Exploring the Potential of Ianalumab in Primary Sjögren's Syndrome: Clinical Efficacy and Challenges Ahead

Neptunus-1 and Neptunus-2 reported that ianalumab produced a statistically significant reduction in systemic disease activity at 48 weeks; pooled monthly-dosing arms favored the investigational antibody over placebo on the prespecified primary endpoint.

The pooled, randomized late-stage analyses used change from baseline in the ESSDAI at Week 48 as the primary endpoint. Monthly ianalumab dosing showed an average ESSDAI decline of roughly 6.5 points versus about 5.3 points with placebo (between-group difference ≈1.2 points) and reached statistical significance in the combined analysis. Some dosing schedules and a three-arm study did not consistently separate from placebo, so the signal is promising but not uniformly robust across study-level comparisons.

Placebo arms demonstrated notable directional improvement across endpoints, complicating interpretation of absolute effect size and highlighting trial-design challenges in Sjögren’s. Contributing factors may include heterogeneous baseline activity, natural symptom fluctuation and regression to the mean among enrolled participants, selection or enrichment effects, and limited sensitivity of outcome instruments to detect biologically driven change. These considerations temper enthusiasm for pooled results and argue for prespecified, study-level confirmation.

Adverse event rates were comparable between ianalumab and placebo, with no new safety signals identified and similar frequencies of serious adverse events; one death was reported in the placebo arm of Neptunus-1. Tolerability appears acceptable within these study populations, while interpretation of safety data takes into account routine monitoring practices for B-cell–targeting therapies and vigilance for immune-related events.

Key Takeaways:

• Pooled analyses from Neptunus-1/2 show a statistically significant reduction in systemic disease activity at 48 weeks with monthly ianalumab dosing—representing a potential first-in-class systemic signal in primary Sjögren’s.
• Patients with active systemic Sjögren’s disease are the immediate population impacted, with implications for rheumatology clinics and specialty referral centers managing complex autoimmune care.
• Anticipated next steps include regulatory submission and review alongside confirmatory, prespecified study-level analyses and trial-design refinements to address placebo response and optimize dosing for clinical uptake and reimbursement discussions.