FDA grants breakthrough therapy status to nipocalimab for Sjögren’s disease
Positive results seen in adults with moderate to severe Sjögren’s in trial
Johnson & Johnson’s antibody-based therapy candidate nipocalimab has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for treating adults with moderate to severe Sjögren’s disease.
This status is meant to accelerate the development and regulatory review of investigational therapies intended to treat serious or life-threatening conditions — and is awarded based on preliminary evidence suggesting substantial improvement over available therapies.
The designation was supported by results from the Phase 2 DAHLIAS clinical trial (NCT04969812), which showed that Sjögren’s patients treated with nipocalimab at a 15 mg/kg dose had a reduction of systemic, or body-wide, disease activity of more than 70% after 24 weeks, or about six months.
“[This] announcement marks an important step forward in the continued research and development of nipocalimab,” Terence Rooney, MD, Johnson & Johnson Innovative Medicine’s vice president of rheumatology and immunology disease area leader, said in a company press release.
Rooney said it was the first medication of its type “to demonstrate positive results in a Phase 2 study in adult patients with moderate to severe Sjögren’s disease.”
Nipocalimab shown to reduce disease activity in patients
Sjögren’s disease occurs when the immune system launches an inflammatory attack, primarily targeted at the glands that produce tears and saliva. Symptoms include eye and mouth dryness, although other organs may also be affected. The condition is classified as primary when it appears isolated, or secondary if it follows another autoimmune disease.
The attacks in Sjögren’s are driven by self-reactive antibodies — commonly anti-Ro, or SS-A, and anti-La, or SS-B — that belong to a class of antibodies called immunoglobulin G, or IgG. Normally, a protein called neonatal Fc receptor, or FcRn, binds to circulating IgG antibodies and helps prevent them from being degraded.
To date, there are no disease-modifying therapies available for Sjögren’s patients.
“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,” Rooney said.
Nipocalimab is an antibody-based therapy designed to block FcRn and reduce the amount of IgGs. By lowering the levels of disease-causing autoantibodies, the treatment is expected to ease Sjögren’s symptoms and disease severity.
The DAHLIAS study tested the treatment’s safety and efficacy in 163 adults, ages 18 to 75, with moderate to severe active primary Sjögren’s disease. All participants were positive for anti-Ro60 and/or anti-Ro52 antibodies. Patients were randomly assigned to receive nipocalimab at doses of 5 or 15 mg/kg, or a placebo, every two weeks, by intravenous, or into-the-vein, infusion.
Those treated with nipocalimab experienced a significant reduction of Sjögren’s disease activity relative to participants given the placebo, the data showed. This was demonstrated by a reduction in the Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index, called clinESSDAI for short. ClinESSDAI measures systemic disease activity, with lower values representing less disease activity.
The response was demonstrated after four weeks of treatment, and continued to increase up to 24 weeks. Overall, a reduction in systemic disease activity of more than 70% was seen in patients receiving the higher dose compared with those on the placebo — a difference of 2.65 points in the clinESSDAI.
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.
Similar improvements with the 15 mg/dose were also seen in secondary measures, including other assessments of disease severity and patient-reported outcome measures. Efficacy outcomes in the 5 mg/kg nipocalimab group were generally similar to the placebo group.
Both doses led to substantial reductions in patients’ IgG levels, by a maximum of 77.5% with the 15 mg/kg dose, and by 63.8% with the 5 mg/kg dose, compared with the study’s start. There were also notable decreases in the levels of autoantibodies, including anti-Ro60, anti-Ro52, and anti-SSB antibodies.
The treatment was generally well tolerated, with serious adverse reported in 7.5% of patients receiving the 5 mg/kg dose, 7.4% of those treated with the 15mg/kg dose, and 5.4% of participants on the placebo.
The results were presented at the American College of Rheumatology (ACR) Convergence 2024, being held in Washington, D.C.
Nipocalimab also is being developed for other diseases, including generalized myasthenia gravis.
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