Sjögren's disease drug dazodalibep clears its first Phase III hurdle

A new drug for Sjögren's disease is looking like a strong approval candidate after clearing its first Phase III trial. Dazodalibep, an investigational CD40L antagonist developed by Amgen, significantly reduced disease activity in patients with moderate-to-severe Sjögren's disease over 48 weeks — outperforming placebo on the primary outcome measure (ESSDAI) and showing meaningful improvements in patient-reported dryness symptoms.

What makes dazodalibep stand out is both its mechanism and its safety record. Unlike previous CD40L-targeting antibodies that caused dangerous blood clots, dazodalibep is an antibody-based fusion protein with the Fc portion removed — sidestepping that thrombosis risk. Notably, serious adverse events were actually less common in the drug groups than in the placebo group. A second Phase III trial is nearly complete, and if results hold, approval looks likely.

By the Numbers:

• 648 patients enrolled; mean age 53; 94% women
• ESSDAI score reductions: –5.2 (low dose) and –5.6 (high dose) vs. –3.8 with placebo
• ~Two-thirds of patients on dazodalibep achieved a clinically significant 3-point ESSDAI reduction
• Only 5 serious adverse events across the entire study; 2 were in the placebo group

Why it matters: Sjögren's disease has no approved disease-modifying therapies, leaving millions of patients — mostly women — with limited options beyond symptom management. Dazodalibep could be the first drug to meaningfully change that.