SUMMARY

• Nipocalimab is an investigational, fully human, high-affinity, aglycosylated, effectorless immunoglobulin G1 (IgG1) antineonatal 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
  • The crystal structure of nipocalimab fragment antigen-binding (Fab) in complex with FcRn demonstrates its unique binding epitope to the FcRn immunoglobulin G-binding site on the FcRn. The crystal structure indicates that nipocalimab Fab has a low likelihood of steric hindrance or allosteric modulation of the albumin-binding site.⁴ 
• In a 24-week phase 3, randomized, double-blind, placebo-controlled trial in adult patients with gMG, hypoalbuminemia (<2 g/dL) was not reported in the nipocalimab or placebo group.¹
• In a phase 2, randomized, double-blind, placebo-controlled trial in adult patients with gMG, mild dose-dependent decreases from baseline in mean serum albumin levels were reported in the nipocalimab groups. Overall, mean serum albumin concentrations remained within normal limits (3.5-5.5 g/dL) throughout the treatment and follow-up periods for all the nipocalimab groups.²
  • There were no reports of grade 3 hypoalbuminemia as an adverse event of special interest (AESI) through day 113.^2,5

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 (Myasthenia Gravis Foundation of America [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 either a loading dose of intravenous nipocalimab 30 mg/kg at week 0 followed by 15 mg/kg every 2 weeks (Q2W) 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.
• No cases of hypoalbuminemia (albumin <2 g/dL) were reported in either the nipocalimab or placebo groups.

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)² 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.² 
• Patients with albumin levels outside the normal range were excluded from 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.² 
• 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), nipocalimab 30 mg/kg Q4W, nipocalimab 60 mg/kg single dose, nipocalimab 60 mg/kg Q2W, or placebo Q2W (5% dextrose in water).² 
• Safety was evaluated based on treatment-emergent adverse events and grade 3 or higher hypoalbuminemia (albumin <2 g/dL) was considered an AESI.

Results

• A total of 68 patients (nipocalimab, n=54; placebo, n=14) were randomized to receive treatment.²
• Mild, dose-dependent reductions from baseline in mean serum albumin levels were observed across the nipocalimab groups, with concentrations remaining within the normal range of 3.5-5.5 g/dL throughout the study and follow-up periods (see Figure; Mean ±Standard Error [SE] Change from Baseline to Day 113 in the Serum Albumin Level).^2,6
  • In the nipocalimab 60 mg/kg Q2W group, the mean albumin reduction was -0.83 g/dL at day 57, (baseline mean albumin concentration, 4.34 g/dL; day 57 mean albumin concentration, 3.5 g/dL).² On day 113, the mean serum albumin level returned to baseline by the end of the post treatment follow-up period (day 113 mean albumin concentration, 4.8 g/dL).²
• Hypoalbuminemia as a grade 3 AESI was not reported through day 113.^2,5

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 November 2024.