AI-generated summaries. Verify every claim with the cited sources before acting on them. Read our methodology

← Back to all reports

Sjögren's Syndrome

Recent research efforts aimed at curing Sjögren's Syndrome.

Last updated

Sjögren’s Syndrome

Overview

Sjögren’s Syndrome, increasingly called Sjögren’s disease, is a chronic autoimmune condition in which the immune system attacks moisture-producing glands, especially the salivary and tear glands. It commonly causes persistent dry mouth and dry eyes, but may also cause fatigue, pain, dental damage, and—in some people—problems involving the lungs, kidneys, nerves, skin, or blood vessels. It affects people of all sexes but is much more common in women. NIAMS overview MedlinePlus Genetics

For many people, prognosis is compatible with a normal lifespan, but disease can be seriously disabling and active systemic disease carries risks including organ damage and lymphoma. MedlinePlus prognosis There is no established cure. Standard care remains symptom-focused—artificial tears, saliva substitutes, dental prevention, and saliva-stimulating drugs such as pilocarpine or cevimeline—with immunosuppressive or biologic treatment reserved for selected patients with important systemic involvement. EULAR management recommendations

Scope of Recent Research (2020–present)

Research activity has accelerated since 2020, particularly around stopping pathogenic B cells, reducing harmful autoantibodies, interrupting T-cell/B-cell signaling, and resetting the immune system with engineered cell therapies. Several randomized trials have now shown reductions in systemic disease activity, but these are disease-controlling approaches rather than demonstrated cures; the field is not yet able to reliably restore immune tolerance or regenerate damaged glands in people. Dazodalibep phase 2 trial Ianalumab Phase III results

Major Breakthroughs and Emerging Therapies

The strongest recent progress is in targeted immune therapies directed at B cells and their supporting signals. Ianalumab is an antibody designed both to deplete B cells and block BAFF-R, a receptor that helps B cells survive. In 2025, sponsor Novartis reported that both global Phase III NEPTUNUS trials met their primary endpoint of improving systemic disease activity. Ianalumab Phase III results Iscalimab, which blocks the CD40–CD40 ligand costimulatory pathway used by immune cells to activate one another, produced statistically significant improvements in the clinician-scored disease-activity index at two doses in a Phase IIb trial, although patient-reported symptom improvement did not reach statistical significance in the high-symptom cohort. TWINSS iscalimab Phase IIb trial

Another promising strategy targets autoantibodies directly. Nipocalimab blocks the neonatal Fc receptor, or FcRn, which normally protects immunoglobulin G (IgG) antibodies from breakdown; blocking FcRn lowers circulating IgG, including disease-associated anti-Ro/SSA and anti-La/SSB antibodies. In the randomized Phase II DAHLIAS study, the 15 mg/kg dose improved clinician-assessed disease activity at 24 weeks versus placebo, supporting the ongoing Phase III program. DAHLIAS nipocalimab Phase II trial This approach may suppress a major driver of disease without permanently eliminating antibody-producing cells, but it has not shown that established gland damage can be reversed. DAHLIAS nipocalimab Phase II trial

Dazodalibep is an investigational CD40-ligand antagonist intended to disrupt communication between activated T cells and B cells. In a randomized Phase II trial, it significantly improved systemic disease activity in participants with moderate-to-severe systemic Sjögren’s disease and improved a composite symptom endpoint in a separate high-symptom population. Dazodalibep phase 2 trial This is important because Sjögren’s has long had a record of negative trials despite biologically plausible therapies; dazodalibep is now being tested in larger Phase III studies. OASIZ-301 trial OASIZ-303 trial

The most explicitly “curative” experimental concept is immune reset through chimeric antigen receptor T-cell therapy, or CAR-T. These are a patient’s T cells engineered to eliminate selected immune-cell populations; CD19 targets B cells, while BCMA targets antibody-secreting plasma cells. A 2022 report embedded within a BCMA CAR-T study described two people with Sjögren’s disease who had reduced anti-SSA antibodies, improved disease scores, and improved salivary and tear measures 12 weeks after infusion. BCMA CAR-T study including Sjögren’s patients Dedicated early-stage trials of CD19/BCMA-directed CAR-T for refractory Sjögren’s are under way, but the available evidence remains extremely small and short-term. CD19/BCMA CAR-T Sjögren’s trial

Regenerative research is also advancing, although it remains preclinical or platform-stage rather than a treatment proven in Sjögren’s. Researchers are developing human salivary-gland organoids—miniature gland-like tissues grown in the laboratory—to study disease and potentially replace or repair damaged secretory tissue. A recent human-organoid study reported preservation of multiple salivary epithelial cell types and gland-like reconstruction after transplantation into an animal model. Human salivary-gland organoids A realistic cure may ultimately require both durable immune tolerance and recovery of gland function.

