SUMMARY

• The crystal structure of IMAAVY fragment antigen-binding (Fab) in complex with FcRn demonstrates its unique binding epitope to the FcRn immunoglobulin G-binding site on the FcRn. The crystal structure indicates that IMAAVY Fab has a low likelihood of steric hindrance or allosteric modulation of the albumin-binding site.¹ 
• In a 24-week phase 3, randomized, double-blind, placebo (PBO)-controlled trial in adult patients with generalized myasthenia gravis (gMG), albumin levels in the IMAAVY and PBO groups stayed within the normal laboratory reference range.²
• In a phase 2, randomized, double-blind, PBO-controlled trial in adult patients with gMG, mild dose-dependent decreases from baseline in mean serum albumin levels were reported in the IMAAVY groups. Overall, mean serum albumin concentrations remained within normal limits (3.5-5.5 g/dL) throughout the treatment and follow-up periods for all the IMAAVY groups.³
  • There were no reports of grade 3 hypoalbuminemia as an adverse event of special interest (AESI) through day 113.^3,4

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)² evaluated the efficacy and safety of IMAAVY 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- 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 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.
  • 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 either a loading dose of intravenous 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.

Results

• A total of 196 patients (IMAAVY, n=98; PBO, n=98) were included in the full analysis set.
• There was a mild decrease in albumin level in the IMAAVY group
  • At week 24, the mean percent change from baseline in albumin was –7·2% (standard deviation [SD], 5·37) and –2·1% (SD, 7·08) in the IMAAVY and PBO groups, respectively.
  • However, all albumin levels stayed within the normal range.

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)³ conducted a phase 2, randomized, multicenter, double-blind, PBO-controlled clinical trial to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of IMAAVY 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.³ 
• Patients with albumin levels outside the normal range were excluded from the study.
• The study included a 4-week screening period, followed by an 8-week, double-blind treatment period. Post treatment follow-up assessment was performed for a period of 8 weeks.³ 
• In addition to SOC therapy, eligible patients were randomized (1:1:1:1:1) to receive intravenous infusions of IMAAVY 5 mg/kg once every 4 weeks (Q4W), IMAAVY 30 mg/kg Q4W, IMAAVY 60 mg/kg single dose, IMAAVY 60 mg/kg Q2W, or PBO Q2W (5% dextrose in water).³ 
• Safety was evaluated based on treatment-emergent adverse events and grade 3 or higher hypoalbuminemia (albumin <2 g/dL) was considered an AESI.

Results

• A total of 68 patients (IMAAVY, n=54; PBO, n=14) were randomized to receive treatment.³
• Mild, dose-dependent reductions from baseline in mean serum albumin levels were observed across the IMAAVY groups, with concentrations remaining within the normal range of 3.5-5.5 g/dL throughout the study and follow-up periods (see Figure; Mean ±Standard Error [SE] Change from Baseline to Day 113 in the Serum Albumin Level).^3,5
  • In the IMAAVY 60 mg/kg Q2W group, the mean albumin reduction was -0.83 g/dL at day 57, (baseline mean albumin concentration, 4.34 g/dL; day 57 mean albumin concentration, 3.5 g/dL).³ On day 113, the mean serum albumin level returned to baseline by the end of the post treatment follow-up period (day 113 mean albumin concentration, 4.8 g/dL).³
• Hypoalbuminemia as a grade 3 AESI was not reported through day 113.^3,4

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 November 2024.