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, mean changes from baseline in the CHOL-to-HDL ratios were -0.2 and 0.2 for the PBO→IMAAVY and IMAAVY→IMAAVY groups, respectively, at week 60.³ 

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)^1,3,4 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 weeks 0, 4, 8, 12, and 24 in the study. 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).⁴ 

• 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 3 reports in the PBO group.²

Ongoing Open-Label Extension³ 

• A total of 137 patients with antibody-positive gMG entered the OLE phase.
  • PBO→IMAAVY, n=66; IMAAVY→IMAAVY, n=71
  • The median treatment duration was 69.1 weeks (range 8-128) and 62.1 weeks (range 8-128) for the PBO→IMAAVY and IMAAVY→IMAAVY groups, respectively.
• 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).

• There were 7 reports of adjudicated non-fatal MACE and 2 reports of adjudicated fatal MACE in the all-IMAAVY OLE group (average follow-up duration of 68.96 weeks); 8 of these cases occurred in one patient.^3,5

Phase 2 VIVACITY-MG Study

Antozzi et al (2024)^6,7 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 23 April 2025.