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.^1-4
• In a phase 3, randomized, double-blind, placebo (PBO)-controlled trial, median pre-dose reduction from baseline in total serum IgG after loading dose was -74.6% at week 2 and -68.8% at week 24 in the nipocalimab group.^1,2
  • Median predose reduction in antibody titers for anti-acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) were -65.1% vs -10.1% and -38.8% vs -4.4% for the nipocalimab and PBO groups, respectively.² 
• In a phase 2, randomized, double-blind, PBO-controlled trial, dose-dependent reductions in total serum IgG levels were seen as early as week 1 after the first nipocalimab  infusion as summarized below.³
• In an ongoing, phase 2/3, open-label, uncontrolled clinical trial in adolescents (12 to <18 years of age), the mean percent change in total serum IgG from baseline to week 24 was -68.98%.⁴

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)¹  evaluated the efficacy and safety of nipocalimab in adults with gMG in a phase 3, randomized, multicenter, double-blind, PBO-controlled study.

Study Design/Methods

• Patients (≥18 years of age) with anti- AChR, 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.^1,2 
  • 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, PBO-controlled treatment phase, a variable-duration, open-label extension phase, and a safety follow-up at 8 weeks after the last infusion (included patients who withdrew or discontinued after receiving any amount of the study intervention).^1,2,5 
• 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 PBO 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 seropositive (anti-AChR+, anti-MuSK+, or anti-LRP4+) patients with gMG.^1,2 

Results

• Overall, 196 patients (nipocalimab, n=98; PBO, n=98) were included in the safety analysis set.^1,2 
  • Of those patients, 153 patients were included in the primary efficacy analysis set (all antibody positive patients only).
• For baseline demographics, see Table: Baseline Demographics and Characteristics.^1,2 

Efficacy

• The average (least square [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 PBO was -4.70 (standard error [SE], 0.329) vs
  -3.25 (SE, 0.335) (difference in LS means [SE], -1.45 [0.470]; confidence interval [CI], -2.38 to -0.52; P=0.0024).^1,2 
• The median pre-dose (minimal) reduction in the total serum IgG from baseline after loading dose was -74.6% (IQR, -79.4 to -68.7) at week 2 and -68.8%
  (IQR, -75.3 to -62.2) at week 24 in the nipocalimab group (See Figure: Median Percent Change in IgG from Baseline Through Week 24).¹ 

• The median percent change in serum IgG subclass from baseline to week 24 is presented in Table: Median Percent Change in IgG Subclass from Baseline at Week 24.⁵ 

• No changes in total IgM, IgA, or IgE were observed.
• The nipocalimab group showed a ~7-fold and ~9-fold greater median pre-dose reduction in anti-AChR (-65.1% vs -10.1%) and anti-MuSK (-38.8% vs -4.4%) antibody titers compared to the PBO group, respectively.See Table: Percent Change in Pathogenic IgG from Baseline to Week 24.² 

Safety

• The proportion of patients who reported any adverse event (AE) was 84% in both the nipocalimab (82/98) and PBO (82/98) groups.¹ 
• Serious adverse events (SAEs) were reported in 9% (9/98) and 14% (14/98) of patients in the nipocalimab and PBO group, respectively.
• The most common adverse events occurring in ≥10% of patients in the nipocalimab group compared to the PBO group were headache (14% vs 17%), muscle spasms (12% vs 3%), myasthenia gravis worsening (12% vs 12%), COVID-19 associated AE (15% vs 12%) and peripheral edema (11% vs 0%).

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)^3,6 conducted a phase 2, randomized, multicenter, double-blind, PBO-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 PBO Q2W (5% dextrose in water).
• The primary safety endpoint was incidence of treatment-emergent adverse events (TEAEs), including SAEs and AEs of special interest. The primary efficacy endpoint was change from baseline to day 57 in the total MG-ADL score.
• A secondary endpoint of the study included the correlation between change in total MG-ADL score and total serum IgG reduction from baseline.
• Exploratory endpoints included PD activity of nipocalimab as measured by changes in concentrations of total IgG, IgG subclasses, IgA, IgM, and IgE, and autoantibodies (anti-AChR and anti-MuSK).

