The FDA has granted Breakthrough Therapy Designation to nipocalimab (Johnson & Johnson) for the treatment of moderate-to-severe Sjögren's disease (SjD), a chronic autoimmune condition characterized by dry eyes and dry mouth. This marks nipocalimab as the first and only therapy to receive this designation for Sjögren's disease, highlighting its potential to address the underlying causes of the disease.
The decision is based on data from the Phase 2 DAHLIAS study (NCT04968912), a randomized, double-blind, placebo-controlled trial involving 163 patients with moderate-to-severe Sjögren's disease. Participants received either nipocalimab at 5 mg/kg or 15 mg/kg, or a placebo, every two weeks for 24 weeks.
Significant Clinical Improvements
The DAHLIAS study demonstrated that nipocalimab led to statistically significant and clinically meaningful improvements in the Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI) score compared to placebo at week 24 (p<0.05). Improvements were observed as early as week 4 and continued throughout the treatment period. Secondary outcomes also showed improvements in multiple organ assessments, physician assessments, and composite tools for clinical trial endpoints, as well as improvements in patient-reported symptoms such as mouth, eye, and vaginal dryness.
According to Terence Rooney, MD, vice president and rheumatology and immunology disease area leader at Johnson & Johnson Innovative Medicine, "This 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."
Safety and Tolerability
The safety profile of nipocalimab in the DAHLIAS study was consistent with previous clinical trials. Serious adverse events were reported in 7.5% of patients in the 5 mg/kg group, 7.4% in the 15 mg/kg group, and 5.4% in the placebo group. Severe infections or infections requiring intravenous anti-infectives occurred in 3.8%, 1.9%, and 1.8% of individuals, respectively.
Addressing an Unmet Need
Sjögren's disease is more prevalent in women, with most diagnoses occurring after the age of 40. While dry eyes and dry mouth are hallmark symptoms, patients may also experience joint pain, swelling, stiffness, swollen salivary glands, skin rashes, vaginal dryness, persistent dry cough, and prolonged fatigue. The disease can also affect other organs, including the joints, thyroid, kidneys, liver, lungs, skin, and nerves.
Currently, there are no approved therapies that directly target the underlying cause of Sjögren's disease, leaving a significant unmet need for effective treatments. Nipocalimab's Breakthrough Therapy Designation underscores its potential to fill this gap.
Ongoing Phase 3 Development
Johnson & Johnson is currently conducting a Phase 3 study to further evaluate the efficacy and safety of nipocalimab in patients with moderate-to-severe Sjögren's disease. This ongoing research aims to confirm the promising results observed in the Phase 2 DAHLIAS trial and potentially bring a new treatment option to patients suffering from this debilitating condition.
