Dazodalibep Dual-Domain Win Meets First-in-Disease Payer and Safety Test

Amgen's Dazodalibep Phase 3 OASIZ-301 Study Shows Significant Sjögren's Disease Improvement

Amgen announced new data presentations at ACR Convergence 2026, highlighting its portfolio in rare and autoimmune diseases. Key findings from the Phase 3 OASIZ-301 study of dazodalibep in Sjögren's disease showed statistically significant and clinically meaningful reductions in systemic disease activity and patient-reported dryness. Patients receiving dazodalibep every four weeks experienced a -5.6 point reduction in ESSDAI score (difference vs placebo, -1.8; adjusted p<0.001), and those on the every 12-week regimen saw a -5.2 point reduction (difference vs placebo, -1.4; adjusted p=0.010). Significant improvements in dryness were also observed, with ESSPRI and DASPRI scores showing reductions (adjusted p<0.001). The company also presented long-term UPLIZNA data in IgG4-Related Disease and real-world evidence for KRYSTEXXA and TAVNEOS in uncontrolled gout and ANCA-associated vasculitis, respectively.

• The Phase 3 OASIZ-301 study demonstrated that dazodalibep significantly reduced systemic disease activity in Sjögren's disease patients. Both dosing regimens, 1,500 mg every four weeks and 3,000 mg every 12 weeks, led to statistically significant and clinically meaningful improvements in the European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index (ESSDAI) score compared to placebo, with effects observed as early as four weeks.
• Beyond systemic activity, dazodalibep (1,500 mg every four weeks) also showed statistically significant and clinically meaningful improvements in patient-reported dryness, a key secondary endpoint. Patients reported greater reductions in dryness as measured by both the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and the Diary for Assessing Sjögren's Patient Reported Index (DASPRI) dryness scores, addressing a critical symptomatic burden for patients.
• The safety profile of dazodalibep in the OASIZ-301 study was comparable across treatment groups, with similar rates of treatment-emergent adverse events, serious adverse events, and discontinuations. These positive results are particularly encouraging given that there are currently no FDA-approved medicines specifically for Sjögren's disease, highlighting dazodalibep's potential to address a significant unmet medical need for patients.
• Amgen's presence at ACR Convergence 2026 extended beyond dazodalibep, including presentations on UPLIZNA for IgG4-Related Disease (long-term safety and efficacy from MITIGATE open-label extension), and real-world evidence for KRYSTEXXA in uncontrolled gout and TAVNEOS in ANCA-associated vasculitis. This demonstrates Amgen's broad commitment to advancing therapies and understanding medicines across various rare and serious autoimmune conditions.

The Significant Unmet Need in Sjögren's Disease Treatment

No disease-modifying therapy is currently approved for Sjögren's disease, and no immunomodulatory drug has been approved for primary Sjögren's syndrome. Management remains largely symptomatic, centered on artificial tears, sialogogues, and hydroxychloroquine, none of which reliably arrest systemic immunopathology.

• Symptomatic therapies do not modify disease course: Treatment of sicca manifestations is symptomatic and is based on saliva substitutes and preservative-free artificial tears, with stimulation of salivary flow with a sialogogue (pilocarpine or cevimeline) for patients with residual salivary gland function, while conventional therapy including moisturizers, pilocarpine, cevimeline, local cyclosporine, and hydroxychloroquine remains the basis for treatment but does not modify the course of the disease.

• No evidence-based guidelines and low level of evidence: No evidence-based therapeutic guidelines are currently available, and the overall low level of evidence in therapeutic studies suggests that much larger trials of the most promising therapies are necessary.

• Limited efficacy of systemic and biologic agents in controlled trials: RCTs have demonstrated the lack of efficacy of antitumor necrosis factor agents, with two placebo-controlled trials of infliximab and etanercept not achieving the primary outcome, while the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo, and randomised clinical trials of rituximab have failed to demonstrate consistent efficacy.

• Systemic immunosuppression reserved for severe disease without controlled guidance and with safety burden: Systemic treatment is reserved for systemic manifestations, with glucocorticoids and immunosuppressive agents reserved for severe systemic involvement although no controlled trials guide their use, and infection remains the primary complication, emphasizing the need to balance benefits of immunosuppressive therapy and the risk of infection.

• Diagnostic delay and persistent unmet symptom burden: Patients experience a diagnostic delay averaging roughly five to six years from symptom onset, during which irreversible glandular and systemic damage may accumulate, with persistent burden of fatigue, cognitive dysfunction, chronic pain, and lymphoproliferative risk, and development of malignant B cell lymphoma affecting about 5% of primary SS patients.

Dazodalibep's Phase 3 OASIZ-301 Design and Key Endpoints

Recent randomized trials in Sjögren's disease evaluate both symptomatic stimulants and systemic immunomodulators across diverse populations. Designs are predominantly randomized, double-blind, placebo-controlled studies with primary endpoints anchored on ESSDAI, ESSPRI, glandular function measures and composite response criteria.

Dazodalibep's CD40L MoA: Broader Potential in Autoimmune Diseases

Dazodalibep, a non-antibody biological antagonist of CD40L and Fc-free albumin-fusion CD154 antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, has been trialled beyond Sjögren's disease in rheumatoid arthritis and in kidney transplantation for rejection prophylaxis. In rheumatoid arthritis the MIDORA trial evaluated four different dosing regimens versus placebo, while in kidney transplantation dazodalibep was administered with belatacept in a single-arm phase 2a trial.

• Rheumatoid arthritis — MIDORA intervention model: The MIDORA trial was a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study in adult patients with moderate-to-severe active RA with a positive test for serum rheumatoid factor and/or anticitrullinated protein antibodies, an inadequate response to methotrexate, other conventional disease-modifying antirheumatic drugs or tumour necrosis factor-α inhibitors, and no prior treatment with B-cell depleting agents. Eligible participants were randomised equally to five groups receiving intravenous infusions of DAZ or placebo, with the primary endpoint of change from baseline in Disease Activity Score-28 with C reactive protein (DAS28-CRP) at day 113 and follow-up through day 309 (NCT04163991).

• Rheumatoid arthritis — efficacy and safety: The study randomised 78 eligible participants. The change from baseline in DAS28-CRP (least squares means±SE) at day 113 was significantly greater for all DAZ groups (-1.83±0.28 to -1.90±0.27; p<0.05) relative to PBO (-1.06±0.26), with significant reductions in DAS28-CRP also observed for all DAZ groups at day 309. The distribution of adverse events was balanced among DAZ and PBO groups (74% and 63%, respectively), with four serious adverse events deemed by investigators to be unrelated to study medication.

• Kidney transplantation — rejection prophylaxis intervention model: Dazodalibep, an Fc-free albumin-fusion CD154 antagonist, was administered with belatacept to kidney transplant recipients in a single-arm phase 2a trial without thrombotic events, but the prespecified composite efficacy endpoint was not met.