Dazodalibep Lowers Sjögren’s Disease Activity: Ghaith Noaiseh, MD

Dazodalibep, an investigational fusion protein designed to inhibit CD40/CD40 ligand signaling, significantly reduced systemic disease activity versus placebo at week 48 in patients with moderate to severe Sjögren’s disease in the phase 3 OASIZ-301 trial, with a treatment effect emerging as early as week 4.¹ 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, discussed the findings in an interview.

Noaiseh presented the late-breaking results at the ACR Convergence 2026, held November 6-11 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 1:1:1 to intravenous dazodalibep 1500 mg every 4 weeks, 3000 mg every 12 weeks, or placebo.¹˒² Noaiseh said mean baseline ESSDAI was about 10, reflecting extraglandular involvement such as arthritis, lung disease, and lymphadenopathy.

“In the eyes of many physicians, and I would argue even some rheumatologists, Sjögren’s is predominantly dry eye, dry mouth disease, and it clearly is not. It is far more than that. It is a complex, multisystem disease with defined pathobiology and potentially life-threatening complications, including lymphoma,” Noaiseh said.

ESSDAI decreased by a least squares mean of 5.6 points with dazodalibep 1500 mg and 5.2 points with 3000 mg versus 3.8 points with placebo (differences, −1.8 and −1.4; adjusted P < .001 and P = .010, respectively).¹ The 1500 mg regimen also improved patient-reported dryness on the EULAR Sjögren’s Syndrome Patient Reported Index (−2.50 vs −1.33; adjusted P < .001), and adverse event rates were similar across groups.

Noaiseh described Sjögren’s as highly heterogeneous, with fatigue and dryness often driving patient burden while lung or kidney involvement may cause few symptoms, and said the diagnosis is frequently missed. He said the results support CD40/CD40 ligand targeting in a disease he noted still lacks effective FDA-approved therapies. These congress data have not been peer reviewed.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.