Amgen: Dazodalibep met Phase 3 primary endpoint in moderate-to-severe Sjögren's disease

Topline efficacy

The Phase 3 OASIZ 301 study met its primary endpoint, showing a statistically significant and clinically meaningful improvement in systemic disease activity as measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 48. Improvements were observed as early as Week 4 and were sustained through Week 48.

Study design

OASIZ 301 was a randomized, double-blind, placebo-controlled Phase 3 study in patients with moderate-to-severe systemic Sjögren's disease (ESSDAI ≥ 5), enrolling approximately 621 participants. 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 (a decrease of at least 5 points from baseline).

Safety

The most common adverse events (≥5% incidence and reported at higher rates with dazodalibep versus placebo) were nasopharyngitis, urinary tract infection, hypertension and infusion-related reactions, generally mild to moderate. Discontinuations due to adverse events occurred at a low rate and were balanced across treatment groups. No imbalance in thromboembolic events or opportunistic infections was observed across arms.

Mechanism and next steps

Dazodalibep is a potential first-in-class CD40L antagonist fusion protein intended to disrupt interactions between T cells, B cells and antigen-presenting cells. Amgen plans to present detailed OASIZ 301 data at a medical meeting. The Phase 3 OASIZ 303 study (high symptom burden with low systemic activity) is expected to complete in Q4 2026, and OASIZ 304 is an open-label long-term extension for eligible participants.