Ianalumab significantly improved disease activity and symptoms in patients Sjögren’s disease, phase 3 trials show
Presenter: Thomas Grader-Beck, MD, Johns Hopkins Sjögren’s Center, Baltimore, MD
Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren’s disease: efficacy and safety results from two global phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2). Abstract LB24. Presented October 29, 2025.
A novel, dual-targeted therapy has achieved a key efficacy goal in 2 pivotal phase 3 trials in Sjögren’s disease, setting a milestone in drug development, a researcher said at ACR Convergence 2025.
NEPTUNUS-1 and NEPTUNUS-2 are the first paired phase 3 studies in Sjögren’s disease to meet their primary objective of improvement in disease activity, said Thomas Grader-Beck, MD, of Johns Hopkins Sjögren’s Center in Baltimore, MD.
The replicate studies demonstrated a statistically significant improvement in patients’ scores on the European Alliance of Associations for Rheumatology Sjögren’s syndrome disease activity index (ESSDAI) with ianalumab, a dual-action, B cell-targeted monoclonal antibody.
Treatment also improved symptoms and other measures of disease activity as reported by patients and assessed by physicians in the study, according to Dr. Grader-Beck.
“Ianalumab provided a clinically meaningful benefit to patients, as evidenced by significant improvements in disease activity and reductions in patient burden,” Dr. Grader-Beck said in a podium presentation of the results.
When given once monthly at 300 mg, ianalumab led to a rapid and sustained reduction in disease activity compared with placebo. Ianalumab also demonstrated favorable safety, contributing to a “positive benefit-risk profile,” he said.
The results support continued development of this B cell-targeted agent in Sjögren’s disease, a systemic and heterogeneous autoimmune disease with high unmet treatment needs and no approved systemic therapies.
By binding to the B cell activating factor (BAFF) receptor, ianalumab exhibits a dual mechanism of action.
According to Dr. Grader-Beck, it rapidly depletes B cells through enhanced antibody-dependent cellular cytotoxicity, and also inhibits B cell activation and survival via BAFF receptor blockade.
“B cell hyperactivity and dysregulated BAFF/BAFF-receptor signaling are hallmarks of Sjögren’s disease pathogenesis,” the researcher said.
In the phase 3 NEPTUNUS-1 and NEPTUNUS-2 trials, a total of 779 adult patients with Sjögren’s disease were randomized to receive subcutaneous injections of ianalumab or placebo monthly or every 3 months for 52 weeks.
The primary endpoint was the change in the ESSDAI score from baseline to week 48.
Both studies met this primary objective, both individually and in a pooled data analysis.
The reduction in disease activity was rapid and sustained in comparison to placebo, according to the investigator.
At week 48, the mean ESSDAI score had dropped by 6.5 points in patients receiving ianalumab 300 mg monthly, vs 5.3 points with placebo (P = .0031), according to results of the pooled analysis.
Patients who received ianalumab 300 mg monthly also rated their condition as more improved than those who received placebo. The difference was significant as early as week 8 in the pooled analysis, and up to week 52, the investigator said. The monthly treatment also led to consistently greater improvement than with placebo as assessed by the physician at week 48.
Changes in function were also reported, including salivary flow, which improved for patients receiving ianalumab who had a baseline stimulated salivary flow rate of 0.4 mL/min or greater. In a post hoc analysis, patients above that baseline flow rate cutoff also had less oral dryness with ianalumab than with placebo.
Ianalumab had a favorable safety profile in both studies, according to Dr. Grader-Beck.
The incidence of adverse events was reported to be similar to that with placebo, with very few serious adverse events reported, he said. The incidence of infections was also similar between the placebo and treatment groups.
Disclosures
Thomas Grader-Beck, MD, reported disclosures related to Novartis (advisor or review panel member; consultant).
References
Grader-Beck T, Mariette X, Finzel S, et al. Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren’s disease: efficacy and safety results from two global phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2) [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/ianalumab-demonstrates-significant-reduction-in-disease-activity-in-patients-with-sjogrens-disease-efficacy-and-safety-results-from-two-global-phase-3-randomized-placebo-controlled-double-blind-s/. Accessed October 30, 2025.