Johnson & Johnson's nipocalimab, an investigational antibody-based therapy, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderate to severe Sjögren's disease. This designation aims to expedite the development and review of therapies showing substantial improvement over existing options for serious conditions.
The breakthrough therapy designation was supported by data from the Phase 2 DAHLIAS clinical trial (NCT04969812). The trial demonstrated that patients with Sjögren's disease who received nipocalimab at a dose of 15 mg/kg experienced a reduction of more than 70% in systemic disease activity after 24 weeks, as measured by the Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI).
Targeting the Root Cause of Sjögren's
Sjögren's disease is an autoimmune condition characterized by an inflammatory attack on moisture-producing glands, leading to dry eyes and mouth. The disease is driven by self-reactive immunoglobulin G (IgG) antibodies, including anti-Ro (SS-A) and anti-La (SS-B). Currently, there are no disease-modifying therapies available to directly address the underlying cause of Sjögren's.
Nipocalimab is designed to block the neonatal Fc receptor (FcRn), which normally prevents IgG antibodies from being degraded. By blocking FcRn, nipocalimab reduces the levels of circulating IgG antibodies, thereby reducing disease activity and symptom severity.
DAHLIAS Trial Details
The DAHLIAS study enrolled 163 adults aged 18 to 75 with moderate to severe active primary Sjögren's disease, all of whom tested positive for anti-Ro60 and/or anti-Ro52 antibodies. Participants were randomized to receive nipocalimab at doses of 5 or 15 mg/kg, or a placebo, administered intravenously every two weeks.
Results from the trial indicated a significant reduction in Sjögren's disease activity in patients treated with nipocalimab compared to those receiving placebo. This was reflected in a 2.65-point difference in the clinESSDAI score in the 15 mg/kg group. Improvements were observed as early as four weeks and continued to increase up to 24 weeks.
Secondary measures also showed improvements in disease severity and patient-reported outcomes in the 15 mg/kg group. Both doses of nipocalimab led to substantial reductions in IgG levels, with a maximum decrease of 77.5% in the 15 mg/kg group and 63.8% in the 5 mg/kg group. Notable decreases in autoantibody levels, including anti-Ro60, anti-Ro52, and anti-SSB antibodies, were also observed.
The treatment was generally well-tolerated, with serious adverse events reported in 7.5% of patients receiving the 5 mg/kg dose, 7.4% of those treated with the 15mg/kg dose, and 5.4% of participants on the placebo.
"With no treatments currently approved that may directly address the underlying cause(s) of the disease, innovation is critically needed to improve patient outcomes in Sjögren’s disease," said Terence Rooney, MD, Johnson & Johnson Innovative Medicine’s vice president of rheumatology and immunology disease area leader.
These results were presented at the American College of Rheumatology (ACR) Convergence 2024 in Washington, D.C. Nipocalimab is also being investigated for other autoimmune diseases, including generalized myasthenia gravis.
