Amgen reports positive Phase 3 data for dazodalibep in Sjögren's disease

Amgen said in a press release that dazodalibep, its investigational CD40 ligand antagonist fusion protein, met the primary endpoint in the Phase 3 OASIZ-301 trial for patients with moderate-to-severe Sjögren's disease. The primary endpoint was change from baseline at 48 weeks on the EULAR Sjögren's Syndrome Disease Activity Index, or ESSDAI.

The release described the study as global, randomized, double-blind and placebo-controlled, enrolling 648 patients with an ESSDAI score of at least 5. Participants were assigned evenly to dazodalibep 1,500 mg every four weeks, dazodalibep 3,000 mg every 12 weeks, or placebo. The mean baseline ESSDAI score was 10.2.

At 48 weeks, patients on the every-four-week dose (217 participants) had a 5.6-point reduction, compared with 3.8 points on placebo, a placebo-adjusted difference of 1.8 points (adjusted p<0.001). The every-12-week dose (217 participants) produced a 5.2-point reduction, a 1.4-point difference (adjusted p=0.010). Amgen reported that the treatment effect appeared by week 4 and continued through the end of the 48-week period.

The every-four-week dose also showed gains over placebo on patient-reported dryness. Compared with placebo, the every-four-week dose improved the ESSPRI dryness domain by 1.17 points and the DASPRI dryness domain by 0.93 points; both results had adjusted p<0.001, according to the company.

Across the 48 weeks, total ESSPRI and DASPRI scores were better in the dazodalibep arms than in the placebo arm. The average total ESSPRI improvement surpassed 1.5 points with both dosing schedules. A greater share of patients on dazodalibep met STAR response criteria and had ESSDAI reductions of at least 3, 5 or 7 points. They also had larger increases in stimulated salivary flow, the announcement said.

The most common adverse events in the dazodalibep groups, each occurring in at least 5% and more often than with placebo, included infusion-related reactions, nasopharyngitis, urinary tract infection and hypertension. Most were mild or moderate. Serious adverse events and treatment discontinuations caused by side effects were similar across the three groups. Amgen said it saw no imbalance in thromboembolic events or opportunistic infections, and malignancy rates were low and comparable.

Amgen's release quoted Jay Bradner, executive vice president for research and development, saying the findings "support dazodalibep's potential as a first-in-class treatment for Sjögren's disease and strengthen the clinical rationale for targeting CD40L-mediated immune signaling." The company noted there are currently no FDA-approved therapies for Sjögren's disease. Full results will be presented in a late-breaker at the American College of Rheumatology Convergence 2026. Amgen is also evaluating dazodalibep in the Phase 3 OASIZ-303 study, for patients whose disease activity is low but whose symptom burden is high, and in OASIZ-304, an open-label extension. The announcement does not constitute regulatory approval.