Novartis' Ianalumab Becomes First Targeted Therapy to Show Efficacy in Sjögren's Disease Phase III Trials
Key Insights
Novartis announced that both NEPTUNUS-1 and NEPTUNUS-2 Phase III trials met their primary endpoints, demonstrating statistically significant improvements in disease activity for Sjögren's disease (search) patients.
Ianalumab represents the potential first and only targeted treatment for Sjögren's disease (search), a chronic autoimmune condition affecting approximately 0.25% of the population with limited current treatment options.
The dual-mechanism monoclonal antibody combines B-cell depletion and BAFF-R (search) inhibition, showing favorable safety profiles across the 52-week treatment period.
Novartis announced positive top-line results from two pivotal Phase III trials evaluating ianalumab (VAY736) in adults with active Sjögren's disease (search), marking a potential breakthrough for patients with this chronic autoimmune condition. Both NEPTUNUS-1 and NEPTUNUS-2 trials met their primary endpoints, demonstrating statistically significant improvements in disease activity compared to placebo.
The results represent the first ever global Phase III trials to demonstrate statistically significant reduction in disease activity for Sjögren's disease (search), positioning ianalumab as the potential first and only targeted treatment approved for this condition.
"Sjögren's disease (search) 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, M.D., President of Development and Chief Medical Officer at Novartis. "Both Phase III trials demonstrate that ianalumab improves disease activity in patients with Sjögren's disease."
Trial Design and Results
The NEPTUNUS pivotal trials achieved their primary endpoint of improving disease activity measured by a reduction in EULAR Sjögren's syndrome disease activity index (ESSDAI), a multi-dimensional disease activity measurement. NEPTUNUS-1 enrolled 275 patients in a randomized, double-blind, 2-arm multicenter trial evaluating ianalumab 300 mg subcutaneous monthly compared with placebo for 52 weeks. NEPTUNUS-2 included 504 patients in a 3-arm design comparing ianalumab 300 mg subcutaneous monthly or every 3 months versus placebo for up to 52 weeks.
Both trials were designed to provide comprehensive data on ianalumab's potential as a targeted treatment for Sjögren's disease (search) in patients with active extraglandular disease. Ianalumab demonstrated a favorable safety profile and was well tolerated across both studies.
Dual Mechanism of Action
Ianalumab is a novel fully human monoclonal antibody with a dual mechanism of action targeting B cells (search), which play a significant role in Sjögren's disease (search) by causing an autoimmune response that leads to inflammation and tissue damage. The drug combines B-cell depletion via antibody-dependent cellular toxicity (ADCC) and interruption of BAFF-R (search) mediated signals of B cell function and survival.
The therapeutic approach addresses the underlying pathophysiology of Sjögren's disease (search), where B cell dysfunction drives the autoimmune response. In previous clinical trials, ianalumab showed promising efficacy and favorable safety profiles in Sjögren's disease, systemic lupus erythematosus (search), and immune thrombocytopenia (search).
Addressing Significant Unmet Need
Sjögren's disease (search) is a systemic, chronic autoimmune disorder that causes inflammation and tissue damage throughout the body. It primarily affects exocrine glands, leading to excessive dryness, with over 90 percent of patients experiencing dry eyes and dry mouth. The disease affects approximately 0.25 percent of the population, with an estimated 50 percent remaining undiagnosed.
The condition disproportionately affects women, occurring nine times more frequently than in men. Beyond the characteristic dryness, patients experience fatigue and widespread pain, with 30-40 percent developing extraglandular organ involvement affecting skin, musculoskeletal system, kidneys, lungs and other organs. Patients with Sjögren's disease (search) also face an increased risk of lymphoma.
Currently, there are no systemic treatments approved for Sjögren's disease (search), with only limited symptomatic treatments available to provide temporary and partial relief. This significant treatment gap highlights the critical need for effective targeted therapies.
Regulatory Path Forward
Ianalumab has received Fast Track Designation from the US Food and Drug Administration, recognizing the urgent medical need for effective treatments in this patient population. Novartis plans to present the NEPTUNUS-1 and NEPTUNUS-2 data at an upcoming medical meeting and submit the drug to health authorities globally.
The company is also investigating ianalumab's potential across various B cell-driven autoimmune diseases, including immune thrombocytopenia (search), systemic lupus erythematosus (search), lupus nephritis (search), warm autoimmune hemolytic anemia, and diffuse cutaneous systemic sclerosis. Patients currently enrolled in the NEPTUNUS trials have been offered the opportunity to continue in long-term extension studies.
Ianalumab originates from an early collaboration with MorphoSys AG, which Novartis acquired in 2024, further strengthening the company's autoimmune disease portfolio.