NEPTUNUS-1 and 2: Monthly Ianalumab Significantly Improves Sjögren Disease Activity

Subcutaneous ianalumab demonstrated significant improvements in Sjögren disease (SjD) activity, meeting the primary endpoints of the 2 phase 3 NEPTUNUS-1 and NEPTUNUS-2 studies evaluating the therapy.1

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.

“SjD is a heterogeneous, systemic autoimmune disease with a substantial disease burden. B cell hyperactivity and dysregulated BAFF/BAFF-R signaling are a hallmark of SjD pathogenesis,” Grader-Beck said during his presentation.1 “Ianalumab is an afucosylated, fully human, IgG1 mAb targeting B cells through a novel dual mechanism of action, by binding to BAFF-R, which causes depletion of B cells through enhanced ADCC and inhibition of B cell activation and survival via BAFF-R blockade.”

NEPTUNUS-1 evaluated ianalumab 300 mg monthly (n = 137) compared to placebo (n = 138) while NEPTUNUS-2 evaluated ianalumab 300 mg monthly (n = 168), ianalumab 300 mg every 3 months (n = 167), and placebo monthly (n = 169). Both studies shared a primary endpoint of EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) change from baseline (CFB) at Week 48 with ianalumab compared to placebo. Key secondary endpoints included ESSDAI response (≥5-point reduction) and achievement of low systemic disease activity (ESSDAI <5) at week 48, along with CFB and responses in EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) and Sjögren's Syndrome Symptom Diary (SSSD) scores, Physician Global Assessment (PhGA), Patient Global Assessment (PaGA), and Salivary Flow rate (sSF) at week 48, and safety and tolerability assessments through week 52. Participants who completed either study were eligible to continue in an extension study.1

Investigators found that in NEPTUNUS-1, patients receiving monthly demonstrated a greater mean reduction in ESSDAI score at week 48 compared with placebo (−6.4 [SE, 0.47] vs −5.1 [SE, 0.46]), corresponding to an LS mean difference of −1.3 (SE, 0.66; 95% CI, −2.6 to 0.0; P = .0496). In NEPTUNUS-2, monthly ianalumab similarly achieved a greater mean reduction in ESSDAI score versus placebo at week 48 (−6.5 [SE, 0.36] vs −5.5 [SE, 0.35]), with an LS mean difference of −1.0 (SE, 0.51; 95% CI, −2.0 to 0.0; P = .041). Ianalumab once every 3 months did not yield a significantly greater mean reduction in ESSDAI score versus placebo at week 48 (−6.0 [SE, 0.36]), with an LS mean difference of −0.5 (SE, 0.51; 95% CI, −1.5 to 0.5; P = 0.3413).1

“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.1

In pooled data, patients receiving ianalumab every month (n = 305) showed a greater reduction in ESSDAI score compared with placebo (−6.5 [SE, 0.29] vs −5.3 [SE, 0.29]), corresponding to an LS mean difference of −1.2 (SE, 0.41; 95% CI, −2.0 to −0.4; P = .0031). They also showed a greater improvement in PaGA score compared with placebo (−13.5 [SE, 1.23] vs −8.7 [SE, 1.21]), with an LS mean difference of −4.9 (SE, 1.73; 95% CI, −8.3 to −1.5; P = .0049).1

Ianalumab also demonstrated consistent improvements in both continuous and binary secondary end points. Patients with baseline stimulated sSF >0.4 mL/min also showed greater improvements in sSF with ianalumab 300 mg monthly vs placebo. In terms of safety, the overall incidence of adverse events (AEs) and serious AEs were comparable to that with placebo in both studies, with numerically higher rates of serious AEs and infections in placebo groups.

“In conclusion, ianalumab provided a clinically meaningful benefit to patients, as evidenced by significant improvements in disease activity and reductions in patient burden,” Grader-Beck said.1

Novartis is also evaluating ianalumab for other indications including primary immune thrombocytopenia.2

Grader-Beck’s disclosures include Novartis.

REFERENCES

1. Grader-Beck T, Mariette X, Finzel S, et al. Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren’s disease: Efficacy and safety results from two global Phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2). Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #LB24

2. Livingston R. Ianalumab Meets Primary Endpoint in Phase 3 Trial for Primary Immune Thrombocytopenia. HCPLive. Article. August 12, 2025. https://www.hcplive.com/view/ianalumab-meets-primary-endpoint-in-phase-3-trial-for-primary-immune-thrombocytopenia