Amgen announced positive topline results from the phase 3 OASIZ 301 trial of dazodalibep in adults with Sjögren disease and moderate-to-severe systemic disease activity, meeting its primary endpoint with statistically significant and clinically meaningful improvement at week 48, the company announced September 22, 2026.¹ Improvements in disease activity, as measured by the EULAR Sjögren Syndrome Disease Activity Index (ESSDAI), were observed as early as week 4 and sustained through week 48.¹
Key facts
- Drug: Dazodalibep (Amgen)
- Class: CD40 ligand antagonist fusion protein (potential first-in-class)
- Indication: Sjögren disease, moderate-to-severe systemic disease activity
- Trial: Phase 3 OASIZ 301 (NCT06104124); ~621 patients, randomized, double-blind, placebo-controlled
- Primary result: ESSDAI improvement at week 48
- Onset: Improvements observed as early as week 4
- Prior data: Phase 2 showed 6.3-point vs 4.1-point ESSDAI reduction at day 169
- Regulatory status: No FDA-approved therapies currently exist Sjögren disease
- Pipeline: OASIZ 303 trial (low systemic activity population) expected to complete Q4 2026
"The results mark an important step forward for people living with Sjögren's disease, a condition with significant unmet need and no approved systemic treatment options," said Jay Bradner, MD, executive vice president of research and development, artificial intelligence and data at Amgen, in a company press release.¹ "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."
What did the OASIZ 301 trial evaluate?
OASIZ 301 (NCT06104124) is a phase 3, randomized, double-blind, placebo-controlled trial that enrolled approximately 621 patients with Sjögren disease and moderate-to-severe systemic disease activity, defined as an ESSDAI score of 5 or higher.¹,² The primary endpoint was change from baseline in ESSDAI score at week 48, and key secondary endpoints evaluated dryness, tender and swollen joints, fatigue, and ESSDAI response, defined as a decrease of at least 5 points from baseline. The most common adverse events occurring in 5% or more of patients and at a higher rate than placebo were nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions, generally mild to moderate in severity; discontinuations due to adverse events were low and balanced across treatment groups, and no imbalance in thromboembolic events or opportunistic infections was observed.¹
How does dazodalibep work, and what has earlier data shown?
Dazodalibep is a potential first-in-class CD40 ligand antagonist fusion protein designed to disrupt costimulatory interactions between T cells, B cells, and other antigen-presenting cells.¹ In an earlier phase 2 crossover trial in patients with moderate-to-severe systemic disease activity, dazodalibep produced a 6.3-point reduction in ESSDAI score compared with a 4.1-point reduction for placebo at day 169, and, unlike first-generation anti-CD40L monoclonal antibodies, dazodalibep has not shown a thromboembolic safety signal in clinical trials to date.³
What did outside experts say about the results?
"Patients with Sjogren's disease contend with debilitating symptoms and systemic manifestations for which no approved disease-modifying therapy exists," said Ghaith Noaiseh, MD, associate professor of medicine, Division of Allergy, Clinical Immunology and Rheumatology at the University of Kansas Medical Center, and lead investigator of the OASIZ 301 study, in the release.¹
Janet E. Church, president and CEO, Sjögren's Foundation, said in the release that the results move the field "toward a future with more treatment options and better care" for patients living with a disease that can be relentless and affects everyone differently.¹
Why is a new treatment needed for Sjögren disease, and what's next?
Sjögren disease is the second most common autoimmune rheumatic disease but remains widely underrecognized, and there are currently no FDA-approved medicines for the condition, according to Amgen. Symptoms can include profound fatigue, chronic pain, major organ involvement, neuropathy, and increased lymphoma risk, alongside extensive dryness.¹ Amgen plans to present detailed OASIZ 301 data at an upcoming medical meeting, and a related phase 3 trial, OASIZ 303, evaluating dazodalibep in patients with high symptom burden but low systemic disease activity, is expected to be completed in the fourth quarter of 2026.¹
What are the limitations?
These are topline results, and detailed statistical data have not yet been published in a peer-reviewed journal or presented in full at a medical meeting. Dazodalibep remains investigational and has not been approved by FDA or any other regulatory authority.
References
- Amgen. Amgen announces positive topline Phase 3 results for dazodalibep in moderate-to-severe systemic Sjögren's disease. Press release. Published September 22, 2026. Accessed September 23, 2026. https://www.amgen.com/newsroom/press-releases/2026/09/amgen-announces-positive-topline-phase-3-results-for-dazodalibep-in-moderatetosevere-systemic-sjgrens-disease
- 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; NCT06104124. Updated September 14, 2026. Accessed September 23, 2026. https://clinicaltrials.gov/study/NCT06104124
- 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
