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 adult patients with gMG, 61.0% and 71.1% of patients were on concomitant corticosteroid therapy in the nipocalimab and placebo groups, respectively.¹ 
• In a phase 2, randomized, double-blind, placebo-controlled trial in adult patients with gMG, 68.5% and 78.6% of patients were on concomitant glucocorticoid therapy in the combined nipocalimab and placebo groups, respectively.² 
• In an ongoing, phase 2/3, open-label, uncontrolled clinical trial in adolescents (12 to <18 years of age), 71.4% of patients on nipocalimab treatment were on concomitant corticosteroid therapy.^3,4 

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 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 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.
• The primary efficacy endpoint was the average change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score over weeks 22, 23, and 24 in patients who were seropositive (anti-AChR, anti-MuSK, anti-LRP4) with gMG.⁵ 

Results

• Overall, 196 patients (nipocalimab, n=98; placebo, n=98) were included in the full analysis set. 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.¹ 
• A total of 61.0% and 71.1% of patients in the nipocalimab and placebo groups were on stable concomitant corticosteroid therapy, respectively (see Table: VIVACITY-MG3: Concomitant Corticosteroid Therapy).⁶ 

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)^2,7  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. Posttreatment 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 Q2W or placebo Q2W (5% dextrose in water).
• Patients were required to continue stable dosing of allowed SOC therapy including acetylcholinesterase inhibitors, glucocorticoids, or nonsteroidal immunosuppressants throughout the study unless safety issues warranted a change.
• The primary efficacy endpoint was change from baseline to day 57 in the total MG-ADL score.

Results

• A total of 68 patients (nipocalimab, n=54; placebo, n=14) were randomized to treatment.
• At baseline, 68.5% and 78.6% of patients were on concomitant glucocorticoid therapy in the combined nipocalimab group and placebo group, respectively (See Table: Baseline Corticosteroid Use in the Safety Population).⁷

Vibrance-mg Study

Ramchandren et al (2022)^4,8 is evaluating the safety, efficacy, PK, and PD of nipocalimab in children and adolescents aged 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, 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 a long-term extension phase.
  • A safety follow-up assessment will be conducted 8 weeks after the last dose.
• The primary efficacy endpoint was the effect of nipocalimab on total serum IgG at week 24.

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.
• At baseline, a total of 71.4% (5/7) adolescent patients were on concomitant corticosteroid therapy.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 October 2024.