Amgen's dazodalibep hits primary endpoint in Phase 3 systemic Sjögren's disease trial
核心洞察
Amgen reported positive topline results from the Phase 3 OASIZ 301 study of dazodalibep in adults with moderate-to-severe systemic Sjögren's disease (搜索) activity.
The trial met its primary endpoint, showing statistically significant and clinically meaningful improvement in ESSDAI score at Week 48 versus placebo.
Improvements in ESSDAI were observed as early as Week 4 and were sustained through Week 48 of the randomized, double-blind study.
Amgen reported positive topline results from the Phase 3 OASIZ 301 study of dazodalibep in adults with Sjögren's disease (搜索) and moderate-to-severe systemic disease activity. 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). Improvements in ESSDAI were observed as early as Week 4 and were sustained through Week 48.
ESSDAI is a validated clinical tool used to assess systemic disease activity across organ systems in patients with Sjögren's disease (搜索). Amgen said detailed data from OASIZ 301 will be presented at an upcoming medical meeting. No numerical results, including mean changes, hazard ratios or p-values, were disclosed in the topline release.
Trial design and endpoints
OASIZ 301 is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of dazodalibep in patients with Sjögren's disease (搜索) with moderate-to-severe systemic disease activity, defined as an ESSDAI score of 5 or above. The study enrolled approximately 621 patients. The primary endpoint was change from baseline in ESSDAI score at Week 48.
Key secondary endpoints evaluated dryness, tender and swollen joints, fatigue, and ESSDAI[5] response, defined as a decrease of at least 5 points from baseline.
Safety profile
The most common adverse events, reported at an incidence of 5% or greater and at a higher rate in the dazodalibep arm compared with placebo, were nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions. Amgen described these events as generally mild to moderate in nature. Discontinuations due to adverse events occurred at a low rate and were balanced across treatment groups. No imbalance in the incidence of thromboembolic events or opportunistic infections was observed across treatment arms.
Mechanism and competitive landscape
Dazodalibep is a potential first-in-class CD40L (搜索) antagonist fusion protein designed to target immune activation by disrupting interactions between T cells, B cells and other antigen-presenting cells. The agent blocks the CD40L-CD40 co-stimulatory interaction, disrupting upstream immune activation that drives Sjögren's disease (搜索) pathology. This mechanism distinguishes it from pipeline competitors targeting downstream B cell biology: Novartis's ianalumab depletes B cells via BAFF-R (搜索) blockade, and Johnson & Johnson's nipocalimab reduces circulating IgG autoantibodies by inhibiting the neonatal Fc receptor (搜索).
Novartis received FDA Breakthrough Therapy Designation for ianalumab in Sjögren's disease (搜索) in January 2026 and has been reported to be targeting a US launch in the second half of 2026. China-based RemeGen's telitacicept, a dual BAFF/APRIL inhibitor, received China NMPA approval for Sjögren's disease in June 2026 but holds no FDA or EMA approval in this indication.
The only currently approved therapies for Sjögren's disease (搜索), pilocarpine and cevimeline, are oral muscarinic agonists that address dry mouth symptoms and have no effect on systemic disease activity. There are no FDA-approved medicines for Sjögren's disease.
Disease burden
Sjögren's disease (搜索) is a heterogeneous systemic autoimmune disease that affects the entire body. Along with symptoms of extensive dryness, other serious manifestations may include profound fatigue, chronic pain, major organ involvement, neuropathy, and an increased risk of lymphoma. Although SjD is the second most common autoimmune rheumatic disease, it remains widely underrecognized, with the full extent of its systemic severity and symptomatic impact often underestimated. Many patients continue to experience persistent systemic disease activity and debilitating symptoms.
"The results mark an important step forward for people living with Sjögren's disease (搜索), a condition with significant unmet need and no approved systemic treatment options," said Jay Bradner, M.D., executive vice president, Research and Development, Artificial Intelligence and Data at Amgen. "The rapid and sustained improvement observed in systemic disease activity reinforces our confidence in dazodalibep and the broader Phase 3 program as we work to deliver a new, highly differentiated option for people living with this debilitating autoimmune disease."
Ghaith Noaiseh, M.D., Associate Professor of Medicine in the Division of Allergy, Clinical Immunology and Rheumatology at the University of Kansas Medical Center and lead investigator of the study, said patients with Sjögren's disease (搜索) contend with debilitating symptoms and systemic manifestations for which no approved disease-modifying therapy exists. "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," he said.
Janet E. Church, President and Chief Executive Officer of the Sjögren's Foundation, said the disease is complex and heterogeneous, and can be relentless, creating a real burden for people living with it and affecting their quality of life. "The Sjögren's Foundation welcomes continued progress in research that expands the possibilities for people living with Sjögren's disease (搜索) and moves us toward a future with more treatment options and better care," she said.
Broader development program
Dazodalibep is being studied in two Sjögren's disease (搜索) patient groups: those with moderate-to-severe systemic disease and those with high symptom burden and low systemic disease who suffer from dryness, fatigue, and/or pain that profoundly impact daily life.
OASIZ 303, a Phase 3, randomized, double-blind, placebo-controlled study evaluating dazodalibep in patients with high symptom burden and low systemic Sjögren's disease (搜索) activity, is expected to complete in Q4 2026. Amgen is also conducting OASIZ 304, an open-label, long-term extension study evaluating the long-term safety and tolerability of dazodalibep in eligible participants from OASIZ 301 and OASIZ 303. Amgen has not disclosed a regulatory filing timeline.