IMAAVY - Effect on Minimal Symptom Expression in Patients with Generalized Myasthenia Gravis

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• In a phase 3, 24-week, randomized, double-blind (DB), placebo (PBO)-controlled trial with an open-label extension (OLE) in adult patients with generalized myasthenia gravis (gMG)¹:
  • A total of 10% (8/77) of patients treated with IMAAVY achieved minimal symptom expression (MSE) at ≥75% of all DB-phase timepoints. 
  • In a post-hoc analysis, 23.4% of patients in the IMAAVY group achieved MSE at week 22, 23, and 24 compared to 6.6% of patients in the PBO group (OR, 4.3 [95% CI, 1.5-12.4]).²
  • In another post-hoc analysis, patients in the IMAAVY group were more likely to reach and sustain MSE by week 24 than patients in the PBO group (OR [odds ratio] 2.68 and 4.35, respectively).³
  • In an interim analysis of the OLE data, 32% of patients reached sustained MSE for ≥8 weeks.⁴

Clinical data

VIVACITY-MG3

Antozzi et al (2025)¹ evaluated the efficacy and safety of IMAAVY in adults with gMG in a phase 3 (VIVACITY-MG3), randomized, multicenter, DB, PBO-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-related protein 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.^1,5
  • The primary efficacy analysis population included all patients from the safety analysis dataset who were antibody-positive for AChR, MuSK, or LRP4, confirmed prior to randomization.¹ 
• The study consisted of a ≤4-week screening phase, followed by a 24-week, DB, PBO-controlled treatment phase, a variable-duration OLE phase, and safety follow-up at 8 weeks after the last infusion.^1,6 
• Eligible patients were randomized (1:1) to receive a loading dose of intravenous (IV) IMAAVY 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.¹ 
• Patients entering the OLE phase continued to receive IMAAVY 15 mg/kg Q2W in addition to SOC.^1,7 
• The primary efficacy endpoint was the average change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score over weeks 22, 23, and 24.¹ 
• Other prespecified endpoints included the percentage of patients who were antibody-positive who reached MSE (defined as MG-ADL total score of 0 or 1) at any time during the DB phase, and the percentage of patients maintaining MSE at 75% of all timepoints through the double-blind phase.

Results

• A total of 199 patients were randomized, and 196 patients (98 in each treatment group) received at least 1 dose of study drug. Of those patients, 153 patients were included in the primary efficacy analysis set (all antibody positive patients only). See Table: Baseline Demographics and Characteristics.

MG-ADL Score

• Through weeks 22 to 24, a greater reduction in the MG-ADL total score from baseline was observed in the IMAAVY group (Least square mean [LSM change], -4.70 [standard error (SE), 0.329]) vs PBO group (LSM change, -3.25 [SE, 0.335]). The difference in the total MG-ADL score between IMAAVY and PBO was -1.45 (95% confidence interval [CI], -2.38 to -0.52; P=0.0024).

MSE

• During the DB phase, 31% (24/77) of patients receiving IMAAVY reached MSE at least once, compared with 13% (10/76) of patients in PBO group. Additionally, 10% (8/77) of patients treated with IMAAVY reached MSE at ≥75% of all DB-phase timepoints, versus 1% (1/76) of patients receiving PBO.
• Vu et al (2026)² conducted a post hoc analysis of the VIVACITY-MG3 study to evaluate the effect of IMAAVY on MSE during the DB phase.

Results

• A total of 23.4% of patients in the IMAAVY group achieved MSE at week 22, 23, or 24 compared to 6.6% of patients in the PBO group (OR, 4.3 [95% CI, 1.5-12.4]).
• Of the 25 patients (IMAAVY, n=18; placebo, n=7) who achieved MSE at ≥2 consecutive visits, patients in the IMAAVY group spent more of their time with MSE compared to PBO (60.4% vs 32.7%).
• A greater proportion of patients on IMAAVY achieved sustained MSE for ≥8 weeks compared to placebo as shown in Table: Patients Achieving Sustained MSE.

Vincente et al (2026)³ conducted a post hoc analysis of the VIVACITY MG-3 study to evaluate MSE treatment response and quality of life (QoL) in patients who attained sustained versus transient MSE during the DB phase.

