Key Takeaways

  • Monthly ianalumab significantly reduced systemic disease activity at week 48 in two phase 3 trials involving 779 patients with Sjögren’s disease

  • Neither trial demonstrated significant improvements in key patient-reported symptom measures or ESSDAI response rates

  • The findings support further evaluation of B-cell–targeted treatment

Monthly treatment with ianalumab (Novartis) significantly reduced systemic disease activity compared with placebo in two phase 3 clinical trials involving patients with active Sjögren’s disease, although the treatment did not demonstrate significant improvements in patient-reported symptoms.1

The findings, published in the New England Journal of Medicine, suggest that B-cell–targeted therapy may offer a potential disease-modifying approach for Sjögren’s disease, a systemic autoimmune condition associated with ocular dryness and salivary gland dysfunction.

The NEPTUNUS-1 and NEPTUNUS-2 trials, led by Xavier Mariette, MD, PhD, of Université Paris-Saclay and Hôpital Bicêtre in France, evaluated ianalumab, an investigational monoclonal antibody that depletes B cells and blocks the B-cell activating factor receptor.

The randomized, double-blind, placebo-controlled studies enrolled 779 patients with active Sjögren’s disease. NEPTUNUS-1 included 275 patients assigned to monthly subcutaneous ianalumab 300 mg or placebo. NEPTUNUS-2 included 504 patients assigned to ianalumab administered monthly, every 3 months, or placebo.

At week 48, monthly ianalumab achieved statistically significant reductions in the European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index (ESSDAI), the primary endpoint in both trials.

Compared with placebo, the between-group difference in ESSDAI scores was −1.3 points in NEPTUNUS-1 (P=.0496) and −1.0 points in NEPTUNUS-2 (P=.04).

However, neither trial demonstrated a significant improvement in the proportion of patients achieving an ESSDAI response, defined as a reduction of at least 5 points. Significant improvements were also not observed in patient-reported symptom measures, including the Sjögren’s Syndrome Symptom Diary and EULAR Sjögren’s Syndrome Patient Reported Index.

Serious adverse events occurred at similar rates across treatment and placebo groups. Nonserious injection-site and systemic injection-related reactions were more common among patients receiving ianalumab.

The trials were funded by Novartis.

Reference

1. Mariette X, 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