Results

• A total of 68 patients (nipocalimab, n=54; PBO, n=14) were randomized to treatment.
• For baseline demographics, see Table: Baseline Demographic Characteristics (ITT Population).

Efficacy

• A statistically significant linear trend, indicating a positive dose-response, was observed for the primary efficacy endpoint at day 57 in the MG-ADL score (P=0.03) across the PBO, nipocalimab 5 mg/kg Q4W, 30 mg/kg Q4W, and 60 mg/kg Q2W groups.
• Patients with a greater decrease in IgG levels tended to exhibit greater reductions in the MG-ADL total scores.
  • Single dose administration of nipocalimab 60 mg/kg, which assessed durability of effect with maximal IgG reduction, showed large reductions in MG-ADL total scores through day 29 (mean [standard deviation; SD] change from baseline: -3.9 [1.32]); the magnitude of reduction decreased thereafter (mean [SD] change from baseline at day 57: -1.5 [2.82]).

Pharmacodynamics

• Dose-dependent reductions in serum total IgG levels were observed with nipocalimab.
  • Maximum IgG reductions observed in the nipocalimab 5 mg/kg Q4W, 30 mg/kg Q4W, 60 mg/kg single-dose, and 60 mg/kg Q2W groups were 42%, 72%, 80%, and 83%, respectively.
  • Mean total IgG reductions from baseline were seen as early as 1 week after the first nipocalimab infusion, ranging from 42% at 5 mg/kg dose to 69% at 30 mg/kg or higher doses.
• Similar reductions were observed with all IgG subclasses, with no changes in total IgM, IgA, and IgE across the nipocalimab treatment groups.
• Dose-dependent reductions in anti-AChR autoantibodies were seen across the nipocalimab treatment groups, corresponding to reductions in total IgG. See Figure: Mean Percentage Change in Baseline IgG and AChR-Binding Antibody by Dosing Arm Over Time.

Safety

• The proportion of combined nipocalimab-treated patients with TEAEs (83.3%) was comparable to that of PBO-treated patients (78.6%).
  • No correlation was found in the overall incidence of TEAEs among the 4 nipocalimab dose regimens or for any individually reported preferred terms.
  • All TEAEs in the nipocalimab-treated group were mild or moderate (grade 1 or 2).
  • The most frequent TEAEs reported across all groups were headache, nasopharyngitis, and diarrhea (11.1% each).
• No grade 3 adverse events of special interest (AESIs) related to infection or hypoalbuminemia were reported.

Vibrance-mg Study

Ramchandren et al (2022)^7,8 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, 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 IV loading dose at week 0 followed by nipocalimab 15 mg/kg IV Q2W from week 2 to week 22 in addition to SOC therapy. 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 is the effect of nipocalimab on the total serum IgG level at week 24.

Results

Strober et al (2024)⁴  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.

Baseline Demographics

Baseline demographics of the 7 adolescent patients (all with anti-AChR antibody-positive gMG) are summarized in Table: Baseline Demographics and Disease Characteristics.

Efficacy

• The primary efficacy endpoint analysis was conducted in 5 adolescent patients who received ≥1 dose of nipocalimab and had ≥1 post-infusion sample evaluable for the serum IgG level at the time of clinical cutoff.
• The mean percent change in the total serum IgG from baseline to week 24 was -68.98% (SE, 7.561; 95% confidence interval, -78.4 to -59.6).
• The median predose (minimal) total serum IgG reduction from baseline to week 2 and 24 was -72% and -69.87%, respectively.

Safety

• Through week 24, there were no reports of SAEs, AEs leading to discontinuation or AEs of special interest observed in adolescent patients receiving nipocalimab.
  • Patients with ≥1 AE was observed in 5 (71.4%) patients.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 09 February 2025.