Breakthrough Therapy Ianalumab Nears FDA Submission for Sjögren, With Thomas Grader-Beck, MD

The FDA has granted Breakthrough Therapy designation to ianalumab for Sjögren disease, marking a major regulatory milestone for a condition that has long lacked targeted, FDA-approved treatments and underscoring the strength of recent phase 3 data.¹

Novartis announced the designation alongside plans to submit regulatory applications in early 2026. If approved, ianalumab would become the first targeted therapy specifically indicated for Sjögren disease, a heterogeneous systemic autoimmune condition associated with significant symptom burden and limited therapeutic options.

Ianalumab is a fully human monoclonal antibody with a dual mechanism, combining antibody-dependent cellular cytotoxicity with blockade of the B-cell activating factor receptor (BAFF-R). The therapy is currently being evaluated in the pivotal phase 3 NEPTUNUS-1 and NEPTUNUS-2 trials, both of which met their primary endpoint of change from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 48 versus placebo.

In NEPTUNUS-1, monthly ianalumab 300 mg led to a greater mean reduction in ESSDAI than placebo (−6.4 vs −5.1), with a least-squares mean difference of −1.3 (95% CI, −2.6 to 0.0; P = .0496). NEPTUNUS-2 similarly demonstrated a significant benefit with monthly dosing (−6.5 vs −5.5; LS mean difference −1.0; 95% CI, −2.0 to 0.0; P = .041), while quarterly dosing did not differ significantly from placebo. In pooled analyses, monthly ianalumab produced greater ESSDAI improvement than placebo (LS mean difference −1.2; 95% CI, −2.0 to −0.4; P = .0031) along with improvements in patient-reported outcomes.²

Rheumatology Live spoke with Thomas Grader-Beck, MD, Associate Professor of Clinical Medicine at Johns Hopkins University of Medicine, an investigator on the NEPTUNUS trials. He emphasized why the Breakthrough Therapy designation is particularly meaningful in Sjögren disease, highlighting how the dual B-cell depletion and BAFF-R blockade strategy may overcome limitations seen with prior approaches and potentially reshape how clinicians and patients approach treatment discussions if approved.

References

1. Novartis ianalumab receives FDA Breakthrough Therapy designation for Sjögren’s disease. News release. Novartis. January 16, 2025. https://www.novartis.com/us-en/news/media-releases/novartis-ianalumab-receives-fda-breakthrough-therapy-designation-sjogrens-disease

2. Johnson V. NEPTUNUS-1 and 2: Monthly Ianalumab Significantly Improves Sjögren Disease Activity. Article. RheumatologyLive. November 4, 2025. https://www.rheum-live.com/view/neptunus-1-2-monthly-ianalumab-significantly-improves-sjogren-disease-activity