Breakthrough Therapy Ianalumab Efficacious, Safe for Sjögren, With Thomas Grader-Beck, MD

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to ianalumab for the treatment of Sjögren disease, a decision supported by consistent phase 3 efficacy signals and a favorable safety profile in a disease area with no approved targeted therapies.¹

The designation follows positive results from the pivotal NEPTUNUS-1 and NEPTUNUS-2 trials, in which ianalumab demonstrated statistically significant improvements in disease activity compared with placebo at 48 weeks. Novartis announced that regulatory submissions are planned for early 2026. If approved, ianalumab would be the first targeted therapy specifically indicated for Sjögren disease.

Ianalumab is a fully human monoclonal antibody that combines antibody-dependent cellular cytotoxicity with blockade of the B-cell activating factor receptor (BAFF-R), a dual mechanism designed to both deplete B cells and inhibit their survival. This strategy addresses limitations observed with prior B-cell–directed approaches that targeted depletion or BAFF signaling alone.

In the phase 3 NEPTUNUS-1 trial, monthly ianalumab 300 mg produced a greater mean reduction from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 48 than placebo (−6.4 vs −5.1), yielding a least-squares (LS) mean difference of −1.3 (95% CI, −2.6 to 0.0; P = .0496). Similar findings were observed in NEPTUNUS-2, where monthly dosing resulted in a greater ESSDAI reduction compared with placebo (−6.5 vs −5.5; LS mean difference −1.0; 95% CI, −2.0 to 0.0; P = .041), while quarterly dosing did not achieve statistical significance.²

Pooled analyses across both trials further strengthened the efficacy signal, with monthly ianalumab demonstrating a greater improvement in ESSDAI than placebo (LS mean difference −1.2; 95% CI, −2.0 to −0.4; P = .0031), alongside improvements in patient-reported outcomes.² Safety findings across both studies were comparable to placebo, with no new safety signals identified.²

RheumatologyLive spoke with Thomas Grader-Beck, MD, Associate Professor of Clinical Medicine at Johns Hopkins University of Medicine and a NEPTUNUS trial investigator, who noted that the Breakthrough Therapy designation reflects both the robustness of the phase 3 data and the magnitude of unmet need in Sjögren disease. He emphasized that the combined B-cell depletion and BAFF-R blockade may represent a clinically meaningful advance over prior therapeutic strategies if approved.

“We have to be a little bit careful with the statistical significance, since after the primary endpoint, the first key secondary was not met, so it's more of a nominal significance. But besides that, we have the ESSDAI, then we have the patient global activity, and the physician global activity, and then all the other secondary outcomes really have trended in the in the same direction. And so it's not, here is placebo better, here ianalumab is better. It's a consistent signature across 2 trials. That, for me, is very promising,” Grader-Beck said.

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