Novartis reports Week 108 NEPTUNUS results showing further reductions in Sjögren’s disease activity with monthly ianalumab, extending Phase III findings.
Written By: Pavani Polipaka, PharmD
Reviewed By: Pharmacally Editorial Team
Novartis presented two-year follow-up findings from its Phase III NEPTUNUS extension programme on November 10, 2026, at the American College of Rheumatology (ACR) Convergence 2026. Monthly treatment with investigational ianalumab (300 mg) was associated with further reductions in systemic disease activity through Week 108, with nearly two-thirds of continuously treated patients achieving low disease activity. The findings extend the results of the NEPTUNUS-1 and NEPTUNUS-2 trials, which met their primary endpoints at Week 48.
Ianalumab: A Dual-Action BAFF-R-Targeting Antibody
Ianalumab (VAY736) is an investigational, afucosylated monoclonal antibody targeting the B-cell activating factor receptor (BAFF-R). Its dual mechanism combines antibody-dependent cellular cytotoxicity (ADCC)-mediated B-cell depletion with inhibition of BAFF-mediated survival signalling.
Through Fc-region glycoengineering, ianalumab enhances binding to FcγRIIIa on natural killer cells, promoting the depletion of BAFF-R-expressing B cells. Simultaneously, BAFF-R blockade interrupts survival and activation signals. This approach is designed to address B-cell hyperactivity, a central feature of Sjögren’s disease, through two complementary mechanisms.
NEPTUNUS Phase III Programme: Trial Design and Endpoints
The Phase III programme comprised two randomized, double-blind, placebo-controlled trials evaluating subcutaneous ianalumab in adults with active Sjögren’s disease. NEPTUNUS-1 (NCT05350072) enrolled 275 participants randomized to monthly ianalumab 300 mg or placebo. NEPTUNUS-2 (NCT05349214) enrolled 504 participants and compared monthly and every-three-month administration of ianalumab 300 mg against placebo.
Both trials evaluated changes from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at Week 48 as their primary endpoint. The programme also assessed disease activity responses and patient-reported symptoms to evaluate the broader clinical effects of treatment.
Both Phase III Trials Meet Primary ESSDAI Endpoints
Monthly ianalumab met the primary endpoint in both studies. At Week 48, the least-squares mean difference in ESSDAI change compared with placebo was −1.3 points in NEPTUNUS-1 (95% CI, −2.6 to 0.0; p=0.0496) and −1.0 point in NEPTUNUS-2 (95% CI, −2.0 to 0.0; p=0.04).
By contrast, the every-three-month dosing regimen did not achieve statistical significance in NEPTUNUS-2, supporting monthly administration as the effective regimen evaluated in the programme.
However, the primary endpoint findings did not extend to key secondary outcomes. Neither trial demonstrated statistically significant between-group improvements in key symptom-related measures, including the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI) and Sjögren’s Syndrome Symptom Diary (SSSD), at Week 48. This indicates that improvements in systemic disease activity had not yet translated into statistically established benefits across the measured patient-reported outcomes after one year.
Two-Year Extension Shows Further Improvement in Disease Activity
The ongoing NEPTUNUS extension study (NCT05985915) provides additional evidence on longer-term treatment response. Of 666 eligible participants, 610 (91.6%) entered the extension, and 551 (90.3% of extension participants) completed assessments through Week 108. The analysis included patients receiving continuous monthly ianalumab and those originally assigned to placebo who switched to monthly treatment at Week 60.
Among patients receiving continuous ianalumab, mean ESSDAI reduction from the original core-study baseline increased from 6.5 points at Week 48 to 7.5 points at Week 108. In the placebo-switch group, the reduction increased from 5.1 to 6.5 points over the same period.
The proportion achieving low disease activity, defined as ESSDAI below 5, increased from 57.1% to 65.1% in the continuous-treatment group and from 50.4% to 60.9% following placebo crossover. Improvements in ESSPRI and SSSD were sustained with continuous treatment and observed after crossover. Among patients with baseline stimulated whole salivary flow above 0.4 mL/min, improvements were maintained through Week 96. In patients with lower baseline flow, no further decline was reported following crossover.
Safety Profile and Long-Term Follow-Up
In the controlled Phase III trials, serious adverse-event incidence was similar between ianalumab and placebo groups, although injection-site and systemic injection-related reactions occurred more frequently with ianalumab.
Longer-term safety findings through Week 204 showed comparable adverse-event and serious adverse-event rates between the continuous-treatment and placebo-switch groups, with no new safety findings reported. Continued monitoring will be important to characterize the long-term effects of B-cell depletion and BAFF-R blockade, particularly regarding immunoglobulin levels and infection risk.
Clinical Interpretation
The NEPTUNUS programme establishes that monthly ianalumab can reduce systemic disease activity in Sjögren’s disease, with further improvements observed during extended treatment. However, the placebo-adjusted ESSDAI differences at Week 48 remained modest, and significant benefits were not demonstrated across key symptom-related secondary endpoints.
The Week 108 findings are encouraging but represent descriptive changes from the original baseline rather than placebo-adjusted treatment effects. The absence of a concurrent placebo comparator after crossover and the open-label extension design also limit conclusions about the magnitude of sustained treatment benefit.
For Novartis, the findings strengthen the clinical evidence supporting BAFF-R-directed B-cell depletion in Sjögren’s disease. Whether longer treatment can translate into durable symptomatic improvements and meaningful preservation of glandular function will require further evaluation. Ianalumab therefore remains an investigational therapy pending regulatory review and additional long-term evidence.
Reference
Novartis ianalumab two-year data at ACR show further improvements in Sjögren’s disease activity, Novartis, 10 November 2026
Study of Efficacy and Safety of Ianalumab in Patients with Active Sjögren’s Syndrome (NEPTUNUS-1): NCT05350072.
Study of Efficacy and Safety of Two Dosing Regimens of Ianalumab in Patients with Active Sjögren’s Syndrome (NEPTUNUS-2): NCT05349214
ClinicalTrials.gov. Long-Term Extension Study of Ianalumab in Participants with Sjögren’s Syndrome (NEPTUNUS Extension): NCT05985915
About the Writer
Pavani Polepaka, Pharm.D., (Linkedin) is a clinically trained pharmacy professional with hands-on exposure to hospital settings and experience in patient case documentation, medical record review, adverse drug reaction (ADR) reporting, pharmacovigilance, literature review and patient counselling. She possesses a strong foundation in pharmacotherapy, drug safety, clinical research and evidence-based healthcare practices, with an interest in translating clinical evidence into scientifically accurate medical content. She demonstrates research and analytical skills through academic activities and medical literature evaluation.