Topline Findings
- Novartis ianalumab Phase III success: Both NEPTUNUS-1 and NEPTUNUS-2 trials showed statistically significant improvements in Sjögren’s disease activity with a favorable safety profile.
- First targeted therapy potential: Ianalumab’s dual mechanism of B-cell depletion and BAFF-R inhibition positions it as a novel, disease-modifying treatment option for Sjögren’s disease.
- Growing treatment landscape: Recent advancements, including Johnson & Johnson’s Imaavy (nipocalimab) breakthrough, highlight increasing innovation and unmet need in Sjögren’s disease therapeutics.
Results from the Phase III NEPTUNUS-1 (NCT05350072) and NEPTUNUS-2 (NCT05349214) trials showed that Novartis’ ianalumab demonstrated statistically significant improvements in patients with Sjögren’s disease. According to the company, ianalumab, which employs a dual mechanism targeting B-cell depletion and BAFF receptor inhibition, has the potential to become the first targeted therapy for Sjögren’s disease.1
What Insights do the NEPTUNUS Trials Offer on Ianalumab’s Efficacy?
"Sjögren’s 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,” said Shreeram Aradhye, MD, president, development, chief medical officer, Novartis, in a press release.
NEPTUNUS-1 Trial Design and Endpoints
- The randomized, double-blind, two-arm, multicenter Phase III NEPTUNUS-1 trial evaluated the efficacy, safety, and tolerability of monthly ianalumab 300 mg subcutaneous (SC) compared to placebo in 276 patients for 52 weeks.
- The primary endpoint was the change from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score at week 48 compared to placebo.
- Key secondary endpoints included, but were not limited to, achieving ESSDAI response at weeks 24 and 48; change from baseline in stimulated whole salivary flow rate at week 48; change from baseline in Physician’s Global Assessment of disease activity at week 48; and change from baseline in Patient’s Global Assessment of disease activity at week 48.2
NEPTUNUS-2 Trial Design and Endpoints
- The randomized, double-blind, three-arm, multicenter NEPTUNUS-2 trial evaluated the clinical efficacy, safety, and tolerability of monthly ianalumab 300 mg or every three months in 506 patients compared to placebo for up to 52 weeks.
- The primary and secondary endpoints of the trial were identical to that of NEPTUNUS-1.3
Safety and Regulatory Plans
- The safety profile of ianalumab was reported to be favorable in both trials and generally well tolerated.
- Full results are expected to be presented at an upcoming medical meeting, with Novartis stating that it intends to submit the treatment to regulatory authorities globally.1
Broader Treatment Landscape and Disease Context
Recent clinical advances signal a turning point in the search for effective treatments for Sjögren’s disease. In March, Johnson & Johnson announced that the FDA had granted Breakthrough Therapy Designation to Imaavy (nipocalimab) as a treatment for Sjögren’s disease. Results from the Phase II DAHLIAS trial showed that Imaavy significantly improved disease activity and reduced immunoglobulin G levels by over 77% compared to placebo.4
According to Sjögren’s Advocate, Sjögren’s disease affects approximately three to four million people in the United States but is rarely diagnosed. While approximately 90% of those with the disease are women, men and children can also be affected.5
According to Novartis, Sjögren’s is considered one of the most prevalent rheumatic autoimmune diseases, affecting about 0.25% of the global population. Notably, an estimated 50% of cases remain undiagnosed.
Currently, no systemic treatments are approved and only limited symptomatic options exist that provide temporary and partial relief, underscoring the urgent need for effective targeted therapies.1 According to Medscape, the global prevalence of Sjögren’s disease is between 0.1% and 0.4%, with a median age of onset between 50 and 60 years.6
“Both Phase III trials demonstrate that ianalumab improves disease activity in patients with Sjogren’s disease,” continued Aradhye, in the press release. “These Phase III studies mark a significant milestone. We look forward to engaging with health authorities to discuss these findings in the near future.”
References
- Novartis announces both ianalumab Phase III clinical trials met primary endpoint in patients with Sjögren’s disease. 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
- Two-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome (NEPTUNUS-1). Clinicaltrials.gov. Accessed August 11, 2025. https://clinicaltrials.gov/study/NCT05350072?term=NEPTUNUS-1%20&rank=1
- Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome (NEPTUNUS-2). Clinicaltrials.gov. Accessed August 11, 2025. https://clinicaltrials.gov/study/NCT05349214?term=NEPTUNUS-2&rank=1
- Nipocalimab, the first and only investigational treatment to be granted U.S. FDA Breakthrough Therapy designation for the treatment of adults with moderate-to-severe Sjögren’s disease, has now received Fast Track designation. J&J. March 18, 2025. https://innovativemedicine.jnj.com/us/news-center/immunology/nipocalimab-the-first-and-only-investigational-treatment-to-be-granted-u-s-fda-breakthrough-therapy-designation-for-the-treatment-of-adults-with-moderate-to-severe-sjogrens-disease-has-now-received-fast-track-designation?utm_source=chatgpt.com
- SJOGREN'S IS COMMON. Sjorgen’s Advocate. Accessed August 11, 2025. https://www.sjogrensadvocate.com/sjogrens-is-common#:~:text=common%20is%20Sjogren's?-,How%20common%20is%20Sjogren's?,)%2C%20two%20closely%20related%20diseases.
- Sjogren Syndrome. Medscape. March 24, 2023. Accessed August 11, 2025. https://emedicine.medscape.com/article/332125-overview#a6
