Dazodalibep Eases Sjögren’s Dryness via CD40L Blockade: Ghaith Noaiseh, MD

Dazodalibep improved patient-reported dryness as well as systemic disease activity in the phase 3 OASIZ-301 trial in Sjögren’s disease, and Ghaith Noaiseh, MD, associate professor of allergy, clinical immunology, and rheumatology at the University of Kansas Medical Center and director of the KU Sjögren’s Center, said its CD40 ligand-blocking mechanism acts on several drivers of the disease.¹

Noaiseh presented the late-breaking results at the ACR Convergence 2026, held November 6-11, 2026, in Orlando, Florida. OASIZ-301 (NCT06104124) randomized 648 adults meeting 2016 ACR/EULAR classification criteria with a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) of 5 or greater to intravenous dazodalibep 1500 mg every 4 weeks, 3000 mg every 12 weeks, or placebo, and both doses met the primary ESSDAI endpoint at week 48.¹˒²

“Dazodalibep targets the CD40 ligand molecule, which plays an important role in interrupting the interaction, what we call the crosstalk or handshake between the T and B cell. And this is an important milestone in the inflammatory pathway in Sjögren’s disease,” Noaiseh said.

Blocking CD40 ligand is intended to curb downstream B-cell hyperactivity, autoantibody formation, elevated serum IgG, and immune complex-mediated tissue damage, Noaiseh said. He added it may also limit tertiary lymphoid structure formation and epithelial cell activation within the salivary glands.

With dazodalibep 1500 mg, the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) dryness score improved by 2.50 points versus 1.33 with placebo, and the DASPRI dryness score improved by 1.98 versus 1.05 points (both adjusted P < .001).¹ Noaiseh said the testing hierarchy stopped at swollen and tender joint counts, so later endpoints, including an overall score he said improved numerically with the 1500 mg dose, can be described only as nominal.

Adverse event rates were similar across groups, and Noaiseh said thrombotic and cardiovascular events, a key concern with CD40 ligand targeting, were comparable between arms.¹ He noted a small increase in mostly grade 1 or 2 hypertensive events with dazodalibep. These congress data have not been peer reviewed.

Relevant disclosures include Amgen, Argenx, Bristol-Myers Squibb, Janssen, Johnson & Johnson, MedImmune, Novartis, Roche, Sanofi, UCB, and Vor Bio.

References

1. Noaiseh G, Devauchelle-Pensec V, St Clair EW, et al. Dazodalibep significantly reduces systemic disease activity in patients with Sjögren’s disease and moderate-to-severe disease activity: results from the phase 3 OASIZ-301 trial. Abstract LB22. Presented at: ACR Convergence 2026; November 6-11, 2026; Orlando, FL.

2. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45.