SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• While low-density lipoprotein receptor-related protein 4 (LRP4) antibody-positive patients were included in the Vivacity-MG3 study, they represent a small subset of the overall population studied (n=3/196) which primarily focused on a broader group of seropositive generalized myasthenia gravis (gMG) patients.¹ 
• Two patients with LRP4+ gMG were randomized to receive IMAAVY. Of these, 1 patient had efficacy data available through double-blind (DB) week 24, with a mean Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score of 13.0 at baseline, 10.0 at week 22, 8.0 at week 23, and 10.0 at week 24.² 
• One patient with LRP4+ gMG was randomized to receive placebo (PBO).  The mean   MG-ADL total score for this patient was 9.5 at baseline, 4.0 at week 22, 4.0 at week 23, and 4.0 at week 24.² 
• All 3 patients had at least 1 adverse event (AE) during the DB phase. None discontinued treatment or terminated study participation due to AEs.³ 
• Given the limited number of LRP4+ patients (n=3), any findings related to this subgroup must be interpreted with caution, and definitive conclusions cannot be established from this data.

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)¹ evaluated the efficacy and safety of IMAAVY in adults with gMG in a phase 3, 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 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.^1,4 
  • The safety analysis population included all randomized patients who received ≥1 dose (partial or complete) of either IMAAVY or PBO in the DB-phase, including antibody-positive and antibody-negative patients.¹ 
  • The primary efficacy analysis population included all patients from the safety analysis dataset who were positive for anti-AChR, anti-MuSK, or anti-LRP4 antibodies, as 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, open-label extension (OLE) phase, and a safety follow-up at 8 weeks after the last infusion.⁵ 
  • 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 IMAAVY 30 mg/kg at week 0, followed by 15 mg/kg every 2 weeks or matching PBO through week 24, in addition to standard of care (SOC) therapy.^1,5 
• The primary efficacy endpoint was the average change from baseline in the MG-ADL total score over weeks 22, 23, and 24 in patients with seropositive gMG (AChR+, MuSK+, or LRP4+). The key secondary endpoint assessed was the average change in Quantitative Myasthenia Gravis (QMG) score from baseline over weeks 22 and 24.¹ 

Results

• Overall, 196 patients (IMAAVY, n=98; PBO, n=98) were included in the safety analysis set.¹ 
  • Of these, 153 patients were included in the primary efficacy analysis set (patients who were antibody-positive only), with 77 patients randomized to receive IMAAVY and 76 patients randomized to receive PBO.
  • Of these, 3 patients were antibody-positive for LRP4+, with 2 patients randomized to receive IMAAVY and 1 patient randomized to receive PBO.

Efficacy

• In all patients with antibody-positive gMG, a significantly greater reduction from baseline in the MG-ADL total score over weeks 22, 23, and 24 was observed in patients in the IMAAVY group (least squares [LS] mean change, -4.70 [standard error (SE) 0.329]) compared to the PBO group (LS mean change, -3.25; SE, 0.335); with a difference between groups of, -1.45 (95% CI, -2.38 to -0.52; P=0.0024).^1,5 
• In a post-hoc analysis of the LRP4+ gMG subgroup, the following results were obtained:
  • MG-ADL results in patients with LRP4+ gMG (see Table: MG-ADL Mean Total Score Over the DB Phase in Patients with LRP4+ gMG)² 
  • QMG results in patients with LRP4+ gMG (see Table:  QMG Mean Total Score Over the DB Phase in Patients with LRP4+ gMG)² 
• None of the patients in the LRP4+ subgroup terminated study participation during the DB phase. However, one patient in the IMAAVY group experienced an intercurrent event (ICE) characterized as a change in gMG therapy during the DB phase. As a result of this event, this patient was excluded from the efficacy analysis⁶

Pharmacodynamics

• For pharmacodynamic outcomes in the 3 patients with LRP4+ gMG, (see Figure: Individual Percent Change from Baseline Values for Total IgG, IgG1, and IgG2 Over Time in LRP4+ Patients)

Safety

• One patient in the IMAAVY group developed a related serious AE (SAE) of herpes zoster oticus.^3,7 
• It was observed that none of the patients in either the IMAAVY or PBO group experienced any discontinuation of study treatment or termination of study participation during the DB phase.³ 

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 June 2025.