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 3, randomized, double-blind, placebo-controlled trial in adults with gMG, nipocalimab was shown to increase mean low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels by 8.3% and 7.0% at week 24, respectively. The cholesterol to HDL ratio was <4 at week 24.¹
• In a phase 2, randomized, double-blind, placebo-controlled trial in adults with gMG, mild dose-dependent elevations of cholesterol, LDL and HDL were seen with nipocalimab as summarized below.³

CLINICAL DATA

VIVACITY-MG3

Vu et al (2024)¹ evaluated the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of nipocalimab in adults with gMG in a phase 3, randomized, multicenter, double-blind, placebo-controlled study.

Study Design/Methods

• Patients (≥18 years of age) with anti- acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK) or low-density lipoprotein receptor 4 (LRP4) antibody positive or seronegative (in all countries except France) gMG (MGFA Class IIa–IVb) were included in the study.
  • The safety analysis population included all randomized patients who received ≥1 dose (partial or complete) of any study treatment in the double-blind phase.
• The study consisted of a ≤4-week screening phase, followed by a 24-week, double-blind, placebo-controlled treatment phase, a variable-duration, open-label extension phase, and a safety follow-up at 8 weeks after the last infusion.
  • Patients who withdrew or discontinued after receiving any amount of the study intervention were required to complete a safety follow-up assessment at 8 weeks after the last dose.
• Eligible patients were randomized (1:1) to receive a loading dose of intravenous nipocalimab 30 mg/kg at week 0 followed by 15 mg/kg every 2 weeks or matching placebo through week 24 in addition to standard of care (SOC) therapy.

Results

• A total of 196 patients (nipocalimab, n=98; placebo, n=98) were included in the full analysis set.
• At week 24, mean LDL and mean HDL increased by 8.3% and 7.0%, respectively, and the cholesterol to HDL ratio was <4 (see Figure: Mean Percent (SE) Change in Lipids Over 24 Weeks).

• • Through week 24, there were no reports of major cardiovascular adverse events in the nipocalimab group and 3 reports in the placebo group.⁴ 

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)^3,5 conducted a phase 2, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy, PK, and PD of nipocalimab in adult patients with gMG who had an insufficient response to ongoing, stable SOC therapy.

Study Design/Methods

• Patients (≥18 years of age) with anti-AChR or anti-MuSK antibody positive gMG (MGFA 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 intravenous infusions of: nipocalimab 5 mg/kg once every 4 weeks (Q4W), 30 mg/kg Q4W, 60 mg/kg single dose, or 60 mg/kg every 2 weeks (Q2W) or placebo Q2W (5% dextrose in water).

Results

• A total of 68 patients were randomized to treatment, of which 57 patients completed study treatment through day 57.
• Mild dose-dependent and reversible elevations of cholesterol, LDL and HDL were seen with nipocalimab (see Table: Mean Change from Baseline in Total Cholesterol, LDL, and HDL).
  • The maximum mean percent increase in cholesterol to HDL ratio was <5% for all the nipocalimab groups.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 January 2025.