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 24-week, phase 3, randomized, double-blind, placebo-controlled trial in adult patients with gMG, headache was reported in 14.3% of patients in the nipocalimab group and 17.3% of patients in the placebo group.¹
• In a phase 2, randomized, double-blind, placebo-controlled trial in adult patients with gMG, headache was reported in 11.1% of patients in the combined nipocalimab group and in 7.1% of patients in the placebo group through day 113.^2,4 
• In an ongoing, phase 2/3, open-label, uncontrolled clinical trial in adolescents (12 to <18 years of age), headache was reported in 14.3% of patients on nipocalimab treatment through week 24.^3,5

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 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.
• Headache was reported in 14.3% (14/98) of patients in the nipocalimab group and in 17.3% (17/98) of patients in the placebo group.

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.
• The study consisted of a 4-week screening period, followed by an 8-week, double-blind treatment period. Post treatment follow-up assessment was over a 8 week period.
• 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).

Results

• A total of 68 patients (nipocalimab, n=54; placebo, n=14) were randomized to treatment.
• Through day 113, headache was reported as treatment-emergent adverse event in 11.1% (6/54) of patients in the combined nipocalimab group and in 7.1% (1/14) of patients in the placebo group.^2,4 
  • In patients treated with nipocalimab, headache was reported in 14.3% (2/14) of patients in 5 mg/kg Q4W group, 7.7% (1/13) of patients in the 30 mg/kg Q4W group, 15.4% (2/13) of patients in the 60 mg/kg single dose group and 7.1% (1/14) of patients in the 60 mg/kg Q2W group.

Vibrance-mg Study

Ramchandren et al (2022)^5,6 is evaluating the safety, efficacy, PK, and PD of nipocalimab in children and adolescents in ages 2 to <18 years with gMG who have an insufficient response to ongoing, stable SOC therapy in an ongoing, open-label, uncontrolled multicenter clinical trial.

Study Design/Methods

• Patients with anti-AChR or anti-MuSK antibody positive gMG (MGFA Class IIa-IVb) were included in the study.
• The study consists of a screening period of up to 4 weeks, followed by a 24-week open-label active treatment phase where adolescent (12 to <18 years of age) patients will receive nipocalimab 30 mg/kg intravenous loading dose at week 0 followed by 15 mg/kg Q2W from week 2 to 22 in addition to SOC. Patients will have the option to enroll in an long-term extension phase.
  • A safety follow-up assessment will be conducted 8 weeks after the last dose.

Results

Strober et al (2024)³ 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.

• Seven adolescent patients, all with anti-AChR antibody positive gMG were included in the analysis.
• Headache was reported in 1 patient (14.3%) through week 24.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 November 2024.