• 31 Aug 2024
• Admin
• News Article

Johnson & Johnson Seeks US FDA Approval for Nipocalimab

Johnson & Johnson seeks US FDA approval for nipocalimab to treat people living with generalized myasthenia gravis

Overview

Johnson & Johnson announced the submission of a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) seeking the first approval of nipocalimab globally for the treatment of people living with generalized myasthenia gravis (gMG).

Phase 3 Vivacity-MG3 Study

• The application included data from the phase 3 Vivacity-MG3 study which showed that outcomes for a broad population of antibody positive participants who received nipocalimab plus standard of care (SOC) were superior compared to those who received placebo plus SOC. 
• The primary endpoint of the study measured improvement in the MG-ADLa score from baseline over 24 weeks and study participants included anti-AChR+, anti-MuSK+, and anti-LRP4+b antibody positive adults, which account for approximately 95 per cent of the gMG patient population, making Vivacity-MG3 the first-and-only study to demonstrate sustained disease control in these subtypes. Safety and tolerability were consistent with other nipocalimab studies.

From Johnson & Johnson Innovative Medicine

• "We are encouraged by the potential of nipocalimab to provide sustained disease control for people living with generalized myasthenia gravis, a chronic, life-long disease," said Bill Martin, Ph.D., global therapeutic area head, neuroscience, Johnson & Johnson Innovative Medicine. 
• "The filing for approval of nipocalimab represents an important step forward as Johnson & Johnson continues to push the boundaries of research to develop innovative solutions to treat autoantibody-driven diseases, building on decades of expertise in neuroscience and immunology. We look forward to working with the FDA in their review of the data supporting the submission."   

About Nipocalimab

Nipocalimab is the first-and-only FcRn blocker to demonstrate sustained disease control measured by improvement in MG-ADL when added to background SOC compared with placebo plus SOC over a period of six months of consistent dosing (every other week)c, which is the longest period of controlled safety and efficacy assessment of an FcRn blocker in gMG.

J & J Presentation of Data on Nipocalimab

• Earlier this year at the American Academy of Neurology Annual Meeting, Johnson & Johnson presented data focused on the molecular properties of nipocalimab. 
• Characteristics such as its high binding affinity and specificity to the immunoglobulin G (IgG) binding site of FcRn have the potential to differentiate nipocalimab in the FcRn blocker class of treatments.
• These properties, along with the dosing regimen chosen for the study, are thought to lower IgG, including IgG autoantibodies in diseases such as gMG and other autoantibody-driven diseases.

About Myasthenia Gravis

• Myasthenia gravis (MG) is an autoantibody disease in which autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signalling, and impair or prevent muscle contraction. 
• In MG, the immune system mistakenly attacks proteins at the neuromuscular junction by producing antibodies (e.g., anti-acetylcholine receptor [AChR], anti-muscle-specific tyrosine kinase [MuSK] or anti-low density lipoprotein-related protein 4 [LRP4]) that can block or disrupt normal functioning, preventing signals from transferring from nerves to muscles.
• The disease impacts an estimated 700,000 people worldwide. 
• The disease affects both men and women and occurs across all ages, racial and ethnic groups, but most frequently impacts young women and older men. 
• Roughly 50 per cent of individuals diagnosed with MG are women, and about one in five of those women are of child-bearing potential.

Disease Manifestations & Symptoms

• Initial disease manifestations are usually ocular but in 85 per cent or more cases, the disease generalizes (gMG), which is characterized by fluctuating weakness of the skeletal muscles leading to symptoms like limb weakness, drooping eyelids, double vision and difficulties with chewing, swallowing, speech, and breathing. 
• Approximately 100,000 individuals in the US are living with gMG. Although gMG may be managed with current conventional therapies, new therapies are needed for those who may not respond well enough to or tolerate these options.

Phase 3 Vivacity-MG3 Study

• The phase 3 Vivacity-MG3 study was specifically designed to measure sustained efficacy and safety with consistent dosing in this unpredictable chronic disease where unmet need remains high. 
• Antibody positive or negative adult gMG patients with insufficient response (MG-ADL =6) to ongoing SOC therapy were identified and 199 patients, 153 of which were antibody positive, enrolled in the 24-week double-blind placebo-controlled trial. 
• Randomization was 1:1, nipocalimab plus current SOC (30 mg/kg IV loading dose followed by 15 mg/kg every two weeks) or placebo plus current SOC. 
• Baseline demographics were balanced across arms (77 nipocalimab, 76 placebo). 
• The primary endpoint of the study was mean change in MG-ADLa score from baseline over Weeks 22, 23 and 24 in antibody positive patients. 
• A key secondary endpoint included change in Quantitative Myasthenia Gravis (QMG) score, which is a 13-item assessment by a clinician that quantifies MG disease severity. 
• Long-term safety and efficacy were further assessed in an ongoing OLE phase.

About Nipocalimab

• Nipocalimab is an investigational monoclonal antibody, purposefully designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, while preserving immune function without causing broad immunosuppression. 
• This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including Rare Autoantibody diseases, Maternal Fetal diseases mediated by maternal alloantibodies and Prevalent Rheumatology. 
• Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.