Johnson & Johnson's nipocalimab has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderate-to-severe Sjögren's disease (SjD). This designation aims to expedite the development and review of nipocalimab, an investigational monoclonal antibody, for this debilitating autoimmune condition affecting approximately four million people worldwide. The BTD is supported by positive Phase 2 DAHLIAS study results, marking it as the first FcRn blocker to demonstrate significant improvements in SjD.
The Breakthrough Therapy Designation is reserved for investigational medicines intended to treat serious conditions, where preliminary clinical evidence indicates a substantial improvement over available therapies. Sjögren's disease, characterized by autoantibody production and chronic inflammation, often leads to mucosal dryness, joint pain, and fatigue, significantly impacting patients' quality of life. Current treatments primarily address symptoms, leaving a significant unmet need for therapies targeting the underlying causes of the disease.
Phase 2 DAHLIAS Study
The Phase 2 DAHLIAS study (NCT04969812) was a multicenter, randomized, placebo-controlled, double-blind trial evaluating nipocalimab in adults with moderately to severely active primary Sjögren's disease. The study included 163 participants who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies. Participants were randomized to receive intravenous nipocalimab at 5 mg/kg or 15 mg/kg, or placebo every two weeks through Week 22, alongside standard of care. The primary endpoint was the change from baseline in the ClinESSDAI score at Week 24.
Results from the DAHLIAS study, presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress, demonstrated a greater than 70% relative improvement in systemic disease activity at Week 24 in participants receiving nipocalimab 15 mg/kg compared to placebo. Key secondary endpoints included multiple organ system assessments using the ESSDAI, physician global assessment of disease severity, and patient-reported outcomes such as the ESSPRI.
Nipocalimab Mechanism of Action
Nipocalimab is an investigational monoclonal antibody designed to selectively block the neonatal Fc receptor (FcRn), reducing levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies, without broadly impacting other immune functions. By blocking IgG binding to FcRn in the placenta, nipocalimab may also prevent the transplacental transfer of maternal alloantibodies to the fetus.
Ongoing and Future Development
Johnson & Johnson is currently conducting a Phase 3 study to further evaluate the efficacy and safety of nipocalimab in Sjögren's disease. Nipocalimab has received multiple designations from the FDA and EMA, including Fast Track designation, Orphan Drug status, and Breakthrough Therapy designation for various autoantibody-driven diseases, including hemolytic disease of the fetus and newborn (HDFN), warm autoimmune hemolytic anemia (wAIHA), generalized myasthenia gravis (gMG), and fetal neonatal alloimmune thrombocytopenia (FNAIT).
"Today's announcement marks an important step forward in the continued research and development of nipocalimab... 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, Vice President, Rheumatology, Immunology Disease Area Leader, Johnson & Johnson Innovative Medicine.
