Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation (FTD) to nipocalimab for the treatment of adult patients with moderate-to-severe Sjögren's disease (SjD). This designation follows the Breakthrough Therapy designation (BTD) that nipocalimab received in November 2024, making it the first and only investigational treatment to hold both designations for Sjögren's disease.
The FDA's Fast Track program is designed to accelerate the development and review of drugs that show promise in treating serious conditions and addressing unmet medical needs. For the millions of patients living with Sjögren's disease, this represents a significant step forward as currently no advanced therapies are approved to treat this debilitating autoimmune condition.
Addressing a Significant Unmet Need
Sjögren's disease is one of the most prevalent autoantibody-driven diseases, affecting approximately four million people worldwide. The condition disproportionately impacts women, who account for 90% of cases. Despite its prevalence, there are currently no FDA-approved treatments that address the underlying autoimmune mechanisms of the disease.
"This marks an additional important step forward in our efforts to bring meaningful advancements to people living with Sjögren's disease, a serious and debilitating condition," said Katie Abouzahr, M.D., Vice President, Autoantibody Portfolio and Maternal Fetal Disease Area Leader at Johnson & Johnson Innovative Medicine. "We look forward to continuing to work closely with the FDA to advance the clinical development of nipocalimab and potentially provide a much-needed treatment option for this community."
Sjögren's disease is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands. Patients typically experience mucosal dryness affecting the eyes, mouth, and vagina, along with joint pain and fatigue. More than half of patients have moderate to severe forms of the disease, with a disease burden comparable to rheumatoid arthritis or systemic lupus erythematosus.
The condition can lead to serious health consequences, including systemic complications and an increased risk of mortality. Notably, patients with Sjögren's disease have a 20 times greater risk of developing B-cell lymphomas compared to the general population.
Promising Clinical Results
The Fast Track designation follows positive results from the Phase 2 DAHLIAS study, which represented the first-ever positive results of an investigational FcRn blocker as a potential targeted therapy in Sjögren's disease. The study achieved its primary endpoint in the 15 mg/kg Q2W nipocalimab group, showing a greater than 70% relative average improvement in systemic disease activity at Week 24 compared to placebo and IgG reductions of more than 77%.
The DAHLIAS trial was a multicenter, randomized, placebo-controlled double-blind study involving 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 to receive intravenous nipocalimab at 5 or 15 mg/kg or placebo every 2 weeks through Week 22, with safety assessments conducted through Week 30.
The primary endpoint was change from baseline in the ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index) Score at Week 24. This index measures disease activity across 11 domains, including constitutional, lymphadenopathy, glandular, articular, cutaneous, respiratory, renal, muscular, peripheral nervous system, central nervous system, and hematological factors.
Trends of improvement were similarly observed across multiple secondary endpoints, and the safety and tolerability profile was consistent with other nipocalimab clinical studies.
Mechanism of Action and Development Program
Nipocalimab is an investigational monoclonal antibody designed to bind with high affinity to block FcRn (neonatal Fc receptor) and reduce levels of circulating immunoglobulin G (IgG) antibodies, potentially without impact on other immune functions. This mechanism targets autoantibodies and alloantibodies that underlie multiple conditions across three key segments: Rare Autoantibody diseases, Maternal Fetal diseases mediated by maternal alloantibodies, and Rheumatic diseases.
Johnson & Johnson is actively enrolling patients in the Phase 3 DAFFODIL study to further evaluate nipocalimab's efficacy and safety in Sjögren's disease. This marks the fourth Fast Track designation for nipocalimab, which has previously received this designation for hemolytic disease of the fetus and newborn (HDFN), warm autoimmune hemolytic anemia (wAIHA), generalized myasthenia gravis (gMG), and fetal neonatal alloimmune thrombocytopenia (FNAIT).
The FDA and European Medicines Agency (EMA) have granted several other key designations to nipocalimab, including Orphan drug status for multiple conditions and Priority Review for gMG in Q4 2024.
Future Implications
If approved, nipocalimab would represent a significant advancement in the treatment landscape for Sjögren's disease, potentially offering the first therapy that addresses the underlying autoimmune mechanisms of the condition. The dual designations of Fast Track and Breakthrough Therapy highlight the FDA's recognition of both the serious nature of Sjögren's disease and the promising potential of nipocalimab to address this unmet medical need.
For patients living with the chronic symptoms and systemic complications of Sjögren's disease, the accelerated development and review process could bring a much-needed treatment option closer to reality, potentially improving quality of life and functional capacity for millions worldwide.
