• 16 Sep 2024
• Admin
• News Article

J & J Seeks EU Approval of Nipocalimab to Treat People Living with Generalised Myasthenia Gravis

Overview

Janssen-Cilag International NV, a Johnson & Johnson company, announced the submission of the Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking first approval of nipocalimab for the treatment of people living with generalised myasthenia gravis (gMG).

Phase 3 Vivacity-MG3 Study Data

• 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 Myasthenia Gravis - Activities of Daily Living (MG-ADL)a 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 percent of the gMG patient population, making Vivacity-MG3 the first registrational 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 generalised 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 EMA in their review of the data supporting the submission.”

Nipocalimab

Nipocalimab is the first 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).

MG-ADL Assessment

MG-ADL (Myasthenia Gravis – Activities of Daily Living) provides a rapid clinical assessment of the patient’s recall of symptoms impacting activities of daily living, with a total score range of 0 to 24; a higher score indicates greater symptom severity.

Antibodies in Active Patients

Positive patients include anti-acetylcholine receptor positive antibody (AChR+), anti-muscle specific tyrosine kinase positive antibody (MuSK+) and/or anti-low density lipoprotein receptor-related protein 4 positive antibody (LRP4+).

Overall Adverse Events

• The overall incidence of adverse events (AEs), serious adverse events (SAEs) and AEs leading to discontinuation were similar to that in the placebo plus SOC group. 
• Specifically, 81.6 per cent of patients (n=80) treated with nipocalimab plus SOC experienced AEs, closely matched by 82.7 percent (n=81) in the placebo plus SOC group. 
• Serious AEs were reported by 9.2 per cent of patients (n=9) in the nipocalimab plus SOC group compared to 14.3 per cent (n=14) in the placebo plus SOC group.

Patients who received nipocalimab plus current SOC had a mean change of -4.70 [standard error (SE) 0.329]. Patients on placebo plus current SOC had a mean change of -3.25 (SE 0.335); difference of least-squares (LS) means -1.45 [0.470]; P=0.002.

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, e.g., anti-acetylcholine receptor [AChR], anti-muscle-specific tyrosine kinase [MuSK] or anti-lipoprotein-related protein 4 [LRP4], that can block or disrupt normal functioning, preventing signals from transferring from nerves to muscles. 
• The disease impacts between 56,000 and 123,000 people in Europe and 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 percent of individuals diagnosed with MG are women, and about one in five of those women are of child-bearing potential.

Disease Symptoms

• Initial disease manifestations are usually ocular but in 85 per cent or more the disease generalises (gMG), which is characterised 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. 
• Although gMG may be managed with current SOC therapies, research is needed to develop new treatments 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 condition where unmet need remains high. 
• Antibody positive or negative adult gMG patients with insufficient response (MG-ADL =6) to ongoing standard of care (SOC) therapy were identified and 199 patients, 153 of which were antibody positive, enrolled in the 24-week double-blind placebo-controlled trial. 
• Randomisation 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-ADLb 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 Foetal 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 foetus.

Key Designations from FDA to Nipocalimab

The European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have granted several key designations to nipocalimab including:

• EU EMA Orphan medicinal product designation for HDFN in October 2019.
• US FDA Fast Track designation in haemolytic disease of the foetus and newborn (HDFN) and warm autoimmune haemolytic anaemia (wAIHA) in July 2019, gMG in December 2021 and foetal neonatal alloimmune thrombocytopenia (FNAIT) in March 2024.
• US FDA Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023.
• US FDA Breakthrough Therapy designation for HDFN in February 2024.