Understanding NEPTUNUS Trials and Ianalumab’s Mechanism

Replicated phase 3 success has arrived for Sjögren’s disease, with ianalumab reducing systemic disease activity across 2 global trials, though the size of the effect tempers expectations.

In this Special Report series, Nehad Soloman, MD, FACR, of Arizona Arthritis and Rheumatology Associates, spoke with Teja Kapoor, MD, director of the Columbia Sjögren’s Center, about the NEPTUNUS-1 and NEPTUNUS-2 results.

Both 52-week, randomized, double-blind, placebo-controlled trials met their primary end point, change in ESSDAI score. With monthly dosing, ianalumab outperformed placebo by roughly 1 to 1.3 ESSDAI points, while the every-3-month regimen showed little separation.¹

The ESSDAI spans 12 domains, including lymphadenopathy, constitutional, articular, and neurologic involvement.² Its emphasis on systemic features, rather than dryness, defines the population in which benefit was measured. Results presented at the International Sjögren’s Symposium showed response on the STAR composite index in about 57% to 59% of patients on monthly ianalumab vs about 40% on placebo.

Ianalumab acts through 2 pathways. It depletes B cells through antibody-dependent cellular cytotoxicity and blocks the B-cell activating factor receptor (BAFF-R), which supports B-cell survival and activation.¹

This mechanism points toward patients with heavy B-cell activity, including those with hypergammaglobulinemia, glandular disease, cytopenias, or low complement levels. The consistency of results across trials and end points strengthens the case for B-cell targeting in systemic Sjögren’s disease.

References

1. Mariette X, Grader-Beck T, Finzel S, et al. Ianalumab for the treatment of patients with Sjögren’s disease. N Engl J Med. 2026;395(16):1585-1599. doi:10.1056/NEJMoa2601088

2. Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis. 2010;69(6):1103-1109. doi:10.1136/ard.2009.110619