Novel Therapies in Sjögren's Disease: Systematic Review Finds Ianalumab and Telitacicept Lead a New Era of Targeted Treatment
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A comprehensive systematic review published in Best Practice and Research Clinical Rheumatology assessed the landscape of emerging therapies for Sjögren's disease, cataloguing findings from Phase II and Phase III trials through mid-2025. For the first time in the history of the disease, two agents -- the B-cell-depleting antibody ianalumab and the dual BAFF/APRIL inhibitor telitacicept -- demonstrated meaningful, statistically significant reductions in systemic disease activity in Phase III trials. Researchers found that targeting B-cell survival pathways represented the most clinically validated therapeutic strategy to date, with several additional agents including deucravacitinib and dazodalibep under active investigation.
Abstract
Sjögren's disease is a chronic systemic autoimmune condition characterized by lymphocytic infiltration of exocrine glands, leading to dryness of the eyes and mouth, fatigue, and systemic organ involvement in a substantial proportion of patients. Despite affecting an estimated 0.1-0.4% of the population with a strong female predominance, no disease-modifying therapy had been approved as of early 2025. The inability of numerous prior clinical trials to demonstrate efficacy had been attributed partly to patient heterogeneity, suboptimal outcome measure selection, and the mixed involvement of glandular and extra-glandular disease activity. The publication of validated composite endpoints, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), provided more sensitive and standardized tools for Phase III program design.
This systematic review searched PubMed, EMBASE, EBSCO, and ClinicalTrials.gov for Phase II and III clinical trials evaluating biologic and targeted treatments in primary Sjögren's disease published from 2010 to mid-2025. Evidence was organized by mechanism of action and development phase. Studies were evaluated for patient population, primary endpoints, and key efficacy and safety outcomes, with special attention to the two drugs that achieved Phase III success: ianalumab (VAY736), a fully human monoclonal antibody targeting BAFF-R that both depletes B cells and blocks their survival signaling; and telitacicept, a fusion protein that neutralizes both BLyS (BAFF) and APRIL.
Two global Phase III programs reported positive results in 2025, marking the first time any systemic treatment had demonstrated statistically significant improvement in ESSDAI in this disease. The ianalumab NEPTUNUS-1 and NEPTUNUS-2 trials each met their primary endpoints, with monthly subcutaneous ianalumab significantly improving disease activity over 52 weeks across 779 patients. The telitacicept Phase III study in 381 patients with anti-SSA-positive primary Sjögren's disease also met all primary and secondary endpoints, with the 160 mg dose achieving highly significant ESSDAI improvements at weeks 24 and 48. Beyond these agents, Phase II data supported further investigation of deucravacitinib (a TYK2 inhibitor), dazodalibep, nipocalimab, and efgartigimod. The review concludes that targeting B-cell activation and survival is the most robustly validated therapeutic approach in Sjögren's disease, and that the field is at an inflection point after decades of failed trials.