SUMMARY

• Please refer to the local labeling for relevant information regarding immunogenicity with IMAAVY.
• In a phase 2, randomized, double-blind, placebo (PBO)-controlled trial in adult patients with generalized myasthenia gravis (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 IMAAVY group.¹ 

PRESCRIBING INFORMATION

Immunogenicity

• The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of nipocalimab-aahu or of other nipocalimab products.² 
• In clinical trials, antibodies to nipocalimab-aahu were detected in 49/102 (48%) adult and pediatric patients 12 years of age and older during 24-week treatment period.
• Out of the 49 patients who were positive for antibodies to nipocalimab-aahu, 19 (38.8%) patients had neutralizing antibodies to nipocalimab-aahu. There was no identified clinically relevant effect of antibodies, including neutralizing antibodies, to nipocalimab-aahu on the pharmacokinetics, pharmacodynamics, safety, or effectiveness of IMAAVY.

CLINICAL DATA

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)¹ conducted a phase 2, multicenter, randomized, double-blind, PBO-controlled clinical trial to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of IMAAVY 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 IMAAVY 5 mg/kg once every 4 weeks (Q4W), IMAAVY 30 mg/kg Q4W, IMAAVY 60 mg/kg single dose, IMAAVY 60 mg/kg every 2 weeks (Q2W), or PBO (5% dextrose in water) Q2W.
• Exploratory endpoints included the incidence of ADAs and NAbs to IMAAVY.
  • ADAs and NAbs to IMAAVY were assessed using electrochemiluminescence immunoassay method and cell-based Fluorescence Activated Cell Sorting method, respectively.

Results

• A total of 68 patients (IMAAVY, n=54; PBO, n=14) were randomized to receive treatment.
• Post treatment serum samples from 54 patients treated with IMAAVY were evaluated for ADAs. The incidence of ADA through day 113 (16 weeks) in the IMAAVY- and PBO-treated groups was reported in 22 (40.7%) patients and 1 (7.1%) patient, respectively.
  • In 35.8% of samples from the combined IMAAVY-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 IMAAVY- and PBO-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 IMAAVY group were positive for NAbs.
• Comparisons of median serum IMAAVY 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 IMAAVY and was not associated with reduced clinical efficacy as measured by Myasthenia Gravis Activities of Daily Living (MG-ADL) 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.