Amgen’s Dazodalibep Reduces Systemic Disease Activity in Phase 3 Sjögren’s Trial

Amgen’s dazodalibep, a CD40 ligand (CD40L) antagonist fusion protein, significantly reduced systemic disease activity compared with placebo at Week 48 in the Phase 3 OASIZ-301 trial in patients with Sjögren’s disease, with both dosing regimens meeting the primary endpoint.¹ The full results, which build on topline data Amgen announced in September, will be presented in a late-breaking session at the American College of Rheumatology (ACR) Convergence 2026.¹

“These phase 3 results support dazodalibep’s potential as a first-in-class treatment for Sjögren’s disease and strengthen the clinical rationale for targeting CD40L-mediated immune signaling in these patients,” said Jay Bradner, MD, executive vice president of research and development, artificial intelligence and data at Amgen.¹

How does dazodalibep work?

Dazodalibep is designed to target immune activation by disrupting interactions between T cells, glandular epithelial cells, B cells, and other antigen-presenting cells.¹ The CD40/CD40L pathway has long been an immunology target, but early trials of CD40L-targeting monoclonal antibodies were halted because of platelet-related thromboembolic complications.³ Dazodalibep, previously known as VIB4920, takes a different approach: it is a bivalent, CD40L-specific Tn3 fusion protein that did not cause platelet aggregation in laboratory studies.³ In OASIZ-301, there was no imbalance in thromboembolic events across treatment groups.¹

Because dazodalibep acts on several cell types involved in the disease, it reflects a broader interest in therapies that hit multiple immune pathways at once. In a BioPharm International® video interview at BIO 2026, Howard Berman, PhD, chief executive officer of ReAlta Life Sciences, said, “Being able to hit all these targets at once is so critically and verifiably important to ameliorate the disease.”

What did OASIZ-301 show?

The randomized, double-blind, placebo-controlled trial enrolled 648 patients with moderate-to-severe systemic disease activity, defined as a score of at least 5 on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI).¹ Patients had a mean baseline ESSDAI score of 10.2.¹

At Week 48, dazodalibep 1,500 mg every four weeks reduced ESSDAI by 5.6 points from baseline compared with 3.8 points for placebo, a difference of 1.8 points (adjusted P<.001).¹ The 3,000 mg every 12 weeks regimen reduced ESSDAI by 5.2 points, a difference of 1.4 points from placebo (adjusted P=.010).¹ A treatment effect was observed as early as Week 4 and was sustained through Week 48.¹

The every-four-weeks regimen also significantly improved patient-reported dryness compared with placebo, with placebo-adjusted differences of −1.17 points on the dryness domain of the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and −0.93 points on the dryness domain of the Diary for Assessing Sjögren’s Patient Reported Index (adjusted P<.001 for both).¹ Patients receiving dazodalibep also showed greater increases in stimulated salivary flow, an objective measure of oral dryness.¹

The results are consistent with a phase 2 trial published in Nature Medicine in 2024, in which dazodalibep reduced ESSDAI by 6.3 points compared with 4.1 points for placebo at Day 169 in 74 patients with moderate-to-severe systemic disease.²

The most common adverse events reported more often with dazodalibep than placebo were nasopharyngitis, urinary tract infection, hypertension, and infusion-related reactions, which were generally mild to moderate.¹ Serious adverse events and discontinuations because of adverse events were balanced across groups, and malignancy rates were low and comparable.¹

Why does Sjögren’s disease need new treatments?

Sjögren’s disease is the second most common autoimmune rheumatic disease, but there are no FDA-approved therapies for it.¹ An estimated 0.25% of the global population is affected, and about half of cases may go undiagnosed.⁴ Management has relied largely on symptomatic relief and off-label immunomodulators.⁴

“Sjögren’s disease is complex and heterogeneous,” said Ghaith Noaiseh, MD, associate professor of medicine at the University of Kansas Medical Center and lead investigator of the study.¹

Competition is building. In January 2026, FDA granted Breakthrough Therapy designation to Novartis’ ianalumab, a monoclonal antibody targeting the BAFF receptor, based on its Phase 3 NEPTUNUS program.⁴

What happens next?

Amgen is also conducting OASIZ-303, a phase 3 study in patients with high symptom burden and low systemic disease activity, and OASIZ-304, an open-label, long-term extension study.¹ “We look forward to building on these findings as we advance a broader Phase 3 program,” Bradner said.¹

References

1. Amgen announces positive Phase 3 results for dazodalibep in Sjögren’s disease. News release. Amgen; November 11, 2026. Accessed November 11, 2026.
2. 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
3. Onuora S. Engineered fusion protein disrupts CD40 signalling. Nat Rev Rheumatol. 2019;15(7):385. doi:10.1038/s41584-019-0252-4
4. Safi MQ, Hussain MD, Chaity NJ. A new horizon for Sjögren’s disease: the FDA breakthrough designation of ianalumab. Ann Med Surg (Lond). 2026;88(5):3018-3019. doi:10.1097/MS9.0000000000004881