Ianalumab Improves Sjögren Disease Activity in 2 Phase 3 Trials

The NEPTUNUS-1 and NEPTUNUS-2 trials have both met their primary endpoints and demonstrated that ianalumab statistically significantly improved disease activity in people with Sjögren disease with active extraglandular disease, marking the first phase 3 trials to demonstrate such improvements and supporting Novartis’ planned biologics license application (BLA) for the indication.1

"Sjögren disease is a serious, progressive, systemic autoimmune disease, often unrecognized or misdiagnosed with a significant detrimental impact to quality of life, with very limited treatment options and an established unmet need. Both Phase III trials demonstrate that ianalumab improves disease activity in patients with Sjogren’s disease,” Shreeram Aradhye, MD, President of Development and Chief Medical Officer at Novartis said in a statement.1 “These Phase 3 studies mark a significant milestone. We look forward to engaging with health authorities to discuss these findings in the near future.”

Ianalumab, also known as VAY736, is a novel fully human monoclonal antibody designed with a dual mechanism of action combining B cell depletion via antibody-dependent cellular toxicity (ADCC) and interruption of BAFF- R mediated signals of B cell function and survival to treat various B cell-driven autoimmune diseases. In addition to Sjogren disease, ianalumab is also being evaluated for systemic lupus erythematosus, and immune thrombocytopenia.

NEPTUNUS-1 is a randomized, double-blind, 2-arm multicenter phase III trial (N=275) evaluating ianalumab 300 mg subcutaneous monthly compared with placebo for 52 weeks and NEPTUNUS-2 is a randomized, double-blind, 3-arm multicenter phase III trial (N=504) which evaluated ianalumab 300 mg subcutaneous every 3 months months compared with placebo for up to 52 weeks. Both primarily evaluated a reduction in EULAR Sjögren’s syndrome disease activity index (ESSDAI), a multi-dimensional disease activity measurement compared to placebo. The trials also demonstrated ianalumab’s favorable safety profile in Sjögren disease. Further data from the trials will be presented at upcoming medical meetings.

HCPLive recently also got an in depth look at ianalumab’s evaluations, as well as other emerging therapies, in lupus nephritis at the 62nd European Renal Association (ERA 2025) Congress held in Vienna, Austria, in June 2025, during a conversation with leading subject matter expert Sayna Norouzi, MD, director of the Glomerular Disease Clinic, Polycystic Kidney Disease Clinic, and GlomCon Glomerular Disease Fellowship Program at Loma Linda University Medical Center.

Multiple studies presented at ERA 2025 examined the impact of multiple agents being examined in completed or ongoing clinical trial programs, including obinutuzumab and anifrolumab, which target B-cell depletion through anti-CD20 and interferon alpha-beta receptor antagonism, respectively, in addition to ianalumab. In all, ERA 2025 featured 24 presentations and 62 total abstracts focused on lupus nephritis, potential therapies, impact on quality of life, and more. Beyond these, several potential therapeutic options leveraging different mechanisms, including complement C3 inhibition, CAR-T, and more, are being investigated in phase 1 or 2 trials.2,3

The uptick in promising therapies for lupus nephritis represent a shifting point for the disease in the last 5 years after years of dormancy and may soon address unmet needs that persist in the space, such as the the goal of achieving complete renal response. Watch the conversation with Norouzi below.

REFERENCES

1. Novartis announces both ianalumab Phase III clinical trials met primary endpoint in patients with Sjögren’s disease. News release. Novartis. August 11, 2025. Accessed August 11, 2025. https://www.novartis.com/news/media-releases/novartis-announces-both-ianalumab-phase-iii-clinical-trials-met-primary-endpoint-patients-sjogrens-disease

2. Duarte-Garcia A. A New Era for the Treatment of Lupus. Rheumatology.org. Published May 22, 2023. Accessed August 11, 2025. http://rheumatology.org/patient-blog/a-new-era-for-the-treatment-of-lupus

3. DelveInsight Business Research, LLP . Lupus Nephritis Clinical Trial Pipeline Experiences Momentum: DelveInsight Estimates a Diverse Pipeline Comprising 30+ Companies Working in the Domain. Prnewswire.com. Published December 3, 2024. Accessed August 11, 2025. https://www.prnewswire.com/news-releases/lupus-nephritis-clinical-trial-pipeline-experiences-momentum-delveinsight-estimates-a-diverse-pipeline-comprising-30-companies-working-in-the-domain-302320381.html