‘Proof of concept’ established for FcRn receptor blocker nipocalimab in Sjogren’s disease
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Patients with Sjögren’s disease treated with nipocalimab, a novel neonatal Fc receptor blocker, demonstrate significant improvement vs. those who receive placebo at week 24, according to data presented at the EULAR 2024 Congress.
“Approximately 4 million individuals worldwide have Sjögren’s disease,” Terence Rooney, MD, vice president of rheumatology and immunology disease area leader at Johnson & Johnson Innovative Medicine, told Healio. “It is nine times more common in women than men. There are currently no treatments that directly address the underlying causes of Sjögren’s disease.
“A clear need exists for patients living with Sjögren’s disease to have advanced therapies that target the underlying cause and systemic nature of the disease,” he added.
In the current phase 2 study, Jacques-Eric Gottenberg, MD, PhD, of Strasbourg University Hospital, in France, and colleagues assessed the efficacy and safety of nipocalimab (Johnson & Johnson) in a cohort of 163 patients with Sjögren’s disease.
“Nipocalimab is an investigational neonatal Fc receptor (FcRn) blocker and is specifically engineered as a targeted therapy that blocks the activity of FcRn, thus lowering the levels of immunoglobulin G, including pathogenic IgG autoantibodies — one of the key drivers of autoantibody-driven diseases such as Sjögren’s disease,” Rooney said.
The final analysis included 53 patients treated with nipocalimab 5 mg/kg, 54 patients treated with nipocalimab 15 mg/kg, and 56 patients in the placebo group. Change from baseline in the Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (clinESSDAI) score at week 24 served as the primary endpoint. The researchers also evaluated safety outcomes at week 30.
According to the researchers, the nipocalimab 15 mg/kg group bested placebo in terms of the primary endpoint (least squares mean difference for 15 mg/kg = –2.65; P = .002). The 5 mg/kg was also superior to placebo in clinESSDAI (lease squares mean difference = –0.34; P = .681).
“These late breaking results show nipocalimab is the first FcRn blocker to significantly improve Sjögren’s disease activity,” Rooney said. “Specifically, patients who received nipocalimab 15 mg/kg demonstrated a more than 70% greater relative average improvement on the primary endpoint, compared with patients who received placebo. Response was demonstrated as early as week 4 and continued to increase throughout the 24-week treatment period compared with patients receiving placebo.”
The 15 mg/kg dose also improved over placebo in a number of secondary outcome measures evaluated at week 24, including change from baseline in Global Assessment of Disease Severity (PhGA), change from baseline in ESSDAI score, treatment response via the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjogren’s Syndrome (CRESS), and disease activity level (DAL) response.
In addition, immunoglobulin G (IgG) and autoantibodies significantly decreased in a dose-dependent manner among patients treated with nipocalimab.
“Improvement trends were also observed in important patient-reported symptoms including mouth dryness, eye dryness and vaginal dryness,” Rooney said.
Patient-reported outcomes were also numerically improved among those in the nipocalimab 15 mg/kg group compared with those in the placebo group.
That said, the overall efficacy of nipocalimab 5 mg/kg was similar to that of placebo.
Serious adverse event rates were 7.5% for the nipocalimab 15 mg/kg group, 7.4% for 5 mg/kg and 5.4% for placebo. Severe infections or infections requiring IV anti-infective medications were reported in 3.8% of patients in the nipocalimab 15 mg/kg group, 1.9% for 5 mg/kg and 1.8% for placebo. According to the researchers, this outcome lacked a clear correlation with IgG nadir and none of these events were deemed related to study treatment. There were no opportunistic infections, severe hypoalbuminemia or fatalities reported.
“These findings establish proof of concept for nipocalimab in this disorder and support further evaluation in patients with moderate-to-severe autoantibody-positive Sjögren’s disease,” Rooney said. “The data presented at EULAR demonstrate the potential of nipocalimab in a disease where patients have very few treatment options.”
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Gottenberg JE. LBA0010. Presented at: EULAR 2024 Congress; June 12 to June 15, 2024, Vienna, Austria.
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