptive immune system with a focus on T‑B cell interaction and pathological B cell activation. The chronic inflammation in SjD can be understood as positive feedback from the activation of the innate and adaptive immune systems, which innovative therapeutic approaches aim to interrupt. These comprise TLR and IFN blockade, inhibition of T‑B cell interaction via CD154/CD40 blockade (e.g., dazodalibep, iscalimab) or B cell depletion strategies including. anti-BAFF‑R and anti-CD19 CAR-T cells."

Journal • Review • Immunology • Inflammation • Sjogren's Syndrome • CD40 • CD40LG

Dazodalibep: Sjögren’s syndrome phase III program and timing (MarketBeat) - "The company said it expects phase III results in the second half of this year."

P3 data • Sjogren's Syndrome

Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection. (PubMed, Am J Transplant) - "No thrombotic events were observed. While the prespecified primary endpoint to prevent composite efficacy failure was not met among patients who completed this study, dazodalibep and belatacept dual biologic treatment was generally safe, well tolerated, and effective as the sole maintenance antirejection therapy."

Journal • Antibody-mediated Rejection • Immunology • Solid Organ Transplantation • Transplant Rejection • Transplantation • CD40LG • CD80

CONTROL-RA: CD40L Antagonism in Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Apr 2029 ➔ Jul 2025 | Withdrawn ➔ Terminated | Trial primary completion date: Sep 2028 ➔ Jul 2025; The study is being closed early due to insufficient participant enrollment across study sites.

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

A Long-term Extension Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) (clinicaltrials.gov) - P3 | N=844 | Recruiting | Sponsor: Amgen | Trial completion date: Aug 2029 ➔ Dec 2029 | Trial primary completion date: Aug 2029 ➔ Dec 2029

Trial completion date • Trial primary completion date • 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=434 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Sjogren's Syndrome

Plain language summary: treatment of Sjögren's disease with dazodalibep. (PubMed, Immunotherapy) - No abstract available

Journal • Sjogren's Syndrome

Humanistic Burden of Sjögren's Disease: A Systematic Review of Treatment Efficacy on Health-Related Quality-of-Life (ACR Convergence 2025) - "In randomized controlled trials (RCTs) involving rituximab, leniolisib, and abatacept, no significant differences in ESSPRI scores were found between treatment and placebo groups, indicating similar levels of symptom burden reduction (Table 2). In contrast, iguratimod and dazodalibep demonstrated significant improvements in overall ESSPRI scores compared to placebo in small or local trials. An RCT of tocilizumab failed to show significant improvements in anxiety or depression outcomes compared to the control group (Table 3)... Both systemic treatments and non-pharmacological interventions have generally shown limited efficacy in reducing the HRQoL burden in SjD. Although some treatments have demonstrated potential, these findings are primarily derived from clinical studies with small sample sizes and require validation. There remains a significant unmet need for therapies that can effectively alleviate the quality-of-life burden in patients with SjD."

Clinical • HEOR • Review • CNS Disorders • Depression • Fatigue • Hematological Malignancies • Immunology • Lymphoma • Mood Disorders • Psychiatry • Sjogren's Syndrome • Xerostomia

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=651 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Sjogren's Syndrome

CONTROL-RA: CD40L Antagonism in Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=104 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Novel Anti-CD154 Nonantibody Fusion Protein Facilitates Long Term Pig to Primate Kidney Xenograft Survival (WTC 2025) - "Here we investigated the use of Dazodalibep to prevent rejection in a pig-to-primate kidney transplant model.* GGTA1 knockout/CD55 transgenic pig kidneys were transplanted into rhesus monkeys (n = 6) receiving treatment with anti-CD4 (day -6 and 0) and anti-CD20 (day 0) depletion and maintenance with mycophenolate mofetil and steroids. A Dazodalibep based immunosuppression regimen resulted in median survival >1 year in a pig-to-primate xenograft kidney model, including the longest reported surviving xenograft >4 years. Importantly, we observed no thromboembolic complications or adverse effects using this novel nonantibody fusion protein. Blockade of the CD40/154 pathway with Dazodalibep represents a promising treatment strategy for clinical renal xenotransplantation."

Cardiovascular • CD40 • CD40LG • CD55

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