Study Design/Methods

• The analyses were performed using the prespecified efficacy analysis set of seropositive patients who received ≥1 dose of study intervention in the DB phase.
• Patients were classified based on the MSE status into:
  • No MSE: Never achieved MSE
  • Transient MSE: Achievement of MSE at least once, but not sustained for ≥8 weeks
  • Sustained MSE: Achievement of MSE that was sustained ≥8 weeks.
• The study assessments included the following:
  • Proportion of patients achieving and sustaining MSE in IMAAVY and PBO groups
  • Odds of achieving transient or sustained MSE for IMAAVY vs PBO
  • Evaluation of the impact of MSE status on QoL, as assessed by improvement in the
    Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r) score.

Results

• The proportion of patients who reached MSE during the DB phase is shown in Table: Patients Achieving MSE by Week 24.
• Patients in the IMAAVY treatment group were more likely to reach (OR, 2.68 [95% CI, 1.20-5.96], P=0.020) and sustain MSE (OR, 4.35 [95% CI, 1.37-13.81], P=0.013) by week 24 than patients in the PBO group.
• Patients in the sustained MSE group showed greater improvements in MG-QoL-15r scores than those in the transient MSE and no MSE groups. See Table: MG-QoL-15r Improvement at Week 24.

Antozzi et al (2026)⁴ conducted an interim analysis of the VIVACITY-MG3 data to evaluate the long-term safety and efficacy of IMAAVY in patients who entered the OLE phase.

Study Design/Methods

• Patients who completed the DB phase (24 weeks) were eligible to enter the OLE phase where all patients received treatment with IMAAVY and SOC.
• Data were collected through week 96 of OLE with a data cutoff of August 2024.

Results

• In the DB phase, 153 patients with antibody-positive gMG were included in the efficacy analysis set.
• A total of 137 patients with antibody-positive gMG (71 from the IMAAVY+SOC group and 66 from the PBO+SOC group) entered into the OLE phase and were treated with IMAAVY+SOC with a follow-up duration of over 96 weeks.

MG-ADL Score

• At OLE week 96, the mean (SE) change from DB baseline in the MG-ADL total score was
  -6.47 (1.20) in the IMAAVY → IMAAVY + SOC group, -6.69 (0.85) in the PBO+SOC → IMAAVY + SOC group, and -6.58 (0.71) in the overall IMAAVY + SOC group.

MSE

• Half of the patients (50%; 77/153) reached MSE at any time during the study, including the DB and OLE phase.
  • In the DB period, 11 patients treated with PBO+SOC reached anytime MSE, and 10 of those patients continued into the OLE phase, where they were treated with IMAAVY + SOC. These 10 patients reached anytime MSE in the OLE period.⁸
• A total of 32% (49/153) of patients sustained MSE for ≥8 weeks through the DB and OLE phases.
  • In the DB period, 4 patients treated with PBO+SOC reached sustained
    MSE ≥8 weeks and continued into OLE where they were treated with IMAAVY+SOC. These 4 patients reached sustained MSE ≥8 weeks in the OLE period.⁸

Silvestri et al (2025)⁹ conducted an additional analysis of VIVACITY-MG3 to evaluate the long-term efficacy of IMAAVY + SOC in the subset of patients who received IMAAVY + SOC during both the DB and OLE phases.

Study Design/Methods

• Data were collected through week 48 (DB 24 weeks+OLE 24 weeks), with a cutoff date of August 2024.
• Study assessments included the following:
  • Proportion of patients achieving MSE, defined as an MG-ADL score of 0 or 1
  • Proportion of patients with sustained MSE for ≥8 weeks
  • Percentage of time spent in MSE, defined as the percentage of time with improvement (calculated as cumulative days of MSE divided by the number of days in the study up to OLE week 24).

Results

• A total of 71 patients from the IMAAVY + SOC group of the DB phase continued to receive IMAAVY + SOC during the OLE phase.

MSE

• Percentage of patients reaching MSE at any time during the DB phase and at week 24 was 31.2% and 22.1%, respectively.
• Overall, 33.8% of patients reached MSE at week 48 (n=23), see Figure: Proportion of Patients Achieving MSE in MG-ADL Score through Week 48.
• Sustained MSE for ≥8 weeks was reported in 31.2% of patients (n=24).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 05 June 2026.