Johnson & Johnson announced positive results from the Phase 2 DAHLIAS study, revealing that nipocalimab, an investigational FcRn blocker, led to significant clinical improvements in patients with moderate-to-severe Sjögren's disease (SjD). The study demonstrated improvements in disease activity scores and a substantial reduction in IgG levels after 24 weeks of treatment.
The data, presented at the American College of Rheumatology (ACR) Convergence 2024, highlight nipocalimab's potential to address the underlying causes of SjD, a chronic autoimmune disease affecting approximately four million people worldwide. The FDA has granted Breakthrough Therapy Designation to nipocalimab for SjD based on these findings.
Key Findings from the DAHLIAS Study
The DAHLIAS study (NCT04969812) was a Phase 2 multicenter, randomized, placebo-controlled, double-blind trial involving 163 adults with moderately-to-severely active primary SjD. Participants were randomized to receive intravenous nipocalimab at 5 mg/kg, 15 mg/kg, or placebo every two weeks for 24 weeks.
The primary endpoint, change from baseline in the ClinESSDAI score at Week 24, was met with statistical significance. Patients receiving nipocalimab also showed significant reductions in IgG levels, including autoantibodies. Notably, improvements in ClinESSDAI were most pronounced in participants with high baseline levels of anti-Ro and anti-La autoantibodies.
Impact on Disease Activity and Symptoms
According to Ghaith Noaiseh, M.D., Associate Professor at The University of Kansas Medical Center, the reduction in IgG and pivotal autoantibodies, particularly anti-Ro antibodies, associated with improvements in systemic disease activity and saliva production, represents an exciting advance. He also noted the encouraging trend in patient-reported measures.
Patients reported a decrease in symptoms, with numerical improvements compared to placebo in key areas such as mouth dryness, eye dryness, vaginal dryness, fatigue, and joint pain. Objective salivary flow increased by at least 50% from baseline in 32.7% of patients in the high-dose nipocalimab group (15 mg/kg) compared to 16% in the placebo group at Week 24.
Mechanism of Action and Future Directions
Nipocalimab is a monoclonal antibody designed to block FcRn, reducing levels of circulating IgG antibodies without impacting other immune functions. This mechanism is believed to be crucial in addressing autoantibody-driven diseases like Sjögren's.
Federico Zazzetti, Director, Rheumatology, Global Medical Affairs Lead at Johnson & Johnson Innovative Medicine, emphasized the unmet need for new immunoselective treatments for SjD. He stated that Johnson & Johnson is committed to continued research to address this need, highlighting the potential of nipocalimab in a disease with limited treatment options.
About Sjögren's Disease
Sjögren's disease is a chronic autoimmune condition characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands. It affects approximately four million people worldwide, with women being nine times more likely to be affected than men. Common symptoms include mucosal dryness, joint pain, and fatigue. More than 50% of patients have moderate to severe forms of the disease, which can significantly impair quality of life and increase mortality risk.