Clinical Trials and Experimental Approaches

Ianalumab has generated the most advanced disease-modifying evidence. NEPTUNUS-1 enrolled 275 participants and NEPTUNUS-2 enrolled 504 participants in randomized, placebo-controlled Phase III studies of subcutaneous ianalumab for active disease. NEPTUNUS-1 trial record NEPTUNUS-2 trial record Novartis reported statistically significant reductions in ESSDAI, a clinician-scored index of systemic disease activity, in both trials; the studies and their extension continue to characterize long-term benefit and safety. Ianalumab Phase III results

Janssen’s nipocalimab is in the randomized, placebo-controlled Phase III DAFFODIL trial for moderate-to-severe Sjögren’s disease following positive Phase II findings. DAFFODIL Phase III trial Amgen is conducting the Phase III OASIZ-301 study in participants with systemic disease activity and OASIZ-303 in people with a moderate-to-severe symptom state; both follow the positive Phase II dazodalibep study. OASIZ-301 trial OASIZ-303 trial A long-term extension will follow participants from the two pivotal dazodalibep studies for an additional 132 weeks of treatment. Dazodalibep extension study

Cell therapy is earlier. The dedicated CD19/BCMA CAR-T trial for refractory Sjögren’s is an early-phase, single-arm study focused on safety, dose-limiting toxicity, and preliminary efficacy rather than proof of cure. CD19/BCMA CAR-T Sjögren’s trial These studies are especially notable because they aim to remove both B cells and long-lived plasma-cell compartments that conventional B-cell depletion may leave behind. BCMA CAR-T study including Sjögren’s patients

Methodologies and Scientific Approaches

Researchers increasingly combine blood tests, minor salivary-gland biopsies, imaging, and validated clinical outcome measures to divide Sjögren’s into biologically distinct subgroups. Trials commonly use ESSDAI for systemic disease, while patient-reported measures capture dryness, pain, and fatigue; discordance between these measures is a major reason why a drug can appear effective in one outcome but not another. TWINSS iscalimab Phase IIb trial Sjögren’s Foundation treatment-response project

Single-cell RNA sequencing, spatial transcriptomics, and spatial metabolomics are being used to map which immune and glandular cells are abnormal and where they are located within salivary tissue. Spatial multi-omics study In parallel, Sjögren-prone mouse models, patient-derived serum experiments, and human organoids allow investigators to test immune targets and gland-repair strategies before exposing patients to experimental treatments. Sjögren’s Foundation research programs Human salivary-gland organoids

Leading Institutions and Funding

Large multicenter trials are being driven by industry sponsors with global rheumatology networks: Novartis sponsors ianalumab’s NEPTUNUS program, Janssen sponsors nipocalimab’s DAFFODIL program, and Amgen sponsors the OASIZ dazodalibep studies. NEPTUNUS-1 trial record DAFFODIL Phase III trial OASIZ-301 trial Academic investigators and hospital systems remain essential for recruitment, biopsy-based translational studies, and long-term follow-up.

The Sjögren’s Foundation is an important U.S. research funder and convening organization. Its 2024 grant program awarded one High Impact Grant, three Pilot Grants, and one Dynamic Grant, supporting work at institutions including the Oklahoma Medical Research Foundation, UCLA, Northeastern University, the National Institute of Dental and Craniofacial Research, Baylor College of Medicine, Johns Hopkins University, the University of Pittsburgh, and the University of Missouri. Sjögren’s Foundation 2024 grant awardees

Strengths, Limitations, and Challenges

The field’s main strength is that it now has multiple therapies with positive randomized-trial signals across distinct immune mechanisms: B-cell depletion/BAFF-R blockade, CD40 pathway blockade, FcRn inhibition, and CD40-ligand blockade. Ianalumab Phase III results TWINSS iscalimab Phase IIb trial Dazodalibep phase 2 trial The major limitation is heterogeneity: some patients have mainly dryness and fatigue, while others have systemic inflammatory disease, and a treatment that improves one group or outcome may not help another. Sjögren’s Foundation treatment-response project

None of the advanced drugs has yet established lasting drug-free remission, regeneration of severely damaged glands, or prevention of all complications. CAR-T is scientifically compelling but currently rests on very small Sjögren’s datasets and entails substantial practical and safety questions, including the need for specialized centers, immune suppression around treatment, infection monitoring, and long-term surveillance. BCMA CAR-T study including Sjögren’s patients CD19/BCMA CAR-T Sjögren’s trial

Outlook and Future Directions

As of August 8, 2026, Sjögren’s research is closer to its first broadly validated disease-modifying treatments than to a proven cure. The most important near-term milestones are peer-reviewed full results and regulatory decisions for ianalumab, Phase III readouts for nipocalimab and dazodalibep, and durable follow-up from CAR-T studies. Ianalumab Phase III results DAFFODIL Phase III trial Dazodalibep extension study A true cure will likely require evidence that immune tolerance can be restored long term and that lost salivary and tear-gland function can be preserved or rebuilt.

References

Don't see your disease? Request a report