FDA Grants Breakthrough Therapy Designation to Ianalumab, First Potential Sjögren’s Targeted Therapy

The United States (US) Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Novartis’ ianalumab for the treatment of Sjögren disease. The company also announced their intent to submit regulatory applications for the therapy in early 2026, which would be the first targeted therapy for the disease if approved.¹

“This Breakthrough Therapy designation recognizes the potential for ianalumab to substantially improve the standard of care for people with Sjögren’s disease, who currently don't have effective treatment options for this debilitating disease,” Angelika Jahreis, Global Head, Development, Immunology, Novartis, said in a statement.¹ “We look forward to working with the agency through the regulatory review process with the hope of making ianalumab available to appropriate patients as quickly as possible.”

Ianalumab is a novel dual ADCC/BAFF-R targeting fully human monoclonal antibody designed to both deplete and inhibit B-cells, their activation, and survival. The therapy is being evaluated in the pivotal global, multicenter, phase 3 NEPTUNUS-1 and NEPTUNUS-2 studies, which have both met their primary endpoint of EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) change from baseline (CFB) at Week 48 compared to placebo.²

Key findings from both studies were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Thomas Grader-Beck, MD, Associate Professor of Clinical Medicine at Johns Hopkins University of Medicine.²

NEPTUNUS-1 compared monthly ianalumab 300 mg (n = 137) with placebo (n = 138), while NEPTUNUS-2 assessed ianalumab 300 mg given monthly (n = 168), every 3 months (n = 167), or placebo (n = 169). Both studies shared a primary endpoint of change from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 48, with key secondary endpoints including ESSDAI response (≥5-point reduction), achievement of low disease activity (ESSDAI <5), changes in ESSPRI, Sjögren’s Syndrome Symptom Diary, Physician and Patient Global Assessments, salivary flow rate, and safety through week 52.²

In NEPTUNUS-1, monthly ianalumab led to a greater mean reduction in ESSDAI at week 48 than placebo (−6.4 [SE, 0.47] vs −5.1 [SE, 0.46]), with a least-squares (LS) mean difference of −1.3 (SE, 0.66; 95% CI, −2.6 to 0.0; P = .0496). Similar findings were observed in NEPTUNUS-2, where monthly dosing achieved a greater ESSDAI reduction versus placebo (−6.5 [SE, 0.36] vs −5.5 [SE, 0.35]; LS mean difference −1.0 [SE, 0.51; 95% CI, −2.0 to 0.0; P = .041]), while quarterly dosing did not differ significantly from placebo (LS mean difference −0.5 [SE, 0.51; 95% CI, −1.5 to 0.5; P = .3413]). In pooled analyses, monthly ianalumab (n = 305) produced greater ESSDAI improvement than placebo (−6.5 [SE, 0.29] vs −5.3 [SE, 0.29]; LS mean difference −1.2 [SE, 0.41; 95% CI, −2.0 to −0.4; P = .0031]) and greater improvement in Patient Global Assessment scores (LS mean difference −4.9 [SE, 1.73; 95% CI, −8.3 to −1.5; P = .0049]). Improvements were also seen across multiple secondary endpoints, including salivary flow in patients with baseline stimulated flow >0.4 mL/min, with safety profiles comparable to placebo and numerically higher rates of serious adverse events and infections observed in placebo-treated patients.²

“Sjögren disease is a heterogeneous, systemic autoimmune disease with a substantial disease burden… Ianalumab 300 mg monthly improved both physician-assessed and patient-reported outcomes. There were consistent improvements in secondary outcome measures, more patients with ESSDAI low disease activity, improvements inPhGA, reductions in the overall disease burden as assessed by PaGA. sSF and SSSD oral dryness improved with ianalumab vs placebo in patients with sSF>0.4 mL/min at baseline, and there were numerical improvements in SSSD and ESSPRI,” Grader-Beck said during his presentation.²

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