Amgen’s dazodalibep meets Phase 3 endpoints in OASIZ-301, reducing systemic disease activity and improving patient-reported dryness in Sjögren’s disease.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Amgen announced positive Phase 3 results on November 11, 2026, for its investigational CD40 ligand (CD40L) antagonist dazodalibep in adults with Sjögren’s disease. In the OASIZ-301 study, both tested dosing regimens significantly reduced systemic disease activity compared with placebo at Week 48. The 1,500 mg every-four-week regimen also achieved significant improvements in patient-reported dryness across two assessment measures, extending the efficacy findings beyond systemic disease activity.
The results will be presented during a late-breaking session (LB22) at the American College of Rheumatology (ACR) Convergence 2026.
OASIZ-301 Trial Design and Patient Population
OASIZ-301 was a randomized, double-blind, placebo-controlled Phase 3 study involving 648 adults with Sjögren’s disease and moderate-to-severe systemic disease activity, defined by an ESSDAI score of at least 5. Participants had a mean baseline European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index (ESSDAI) score of 10.2.
Participants received dazodalibep 1,500 mg every four weeks, 3,000 mg every 12 weeks, or placebo. The primary endpoint was change in ESSDAI score from baseline at Week 48. Key secondary endpoints included dryness, tender and swollen joints, fatigue and ESSDAI response, defined as a reduction of at least five points from baseline.
Both Dosing Regimens Met the Primary Endpoint
The 1,500 mg every-four-week regimen (n=217) produced a least-squares mean reduction of 5.6 points from baseline, compared with 3.8 points with placebo. The placebo-adjusted difference was 1.8 points (adjusted p<0.001).
Similarly, the 3,000 mg every-12-week regimen (n=217) reduced ESSDAI scores by 5.2 points, compared with 3.8 points with placebo, representing a placebo-adjusted difference of 1.4 points (adjusted p=0.010).
Treatment effects were observed as early as Week 4 and sustained through Week 48. Although both regimens demonstrated statistically significant improvements, the reported results do not establish the superiority of one dosing schedule over the other.
Every-Four-Week Dosing Improved Patient-Reported Dryness
Beyond systemic disease activity, the every-four-week regimen significantly improved patient-reported dryness at Week 48. The placebo-adjusted least-squares mean differences in change from baseline were −1.17 points on the dryness domain of the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI) and −0.93 points on the Diary for Assessing Sjögren’s Patient-Reported Index (DASPRI). Both comparisons achieved adjusted p-values below 0.001.
The mean changes from baseline were −2.50 versus −1.33 points for ESSPRI dryness and −1.98 versus −1.05 points for DASPRI dryness, comparing dazodalibep with placebo, respectively.
Additional Efficacy Findings
Amgen also reported greater proportions of patients achieving ESSDAI reductions of at least 3, 5 or 7 points with dazodalibep than placebo. Total ESSPRI and DASPRI scores favoured treatment over 48 weeks, with mean improvement in total ESSPRI exceeding 1.5 points with both regimens.
Improvements were also observed across ESSDAI domains, including constitutional, glandular, articular, lymphadenopathy, cutaneous and biological manifestations.
More patients receiving dazodalibep achieved the Sjögren’s Tool for Assessing Response (STAR) composite response, which incorporates patient-reported symptoms and objective disease-activity measures. Greater increases in stimulated salivary flow, an objective measure relevant to glandular function, were also reported. However, numerical effect sizes for these additional findings were not provided in the announcement.
Dazodalibep’s Mechanism of Action
Dazodalibep is an investigational CD40 ligand (CD40L) antagonist fusion protein designed to disrupt interactions between T cells, glandular epithelial cells, B cells and other antigen-presenting cells.
By modulating CD40L-mediated immune signalling, the therapy aims to reduce immune activation associated with Sjögren’s disease. This mechanism provides the biological rationale for evaluating dazodalibep against both systemic disease activity and patient-reported manifestations.
Sjögren’s Disease: Clinical Background
Sjögren’s disease is a chronic autoimmune condition affecting moisture-producing glands and, in some patients, multiple organs. Persistent dryness, fatigue and joint pain can substantially affect daily life, while systemic inflammation may involve constitutional, glandular, articular and other organ manifestations.
The heterogeneous nature of the disease creates treatment challenges that extend beyond managing individual symptoms. As of the November 2026 announcement, no treatment was FDA-approved specifically for Sjögren’s disease.
Safety and Tolerability
The most common adverse events occurring at an incidence of at least 5% and at a higher rate with dazodalibep than placebo were nasopharyngitis, urinary tract infection, hypertension and infusion-related reactions. These events were generally mild to moderate.
Serious adverse events and treatment discontinuations due to adverse events were balanced across all three groups. No imbalance was observed in thromboembolic events or opportunistic infections, while malignancy rates were low and comparable between groups.
Continued follow-up will be important to characterise uncommon and longer-term risks.
Ongoing Clinical Development
Amgen is evaluating dazodalibep in the separate Phase 3 OASIZ-303 study, which targets patients with high symptom burden but low systemic disease activity. This population differs from the moderate-to-severe systemic disease population enrolled in OASIZ-301.
The company is also conducting OASIZ-304, an open-label long-term extension study assessing safety and tolerability in eligible participants from OASIZ-301 and OASIZ-303.
Clinical Interpretation
OASIZ-301 provides a positive Phase 3 efficacy signal across two distinct dimensions of Sjögren’s disease. Both regimens reduced systemic disease activity, while every-four-week dosing additionally demonstrated significant improvements in patient-reported dryness. These outcomes are complementary: ESSDAI measures systemic disease activity, whereas ESSPRI and DASPRI capture patients’ symptom experience.
The findings support further evaluation of CD40L blockade as a potential therapeutic approach, particularly in patients with moderate-to-severe systemic disease activity. However, the results should not be generalised to patients whose disease is predominantly characterised by symptoms despite low systemic activity.
Dazodalibep remains investigational and is not FDA-approved. Full clinical data and longer-term follow-up will be important to assess the durability and clinical relevance of treatment benefits and clarify its potential role across different Sjögren’s disease populations.
Reference
Amgen Announces Positive Phase 3 Results for Dazodalibep in Sjögren’s Disease. Amgen, November 11, 2026.
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 ID NCT06104124
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.