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 subgroup analysis of a phase 3 clinical trial in adult patients with seronegative gMG, the average (least squares [LS] mean) change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) over weeks 22, 23, and 24 for nipocalimab compared to placebo was –3.3 (95% confidence interval [CI], -4.62 to -1.99) vs -3.23
  (-4.46 to-1.99) with a between group difference of -0.08 (95% CI, –1.87 to 1.71).¹ 

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. Seronegative gMG was defined as as triple-antibody negative for AChR, MuSK, or LRP4 antibodies.^1,4 
  • The safety analysis population included all randomized patients who received ≥1 dose (partial or complete) of any study treatment in the double-blind phase.¹ 
  • The efficacy analysis population included all patients from the safety analysis set who had anti-AChR, anti-MuSK or anti-LRP4 antibody positive gMG.
• 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 (IV) 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.
• The primary efficacy endpoint was the average change from baseline in the MG-ADL score over weeks 22, 23, and 24 in seropositive (anti-AChR+, anti-MuSK+, or anti-LRP4+) patients with gMG.^1,4 

Results

• Overall, 196 patients (nipocalimab, n=98; placebo, n=98) were included in the full analysis set.¹ 
  • Of those patients, 153 patients were included in the primary efficacy analysis set (antibody positive patients only) with 77 patients randomized to nipocalimab and 76 patients randomized to placebo.

Efficacy

• The average (LS mean) change from baseline in MG-ADL in patients who were antibody-positive (anti-AChR+, anti-MuSK+, or anti-LRP4+) with gMG over weeks 22, 23, and 24 for nipocalimab vs placebo was -4.7 (standard error [SE], 0.329) vs -3.25 (SE, 0.335) (difference in LS means [SE], -1.45 [0.470]; P=0.002).
• In a subgroup analysis in patients (nipocalimab, n=20; placebo, n=22) with seronegative gMG, the average (LS mean) change from baseline in MG-ADL over weeks 22, 23, and 24 for nipocalimab compared to placebo was –3.3 (95% CI, -4.62 to -1.99) vs -3.23 (-4.46 to -1.99) with a between group difference of -0.08 (95% CI, –1.87 to 1.71).

Safety

• The proportion of patients who reported an adverse event (AE) was 28.6% in both the nipocalimab (28/98) and placebo (28/98) groups.
• Serious adverse events (SAEs) were reported in 9.2% (9/98) and 14.3% (14/98) of patients in the nipocalimab and placebo group, respectively.
• The most common AEs occurring in ≥10% of patients in the nipocalimab group compared to the placebo group were headache (14.3% vs 17.3%), muscle spasms (12.2% vs 3.1%), myasthenia gravis worsening (12.2% vs 12.2%), COVID-19 (15.3% vs 10.2%) and peripheral edema (11.2% vs 0%).

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.