IMAAVY - Pharmacokinetics and Pharmacodynamics in Patients with Generalized Myasthenia Gravis

SUMMARY

• Please refer to the local labeling for relevant information regarding the pharmacokinetics (PK) and pharmacodynamics (PD) of IMAAVY.
• In a phase 3, randomized, double-blind, placebo (PBO)-controlled trial, the median predose reduction from baseline in the total serum immunoglobulin G (IgG) after the loading dose was -74.6% at week 2 and -68.8% at week 24 in the IMAAVY 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 IMAAVY and PBO groups, respectively.
  • In the ongoing open-label extension (OLE) of the study, the mean predose (minimal) percent change from baseline (CFB) in the IgG level was -64.06 in the IMAAVY→IMAAVY + standard of care (SOC) group and -63.24 in the PBO→IMAAVY + SOC group at week 96.³ 
• 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 IMAAVY infusion, ranging from 42% at 5 mg/kg dose to 69% at 30 mg/kg or higher doses.⁴
• In an ongoing, phase 2/3, open-label, uncontrolled clinical trial in adolescents (12 to <18 years of age), a reduction in median (interquartile range [IQR]) serum IgG was observed from baseline (10.7 [8.9-13.1] g/L) to week 24 (3.2 [2.3-3.5] g/L) and week 72 (3.3 [2.8-4.3] g/L).⁵

CLINICAL DATA

VIVACITY-MG3 Study

Antozzi et al (2025)² evaluated the efficacy and safety of IMAAVY in adults with generalized myasthenia gravis (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, OLE phase, and a safety follow-up at 8 weeks after the last infusion.^1,2,6 
  • Patients who withdrew or discontinued after receiving any amount of the study intervention were required to complete a safety follow-up visit at 8 weeks after the last dose.
• Eligible patients were randomized (1:1) to receive either a loading dose of intravenous (IV) IMAAVY 30 mg/kg at week 0, followed by IV IMAAVY 15 mg/kg every 2 weeks (Q2W) or matching PBO through week 24 in addition to SOC therapy.
• Patients entering the OLE phase continued to receive IMAAVY 15 mg/kg Q2W in addition to SOC.³ 

Results

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

Pharmacodynamic Activity

• In the full analysis set, the median predose (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 IMAAVY group.²
• In the ongoing OLE, at week 96, the mean (standard deviation) predose (minimal) percent change from double-blind baseline in the IgG level was -64.06 (12.91) in the IMAAVY→IMAAVY + SOC group and -63.24 (14.32) in the PBO→IMAAVY + SOC group. See Figure: Total IgG Reduction from DB Baseline (Seropositive Population).³

• No changes in total IgM, IgA, or IgE were observed during the double-blind phase.²
• The IMAAVY group showed greater median predose reductions in anti-AChR (-65.1% vs -10.1%) and anti-MuSK (-38.8% vs -4.4%) antibody titers compared to the PBO group, respectively.¹See Table: Percent Change in Pathogenic IgG from Baseline to Week 24.

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)⁴ conducted a phase 2, randomized, multicenter, double-blind, PBO-controlled clinical trial to evaluate the safety, efficacy, PK, and PD of IMAAVY in adult patients with gMG who had an inadequate 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 IV infusions of IMAAVY 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 efficacy endpoint was CFB to day 57 in the total Myasthenia Gravis Activities of Daily Living (MG-ADL) score. The primary safety endpoint was the incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events (AEs) of special interest.
• Exploratory endpoints included PD activity of IMAAVY 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 were randomized to receive IMAAVY (n=54) or PBO (n=14).
• For baseline demographics, see Table: Baseline Demographic Characteristics (ITT Population).

PK/PD Activity

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

• Posttreatment serum samples from 54 patients treated with IMAAVY were evaluated for antidrug antibodies (ADAs). The incidence of ADA through day 113 (16 weeks) in the IMAAVY- and PBO-treated groups was reported in 22 (40.7%) patients and 1 (7.1%) patient, respectively.
  • Comparisons of median serum IMAAVY or medium serum IgG concentrations between ADA-positive and ADA-negative patients over time showed that the presence of ADA did not affect the PK or IgG lowering of IMAAVY.
• Overall, 8 (14.8%) patients in the IMAAVY group were positive for neutralizing antibodies (NAbs).
  • The incidence of NAb was too low to assess its effect on PK or PD.

Vibrance-mg Study

Ramchandren et al (2022)^7,8 is evaluating the safety, efficacy, PK, and PD of IMAAVY 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. Cohort 1 will consist of adolescents (aged 12 to <18 years), and cohort 2 will consist of children (aged 2 to <12 years).

Strober et al (2025)⁵ presented results from cohort 1 through the active treatment (AT) phase (study day 1 through week 24) and long-term extension (LTE) phase with a clinical cutoff date of August 23, 2024.

Study Design/Methods

• Adolescent patients, all with anti-AChR antibody positive gMG, were included in this analysis.
• The study consists of a screening period of up to 4 weeks, followed by a 24-week, open-label, AT phase, an optional 48-week LTE 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.
• All patients will receive an IMAAVY 30 mg/kg IV loading dose at week 0, followed by IMAAVY 15 mg/kg Q2W from week 2 to week 22 in addition to SOC therapy.
• Patients entering the LTE phase will receive IMAAVY 15 mg/kg Q2W or IMAAVY 30 mg/kg Q4W (dosing at investigator’s discretion) in addition to SOC.
• The primary efficacy endpoint is the effect of IMAAVY on the total serum IgG level at week 24.

Results

Baseline Demographics

• Baseline demographics of the 8 adolescent patients (all with anti-AChR antibody-positive gMG) are summarized in Table: Baseline Demographics and Disease Characteristics.

Efficacy

• IgG reduction was observed in adolescent patients treated with IMAAVY.
• At the time of this analysis, of the 8 patients who had been enrolled, 7 completed the AT phase and 6 entered the LTE phase.
  • Reduction in median (IQR) serum IgG was observed from baseline (10.7 [8.9-13.1] g/L) to week 24 (3.2 [2.3-3.5] g/L) and week 72 (3.3 [2.8-4.3] g/L).
  • The median (IQR) percentage CFB was -72.6% (-79.1 to -70.1) at week 2 and -73.3% (-78.7 to -62.8) at week 24. The effect was generally sustained in the LTE, with a median (IQR) CFB of -60.6% (-72.0 to 48.8) at week 72 (n=3). For details, see Figure: Median (IQR) Total Serum IgG Levels Over Time.

Safety

• During the study, there were no reports of AEs or SAEs leading to discontinuation reported in adolescent patients receiving IMAAVY. No TEAEs leading to death or AEs of special interest were reported in the study. For details, see Table: Summary of TEAEs in AT and LTE Phases.
• One patient reported with a SAE of worsened gMG after week 72 in LTE (at week 84).
• Another patient reported an AE of influenza at ~week 30 that led to temporary treatment discontinuation.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 23 September 2026.