Nipocalimab Receives FDA Breakthrough Therapy Designation for Sjögren’s Disease
Key Insights
The FDA granted Breakthrough Therapy Designation to nipocalimab for treating moderate-to-severe Sjögren’s disease (search) in adults, addressing a critical unmet need.
This designation is supported by Phase 2 DAHLIAS study results, which demonstrated positive outcomes with nipocalimab in Sjögren’s disease (search) patients.
Nipocalimab is the first investigational FcRn (search) blocker to show positive results in a Phase 2 study for Sjögren’s disease (search), marking a significant advancement.
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 (search) (SjD). This marks a significant milestone as nipocalimab is the only investigational therapy to receive this designation for SjD, a chronic autoantibody disease affecting approximately four million people worldwide.
The BTD is supported by data from the Phase 2 DAHLIAS study, which evaluated the efficacy and safety of nipocalimab in adults with moderate-to-severe SjD. The study's findings, presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress, demonstrated the first positive results of an investigational FcRn (search) blocker as a potential targeted therapy for SjD.
Clinical Significance of Breakthrough Therapy Designation
The FDA grants BTD to expedite the development and review of investigational medicines intended to treat serious conditions, where preliminary clinical evidence indicates substantial improvement over existing therapies. Sjögren’s disease (search), characterized by autoantibody production and chronic inflammation, often leads to mucosal dryness, joint pain, and fatigue, significantly impacting patients' quality of life. Patients also face a higher risk of developing B-cell lymphomas (search), with mortality risk increasing up to five-fold in those with high disease activity across multiple organ systems.
Terence Rooney, Vice President, Rheumatology, Immunology Disease Area Leader at Johnson & Johnson Innovative Medicine, stated, "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 (search)."
Details of the DAHLIAS Phase 2 Study
The DAHLIAS study (NCT04969812 (search)) was a Phase 2 multicenter, randomized, placebo-controlled, double-blind trial. It assessed the effects of nipocalimab in participants with primary Sjögren’s disease (search). The study randomized 163 adults aged 18-75, who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies, to receive intravenous nipocalimab at 5 or 15 mg/kg, or placebo every two weeks through Week 22, alongside standard of care. Safety assessments were conducted through Week 30. The primary endpoint was the change from baseline in the ClinESSDAI Score at Week 24.
Secondary endpoints included multiple organ system assessments using the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI), physician assessment via the Physician Global Assessment of Disease Severity (PhGA), composite tools such as the Sjögren’s Tool for Assessing Response (STAR) and Composite of Relevant Endpoints for Sjogren’s Syndrome (CRESS), and patient-reported outcomes including the European League Against Rheumatism Sjögren’s Syndrome Patient-Reported Index (ESSPRI).
About Nipocalimab
Nipocalimab is an investigational monoclonal antibody designed to bind with high affinity to block FcRn (search), reducing levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies. This mechanism potentially avoids impacting other immune functions. The FDA has granted Fast Track designation to nipocalimab for hemolytic disease of the fetus and newborn (search) (HDFN), warm autoimmune hemolytic anemia (search) (wAIHA), generalized myasthenia gravis (search) (gMG), and fetal neonatal alloimmune thrombocytopenia (search) (FNAIT). Orphan drug status has also been granted for wAIHA, HDFN, gMG, chronic inflammatory demyelinating polyneuropathy (search), and FNAIT.
A Phase 3 study is currently underway to further evaluate nipocalimab in Sjögren’s disease (search).