Sjogren's Disease: An Evolving Treatment Landscape
Sjögren's disease (SjD) is a systemic autoimmune disorder primarily affecting the exocrine glands, causing dry eyes and dry mouth. Many patients also experience systemic symptoms and potential organ damage. Despite being common, especially in women, effective systemic treatments have been limited, with focus primarily on symptom relief.
A new era of targeted therapies is emerging from clinical trials, aiming to treat the root causes of SjD rather than just symptoms.
The Rise of Nipocalimab
Nipocalimab, an investigational monoclonal antibody from Johnson & Johnson, is a significant development. It received Breakthrough Therapy and Fast Track designations from the FDA for moderate-to-severe SjD in late 2024 and early 2025.
Mechanism of Action
Nipocalimab is an FcRn blocker that reduces levels of circulating IgG antibodies, including those driving SjD, by promoting their degradation.
Promising Phase 2 Results
The Phase 2 DAHLIAS study (NCT04968912) showed nipocalimab significantly improved the ClinESSDAI score in patients compared to placebo. A Phase 3 study is ongoing.
Ianalumab: A Dual-Action B-Cell Inhibitor
Novartis's ianalumab (VAY736) is another promising treatment. It recently reported positive top-line results from its global Phase 3 NEPTUNUS-1 and NEPTUNUS-2 trials in August 2025.
Mechanism of Action
Ianalumab targets B-cells in two ways: depleting them through ADCC and inhibiting the BAFF-R, disrupting their survival signals. This targeted approach aims to be more effective than older B-cell therapies.
Phase 3 Trial Success
The NEPTUNUS trials in patients with active extraglandular disease met the primary endpoint of significantly improved disease activity. These are the first global Phase 3 trials to show this for a targeted SjD treatment. Novartis plans to seek global approval.
Other Emerging Therapies
Beyond nipocalimab and ianalumab, other promising treatments are in development.
Dazodalibep
- Mechanism: A CD40L antagonist, it blocks the interaction between CD40 and CD40L essential for B-cell and T-cell activation in autoimmune diseases.
- Clinical Status: Phase 2 results showed improvements in disease activity and symptoms. Phase 3 trials are planned.
Telitacicept
- Mechanism: This fusion protein (TACI-Fc) targets BAFF and APRIL, which are elevated in SjD.
- Clinical Status: A Phase 2 trial reduced ESSDAI score. A Phase 3 trial is ongoing.
Autologous Stem Cell Therapy
- Mechanism: Researchers are using a patient's own bone marrow stem cells to potentially regenerate salivary gland function and treat dry mouth.
- Clinical Status: A Phase 1 safety trial treated its first patient in early 2025.
Neurostimulation
- Mechanism: Electrical stimulation targets nerves controlling tear and saliva production to alleviate dry eye and mouth.
- Clinical Status: Early studies are assessing this method.
Comparison of Key Emerging Sjogren's Disease Treatments
| Feature | Nipocalimab | Ianalumab | Dazodalibep |
|---|---|---|---|
| Developer | Johnson & Johnson | Novartis | Horizon Therapeutics (now Amgen) |
| Mechanism | FcRn blocker (reduces IgG antibodies) | Dual-action B-cell inhibitor (depletes B-cells and inhibits BAFF-R) | CD40L antagonist (blocks T-cell/B-cell interaction) |
| Clinical Status | Positive Phase 2; Phase 3 ongoing; FDA Breakthrough and Fast Track designations (Nov 2024/Mar 2025) | Positive Phase 3 top-line results (Aug 2025); Submissions to health authorities planned | Positive Phase 2; Phase 3 planned |
| Primary Target | Autoantibodies (IgG) | B-cells | CD40-CD40L pathway |
| Administration | Intravenous (in trials) | Monthly or tri-monthly (in trials) | Not specified in search results |
A Promising Future for Sjogren's Patients
The development of targeted therapies like nipocalimab and ianalumab is a significant step for Sjögren's disease patients. These investigational treatments and other approaches like cellular therapy and neurostimulation represent a shift towards addressing the underlying immune dysfunction.
Positive clinical trial data indicates potential for more effective disease control and improved quality of life. Ongoing research and new techniques are paving the way for personalized medicine in Sjögren's disease.
For information on clinical trials, visit ClinicalTrials.gov.
Conclusion
The pipeline for Sjögren's disease treatments is promising. Nipocalimab and ianalumab, advancing through clinical trials, offer hope for the first approved therapies targeting the disease's cause. These developments suggest a future with more effective treatments, better symptom control, and improved outcomes for patients.
