Dazodalibep OASIZ-301 trial design and primary ESSDAI results
Dazodalibep met its primary endpoint in the phase 3 OASIZ-301 trial, demonstrating a statistically significant and clinically meaningful improvement in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score, a composite measure of systemic disease activity across 12 organ domains, at week 48 in patients with moderate-to-severe systemic Sjögren's disease, Amgen announced September 22, 2026.¹ Amgen did not disclose specific numerical results, effect sizes, or p-values for the primary endpoint in its announcement.¹
Dazodalibep is a potential first-in-class CD40 ligand (CD40L) antagonist fusion protein designed to disrupt costimulatory interactions between T cells, B cells, and antigen-presenting cells.¹ No United States Food and Drug Administration (FDA)-approved systemic treatments currently exist for moderate-to-severe systemic Sjögren's disease.¹ Amgen said detailed OASIZ-301 data will be presented at an upcoming medical meeting.¹
OASIZ-301 is a phase 3, randomized, double-blind, placebo-controlled trial enrolling approximately 621 patients with Sjögren's disease and an ESSDAI score of 5 or greater, reflecting moderate-to-severe systemic disease activity.¹ The trial evaluated dazodalibep against placebo, with a primary endpoint of change in ESSDAI score from baseline at week 48.¹ OASIZ-301 follows a placebo-controlled phase 2 trial of dazodalibep in Sjögren's disease, which also met its primary endpoint and was published in Nature Medicine.²
Improvement in ESSDAI score was observed as early as week 4 and was sustained through week 48, according to Amgen.¹ The company characterized the effect as both statistically significant and clinically meaningful without providing the underlying effect size or confidence interval.¹ Exact numerical results for the primary endpoint were not included in the topline announcement.¹
What were Dazodalibep secondary endpoints and safety in systemic Sjögren's disease?
Secondary endpoints in OASIZ-301 included measures of dryness, joint symptoms, fatigue, and ESSDAI response, defined as a decrease of 5 points or greater from baseline.¹ Amgen did not report numerical secondary endpoint data in its September 22 announcement.¹ The company said secondary endpoint data will be included when detailed OASIZ-301 results are presented at a future medical meeting.¹
Key Facts
Did dazodalibep meet its primary endpoint in the OASIZ-301 trial?
Amgen reported dazodalibep met its primary endpoint of change in ESSDAI score at week 48, with a statistically significant and clinically meaningful improvement versus placebo, though specific numerical results were not disclosed.¹
What is dazodalibep's mechanism of action?
Dazodalibep is a potential first-in-class CD40 ligand (CD40L) antagonist fusion protein designed to disrupt costimulatory interactions between T cells, B cells, and antigen-presenting cells.¹
What safety findings were reported in OASIZ-301?
The most common adverse events occurring in 5% or more of dazodalibep-treated patients included nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions, generally mild to moderate, with low discontinuation rates and no imbalance in thromboembolic events or opportunistic infections.¹
The most common adverse events (AEs) occurring in 5% or more of dazodalibep-treated patients and at a higher incidence than placebo included nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions, generally mild to moderate in severity.¹ Discontinuations due to adverse events were low, according to Amgen.¹ No imbalance in thromboembolic events or opportunistic infections was observed between treatment arms.¹
Ghaith Noaiseh, MD, associate professor of medicine, Division of Allergy, Clinical Immunology and Rheumatology, University of Kansas Medical Center, and OASIZ-301 lead investigator, said, “These topline results provide further support for dazodalibep as an emerging treatment for improving systemic disease activity and represent an important advance for the field.”¹
Janet E. Church, president and chief executive officer, Sjögren's Foundation, said, “The Sjögren's Foundation welcomes continued progress in research that expands the possibilities for people living with Sjögren's disease.”¹
Amgen said a companion phase 3 trial, OASIZ-303, evaluating dazodalibep in patients with symptomatic Sjögren's disease and low systemic disease activity, is expected to complete in the fourth quarter of 2026.¹ An open-label long-term extension study, OASIZ-304, is also ongoing.¹ Together, the three trials comprise Amgen's OASIZ clinical development program evaluating dazodalibep across the spectrum of Sjögren's disease severity.¹
References
St. Clair EW, Baer AN, Ng WF, et al. CD40 ligand antagonist dazodalibep in Sjögren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. Nat Med. 2024;30(6):1583-1592. doi:10.1038/s41591-024-03009-3
