Sjögren's disease (increasingly designated SjD, reflecting its recognition as a distinct systemic autoimmune disease rather than merely a syndrome) has long lacked any approved systemic targeted therapy — management has meant symptomatic relief and general immunosuppression. That is on the verge of changing, with the field recording its first positive pivotal trials.
Ianalumab: the first positive Phase 3 program
The headline development is ianalumab (VAY736), an antibody with a dual mechanism — B-cell depletion plus BAFF-receptor inhibition. In 2025, its two global Phase 3 trials (NEPTUNUS-1 and NEPTUNUS-2) both met their primary endpoint of improving disease activity (ESSDAI), with benefits on patient-reported burden emerging early. These are the first paired Phase 3 trials in Sjögren's disease to succeed, and ianalumab is now positioned to potentially become the first targeted therapy approved for the condition.
Targeting the CD40–CD40L axis and FcRn
Several other mechanisms have produced positive controlled data. Iscalimab (anti-CD40) improved systemic disease activity and some symptom measures in the Phase 2b TWINSS trial. Dazodalibep (an anti-CD40L agent) met its primary endpoint in a Phase 2 trial across both systemic-disease and symptom-predominant cohorts. Nipocalimab (an FcRn inhibitor) significantly improved disease activity in the Phase 2 DAHLIAS study, and TYK2 inhibition is also under investigation. Collectively these represent the most promising pipeline the disease has ever had.
A realistic view of older biologics
It is worth being candid that earlier B-cell approaches disappointed in controlled trials: rituximab (as in TRACTISS) and abatacept did not clearly improve objective glandular endpoints, and a meta-analysis found no significant benefit of several biologics on salivary flow — though earlier intervention may matter. This context is exactly why the new dual-mechanism and CD40-axis results are significant.
Symptomatic care remains essential: cholinergic agonists (pilocarpine, cevimeline), saliva substitutes and secretagogues for dry mouth, and targeted immunomodulators or regenerative approaches for severe dry eye. Mesenchymal stem cell and CAR-T strategies remain experimental.
| Therapy | Target | Key result | Status |
|---|---|---|---|
| Ianalumab | B-cell depletion + BAFF-R | Two positive Phase 3 trials (NEPTUNUS-1/2) | Potential first approved therapy |
| Iscalimab | CD40 | Positive Phase 2b (TWINSS) | Advancing |
| Dazodalibep | CD40L | Positive Phase 2 | Advancing |
| Nipocalimab | FcRn | Positive Phase 2 (DAHLIAS) | Advancing |
| Rituximab / abatacept | B cells / costimulation | Disappointing on objective endpoints | Not standard |
Further reading: ianalumab NEPTUNUS-1/2 (Novartis, 2025); iscalimab TWINSS (Fisher et al., Lancet 2024); dazodalibep (Nature Medicine 2024); nipocalimab DAHLIAS (Phase 2, 2024).