SUMMARY

• Nipocalimab is an investigational, fully human, high-affinity, aglycosylated, effectorless immunoglobulin G1 (IgG1), anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody that is being studied for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients.^1-3
• In a phase 2, randomized, double-blind, placebo-controlled trial in adult patients with gMG, 22 (40.7%) patients were positive for antidrug antibodies (ADAs) through day 113 and 8 (14.8%) patients were positive for neutralizing antibodies (NAbs) in the combined nipocalimab group.² 

CLINICAL DATA

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)² conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of nipocalimab in adult patients with gMG who had an insufficient response to ongoing, stable standard-of-care (SOC) therapy.

Study Design/Methods

• Patients (≥18 years of age) with anti-acetylcholine receptor (anti-AChR) or anti-muscle-specific tyrosine kinase (anti-MuSK) antibody-positive gMG (Myasthenia Gravis Foundation of America class II, III, or IVa) were included in the study.
• The study included a 4-week screening period, followed by an 8-week, double-blind treatment period. Post treatment follow-up assessment was performed for a period of 8 weeks.
• In addition to SOC therapy, eligible patients were randomized 1:1:1:1:1 to receive nipocalimab 5 mg/kg once every 4 weeks (Q4W), nipocalimab 30 mg/kg Q4W, nipocalimab 60 mg/kg single dose, nipocalimab 60 mg/kg every 2 weeks (Q2W), or placebo Q2W (5% dextrose in water).
• Exploratory endpoints included the incidence of ADAs and NAbs to nipocalimab.
  • ADAs and NAbs to nipocalimab were assessed using electrochemiluminescence immunoassay method and cell-based Fluorescence Activated Cell Sorting method, respectively.

Results

• A total of 68 patients (nipocalimab, n=54; placebo, n=14) were randomized to receive treatment.
• Post treatment serum samples from 54 patients treated with nipocalimab were evaluated for ADAs. The incidence of ADA through day 113 (16 weeks) in the nipocalimab- and placebo-treated groups was reported in 22 (40.7%) patients and 1 (7.1%) patient, respectively.
  • In 35.8% of samples from the combined nipocalimab-treated group tested positive for ADAs on day 15; however, the ADA-positive rates decreased at subsequent visits (from 12.2% on day 29 to 8.7% on day 113).
  • The ADA-positive rates at day 29 and beyond were similar between the nipocalimab- and placebo-treated groups, ranging from 7.7% on day 29 to 10.0% on day 113. The ADA titers were generally low (≤1:480).
• Overall, 8 (14.8%) patients in the nipocalimab group were positive for NAbs.
• Comparisons of median serum nipocalimab or medium serum IgG concentrations between ADA-positive and ADA-negative patients over time showed that the presence of ADA did not affect the PK or IgG lowering of nipocalimab and was not associated with reduced clinical efficacy (Myasthenia Gravis-Activities of Daily Living change from baseline over time) or adverse events.
• The incidence of NAb was too low to assess its effect on PK or PD.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 14 November 2024.