SUMMARY

• Nipocalimab, a fully human, aglycosylated, effectorless immunoglobulin G1 (IgG1) anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody, is an investigational agent being studied for the treatment of adult and pediatric patients with generalized myasthenia gravis (gMG).^1-3
  • By interfering with the binding of IgG to FcRn, nipocalimab increases the lysosomal degradation of IgG, which reduces serum levels of total IgG and pathogenic IgG autoantibodies that cause myasthenia gravis (MG).
• A phase 2/3, open-label clinical trial (NCT05265273) is currently underway to evaluate the effect on total serum IgG, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of nipocalimab in children and adolescents with gMG who have an insufficient response to ongoing, standard of care (SOC) therapy.^3,4
  • Results through the active treatment phase (study day 1 through week 24) in adolescents (aged 12 to <18 years) are summarized below.^5,6

BACKGROUND

• MG is a rare, heterogeneous, neuromuscular, autoimmune disease characterized by fluctuating, fatigable muscle weakness. The symptoms may range from purely ocular to severe weakness of the limb, bulbar, or respiratory muscles. Majority of the patients develop ocular motor disturbances, including diplopia and/or ptosis, during the course of their disease. The disease course of MG is described as variable but progressive, with most patients having progressive weakness during the first 2 years that involves oropharyngeal and limb muscles. Up to 80% of patients with ocular onset develop gMG.^7,8
• MG is an antibody-mediated autoimmune disease of the neuromuscular juncture, with autoantibodies against acetylcholine receptors (AChRs) found in about 53-86% of pediatric patients with gMG. Antibodies against muscle-specific kinase occur in up to 40% of pediatric patients with MG who are seronegative for AChR antibodies. Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies may also be reported in pediatric patients with MG and can present as a milder, predominantly ocular phenotype.^7,9
  • Pediatric patients (onset before age 18) constitute approximately 10% of cases.⁷

CLINICAL DATA

Phase 2/3 Clinical Trial

An ongoing, open-label, uncontrolled multicenter clinical trial is currently evaluating the effect on total serum IgG, safety, tolerability, PK, and PD of nipocalimab in children and adolescents aged 2 to <18 years with gMG and insufficient clinical response to ongoing, stable SOC therapy.^3,4

Study Design/Methods

The study consists of a screening period of up to 4 weeks, a 24-week open-label active treatment phase where patients will receive nipocalimab intravenous (IV) Q2W, and an optional long-term extension phase. A safety follow-up assessment will be conducted 8 weeks after the last dose. For study design/methods, see Figure: Vibrance-mg Study Design.

Results

Strober et al (2024)^5,6 presented results through the active treatment phase (study day 1 through week 24) in adolescents (aged 12 to <18 years) with a clinical cutoff date of December 15, 2023.

Baseline Demographics

Baseline demographics of 7 adolescent patients (all with anti-AChR antibody positive gMG) are summarized in Table: Baseline Demographics and Disease Characteristics.

Efficacy

• The primary endpoint efficacy analysis was conducted in 5 adolescent patients who received ≥1 dose of nipocalimab and had ≥1 post-infusion sample evaluable for serum IgG levels at the time of the clinical cutoff.
• The mean percent change in total serum IgG from baseline to week 24 was -68.98% (standard error [SE], 7.561; 95% confidence interval [CI], -78.4 to -59.6).
• The median pre-dose (minimal) total serum IgG reduction from baseline to week 2 and week 24 was -72% and -69.87%, respectively.
• The mean change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score and Quantitative Myasthenia Gravis (QMG) score from baseline was -2.40 (SE, 0.187) and
  -3.80 (SE, 2.683) at week 24, respectively.
  • A total of 4 (80%) adolescent patients showed minimal symptom expression defined as MG-ADL 0/1 at week 24.

Safety

• Through week 24, there were no reports of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation or AEs of special interest observed in adolescent patients receiving nipocalimab (see Table: Summary of Adverse Events).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 October 2024.