SUMMARY

• Please refer to the local labeling for relevant information regarding effects on lipids with IMAAVY.
• In a phase 3, randomized, double-blind (DB), placebo (PBO)-controlled trial in adults with generalized Myasthenia Gravis (gMG), IMAAVY was shown to increase mean low-density lipoprotein (LDL) by 8.3%, high-density lipoprotein (HDL) by 7.0%, and total cholesterol (CHOL) by 7.8% at week 24. The mean total CHOL-to-HDL ratio was <4 over 24 weeks.¹ 
  • Within the IMAAVY group, 62 patients had LDL levels <4.1 mmol/L (<160 mg/dL) at baseline. Of these, 7 patients (11.0%) moved to an LDL level ≥4.1 mmol/L (≥160 mg/dL) to <4.9 mmol/L (<190 mg/dL) at week 24.² 
  • Seven patients (IMAAVY, n=3; PBO, n=4) were newly initiated on lipid modifying agents and had reductions in LDL levels observed at week 24 after starting lipid modifying agents.^1,2 
  • Through week 24, there were no reports of major adverse cardiovascular events (MACE) in the IMAAVY group and 3 reports in the PBO group.² 
• In the ongoing open-label extension (OLE) of the phase 3 study, in patients with seropositive gMG (n=137), the mean changes from baseline to week 60 in the CHOL-to-HDL ratios were -0.2 and 0.2 for the PBO→IMAAVY and IMAAVY→IMAAVY groups, respectively.³ 
  • Through an average follow-up duration of 70.53 weeks, there were 7 reports of non-fatal MACE and 3 reports of fatal MACE in the safety analysis population (n=176).⁴

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)^1,3,5 evaluated the efficacy and safety of IMAAVY in adults with gMG in a phase 3, randomized, multicenter, DB, PBO-controlled study with an ongoing OLE phase.

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 DB phase.
• The study consisted of a ≤4-week screening phase, followed by a 24-week, DB, PBO-controlled treatment phase, a variable-duration OLE phase (up to 240 weeks in the European Union), 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 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.
• Patients entering the OLE phase continued to receive IMAAVY 15 mg/kg Q2W in addition to SOC.
• Lipids were monitored at DB weeks 0, 4, 8, 12, and 24; at OLE screening, weeks 4, 12, and 24; then, every 12 weeks through OLE week 96 and every 24 weeks thereafter.
• In patients with elevated lipids, the study protocol recommended that investigators initiate or continue appropriate therapy for dyslipidemia as per local health guidelines.

Results

DB Phase

• A total of 196 patients (IMAAVY, n=98; PBO, n=98) were in the full analysis set.
• At week 24, the mean change from baseline was 7.8% for total CHOL, 7.0% for HDL, and 8.3% for LDL in the IMAAVY group, and was -4.1% for total CHOL, -1.6% for HDL, and –3.0% for LDL in the PBO group, with the mean total CHOL-to-HDL ratio in the IMAAVY group remaining at <4 over 24 weeks.¹ 
  • The mean (SD) change from baseline in the IMAAVY group was 14.40 (35.135) mg/dL for total CHOL, 4.52 (13.223) mg/dL for HDL, and 7.46 (28.699) mg/dL for LDL. The mean (SD) change from baseline to week 24 in the PBO group was -10.30 (26.687) mg/dL for total CHOL, -2.13 (11.015) mg/dL for HDL, and -4.92 (19.280) mg/dL for LDL (see Figure: Mean (SE) Values for Lipids in DB Phase).⁵ 

• At week 24, more patients in the IMAAVY group vs the PBO group experienced shifts to a higher-risk category of LDL values (see Table: Shift from Baseline in LDL CHOL Levels at Week 24).² 
  • Within the IMAAVY group, 62 patients had LDL levels <4.1 mmol/L (<160 mg/dL) at baseline. Of these, 7 patients (11.0%) moved to an LDL level ≥4.1 mmol/L (≥160 mg/dL) to <4.9 mmol/L (<190 mg/dL) at week 24.
  • Within the PBO group, 65 patients had LDL levels <4.1 mmol/L (<160 mg/dL) at baseline. Of these, 3 patients (4.6%) moved to an LDL level ≥4.1 mmol/L (≥160 mg/dL) to <4.9 mmol/L (<190 mg/dL) at week 24.

• Seven patients (IMAAVY, n=3; PBO, n=4) were newly initiated on lipid modifying agents.^1,2 
• Mean changes from baseline in LDL in patients who did or did not start lipid modifying agents are summarized in Figure: Mean Change from Baseline for LDL (mmol/L) (SD) – Patients Who Did/Did Not Start Lipid Modifying Agent in the DB Phase.
  • Patients in both the PBO and IMAAVY arms had reductions in LDL levels observed at week 24 after starting lipid modifying agents.

• No patients discontinued study treatment due to lipid changes.
• Through week 24, there were no reports of MACE in the IMAAVY group and three reports in the PBO group.²

Ongoing Open-Label Extension

• A total of 137 patients with antibody-positive gMG entered the OLE phase.³ 
  • PBO→IMAAVY, n=66; IMAAVY→IMAAVY, n=71
  • The mean change from baseline CHOL-to-HDL ratio was -0.2 and 0.2 in the PBO→IMAAVY and IMAAVY→IMAAVY arms, respectively, at week 60 (see Figure: Lipids Over Time in the Antibody-Positive Population).

• A total of 176 patients in the OLE phase were included in the safety analysis set (average follow-up duration of 70.53 weeks)⁴ 
  • PBO→IMAAVY, n=88; IMAAVY→IMAAVY, n=88
  • There were seven reports of adjudicated non-fatal MACE in one patient, and three reports of adjudicated fatal MACE in three patients. Eight of these cases occurred in one patient.^4,6 

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)^7,8 conducted a phase 2, randomized, multicenter, DB,   PBO-controlled clinical trial to evaluate the safety, efficacy, PK, and 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.
• The study included a 4-week screening period, followed by an 8-week DB treatment period. Post treatment 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: 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).

Results

• A total of 68 patients were randomized to treatment, of which 57 patients completed study treatment through day 57.
• Mild dose-dependent and reversible elevations of CHOL, LDL and HDL were seen with IMAAVY (see Table: Mean Change from Baseline in Total CHOL, LDL, and HDL).
  • The maximum mean percent increase in CHOL-to-HDL ratio was <5% for all the IMAAVY groups.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 28 May 2025.