Amgen Reports Phase 3 Success for Dazodalibep in Sjögren’s Disease

Amgen reported positive Phase 3 results for dazodalibep in adults with moderate-to-severe systemic Sjögren’s disease, with both tested dosing regimens significantly reducing disease activity compared with placebo at Week 48. The findings from the OASIZ-301 trial support continued development of the investigational CD40 ligand (CD40L) antagonist, although the magnitude of the placebo-adjusted benefit and the available secondary endpoint data remain important considerations when assessing its clinical potential.

Dazodalibep is a potential first-in-class CD40L antagonist fusion protein designed to disrupt interactions between T cells, B cells and other antigen-presenting cells involved in immune activation. The approach targets immune signalling implicated in Sjögren’s disease, a systemic autoimmune condition that can cause dryness, fatigue, pain and organ involvement. No medicines are currently approved by the US Food and Drug Administration specifically for Sjögren’s disease.

OASIZ-301 Demonstrates Improvement in Systemic Disease Activity

OASIZ-301 was a randomized, double-blind, placebo-controlled Phase 3 study evaluating dazodalibep in adults with Sjögren’s disease and moderate-to-severe systemic disease activity, defined by a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score of at least 5. Participants entered the study with a mean ESSDAI score of 10.2. The primary endpoint was the change in ESSDAI score from baseline to Week 48.

Patients received intravenous dazodalibep at 1,500 mg every four weeks, 3,000 mg every 12 weeks, or placebo. At Week 48, the least-squares mean ESSDAI change was −5.6 points with four-weekly dosing and −5.2 points with 12-weekly dosing, compared with −3.8 points with placebo.

The placebo-adjusted differences were −1.8 points for the four-weekly regimen (adjusted p<0.001) and −1.4 points for the 12-weekly regimen (adjusted p=0.010). Treatment effects were observed as early as Week 4.

Both regimens therefore met the primary efficacy objective, including the less frequent dosing schedule. However, the placebo group also experienced a substantial reduction in disease activity. The placebo-adjusted differences provide a more informative measure of the additional benefit associated with dazodalibep than the within-group reductions alone.

Dryness Improvements Reported with Four-Weekly Dosing

Dazodalibep administered every four weeks also improved patient-reported dryness, a key secondary endpoint. The EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) dryness score decreased by 2.50 points, compared with 1.33 points with placebo (adjusted p<0.001).

The Diary for Assessing Sjögren’s Patient Reported Index (DASPRI) dryness score decreased by 1.98 points with dazodalibep, compared with 1.05 points with placebo (adjusted p<0.001).

These findings suggest that the four-weekly regimen may provide benefits beyond the reduction in systemic disease activity. However, the company’s announcement did not report corresponding dryness results for the 12-weekly regimen. Consequently, the available findings do not establish whether the less frequent schedule offers comparable benefits for patient-reported dryness.

The study also evaluated other secondary outcomes, including joint symptoms, fatigue and ESSDAI response. Further numerical results and analyses of individual organ domains will help clarify the breadth and clinical relevance of the treatment effect.

Safety and Tolerability Findings

Treatment-emergent adverse events, serious adverse events and adverse events leading to treatment discontinuation occurred at similar rates across the study groups, according to Amgen.

The company’s September 2026 topline announcement identified nasopharyngitis, urinary tract infection, hypertension and infusion-related reactions among adverse events occurring more frequently with dazodalibep than with placebo. These events were generally mild to moderate. Amgen also reported no imbalance in thromboembolic events or opportunistic infections across treatment groups.

Although these findings provide an initial assessment of tolerability, detailed event rates and longer-term observations remain important for evaluating the treatment’s overall safety profile.

Further Development Will Address Different Disease Presentations

Amgen is developing dazodalibep across two patient populations. OASIZ-301 evaluated patients with moderate-to-severe systemic disease activity, whereas the Phase 3 OASIZ-303 study targets patients with a high symptom burden but low systemic disease activity, including those affected by dryness, fatigue and pain.

OASIZ-303 was expected to complete in the fourth quarter of 2026, according to Amgen’s September announcement. The OASIZ-304 open-label extension is designed to assess longer-term safety and tolerability in eligible participants from both studies.

Overall, OASIZ-301 establishes statistically significant Week 48 improvements in systemic disease activity with both dazodalibep dosing regimens. The reported dryness findings add support for the four-weekly schedule, but further analyses are needed to establish the breadth of benefit, its clinical importance and the durability of treatment effects. The results support continued development without yet establishing how dazodalibep will perform in routine clinical practice.

Reference

Amgen To Present New Data Across Rare and Other Serious Autoimmune Diseases at ACR Convergence 2026, Amgen, 27 October 2026

A Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren’s Syndrome (SS) With Moderate-to-severe Systemic Disease Activity, ClinicalTrials.gov ID NCT06104124