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 FcRn blocker, for a condition lacking approved advanced treatments.
Clinical Significance
Terence Rooney, vice president at Johnson & Johnson Innovative Medicine, emphasized the importance of this milestone, noting that nipocalimab is the first investigational FcRn blocker to demonstrate positive results in a Phase 2 study for Sjögren's disease. 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 data were presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress.
DAHLIAS Trial Details
The DAHLIAS study (NCT04969812) is a Phase 2, multicenter, randomized, placebo-controlled, double-blind trial. It enrolled 163 adults aged 18-75 with moderately-to-severely active primary SjD who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies. Participants were randomized 1:1:1 to receive intravenous nipocalimab at 5 or 15 mg/kg or placebo every two weeks through Week 22, alongside standard of care. Safety assessments continued through Week 30. The primary endpoint was the change from baseline in the ClinESSDAI score at Week 24.
Select secondary endpoints included:
- European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)
- Disease Activity Level (DAL) response
- Physician Global Assessment of Disease Severity (PhGA)
- Sjögren's Tool for Assessing Response (STAR)
- Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS)
- European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI)
- Sjögren's Symptoms tool
Nipocalimab Mechanism
Nipocalimab is a monoclonal antibody designed to bind with high affinity to FcRn, reducing levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies. This mechanism potentially avoids impacting other immune functions. Blockade of IgG binding to FcRn in the placenta may also prevent the transplacental transfer of maternal alloantibodies to the fetus.
Sjögren's Disease Context
Sjögren's disease is a chronic autoimmune condition affecting an estimated four million people worldwide, with a 9:1 female-to-male ratio. It is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands. Common symptoms include mucosal dryness, joint pain, and fatigue. More than 50% of patients have moderate-to-severe disease, with a disease burden comparable to rheumatoid arthritis or systemic lupus erythematosus. Patients with SjD also face a significantly elevated risk (up to 20 times higher) of developing B-cell lymphomas compared to the general population, and those with high activity in multiple organ systems have up to a five-fold increased mortality risk.
Prior Designations
Nipocalimab has received several designations from the FDA and EMA, including Fast Track designation for hemolytic disease of the foetus and newborn (HDFN) and warm autoimmune hemolytic anaemia (wAIHA), Orphan Drug status for wAIHA and HDFN, and Breakthrough Therapy designation for HDFN.
