SUMMARY

• Please refer to the local labeling for relevant information regarding effects on lipids with IMAAVY. The United States (US) Prescribing Information for IMAAVY does not specify required monitoring of lipids or include management recommendations for dyslipidemia.¹ 
• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• In a phase 3, randomized, double-blind (DB), placebo (PBO)-controlled trial in adults with generalized myasthenia gravis (gMG), the mean change in LDL from baseline to week 24 was 7.46 mg/dL in the IMAAVY group and -4.92 mg/dL in the PBO group.^2,3 
  • Through week 24, there were no reports of major adverse cardiovascular events (MACE) in the IMAAVY group and 3 reports in the PBO group.⁴ 
• The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA clinical guidelines provide treatment recommendations on the management of increased LDL levels as summarized below.⁵ Please refer to the guidelines for current and complete recommendations for lipid management.

Background

• Serum cholesterol and its lipoprotein carriers, which include LDL and very low-density lipoprotein (VLDL), are known risk factors for atherosclerotic cardiovascular disease (ASCVD).⁵ Notably, LDL is a key form of atherogenic cholesterol.
• Although LDL is a primary cause of atherosclerosis, other major risk factors include cigarette smoking, hypertension, dysglycemia, other lipoprotein abnormalities, and age.
• In the US, studies suggest that optimal total cholesterol levels are approximately 150 mg/dL (3.8 mmol/L), which corresponds to an LDL level of about 100 mg/dL (2.6 mmol/L).
• In particular, patients with primary severe hypercholesterolemia (LDL levels ≥190 mg/dL [≥4.9 mmol/L]) have a high lifetime risk of ASCVD.
• Lowering LDL levels with lipid-lowering agents in addition to healthy lifestyle modifications has been shown to reduce the risk of ASCVD. Lipid-lowering agents may include statins, which are considered the cornerstone of therapy, ezetimibe, bile acid sequestrants, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

CLINICAL DATA

VIVACITY-MG3

Antozzi et al (2025)^2,3,6 evaluated the efficacy and safety of IMAAVY in adults with gMG in a phase 3, randomized, multicenter, DB, PBO-controlled study with an ongoing open-label extension (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 included in the full analysis set.
• In patients who received IMAAVY, increases in LDL were observed.⁷ The mean change from baseline peaked at Week 4, then decreased and plateaued by Week 24 to a mean increase of 7 mg/dL, respectively.
• The mean (standard deviation [SD]) change in LDL from baseline to week 24 was 7.46 (28.699) mg/dL in the IMAAVY group and -4.92 (19.280) mg/dL in the PBO group (see Figure: Mean (SE) Values for LDL Cholesterol in DB Phase).^2,3 

• At week 24, more patients in the IMAAVY group vs the PBO group experienced shifts to a higher-risk category of LDL values.⁴ 
  • 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.
• Overall, a lipid-lowering agent was used in 27% (n=26) and 24% (n=24) of patients in the IMAAVY and PBO group, respectively.² Of these, 7 patients (IMAAVY, n=3; PBO, n=4) were newly initiated on lipid modifying agents during the DB phase.⁴ 
• For lipid modifying agents used in ≥3% of patients in either the IMAAVY or PBO group at baseline, see Table: Most Common (≥3%) Concomitant Lipid Modifying Therapy in DB Phase.² 

• Patients on a lipid-lowering agent at baseline experienced a small change in LDL levels after initiating IMAAVY treatment (see Figure: Mean Change from Baseline in LDL (mmol/L) (SD) – Patients on Lipid Modifying Agent from Baseline in the DB Phase).⁴ 

• Newly initiated lipid modifying agents among the 3 patients in the IMAAVY group included omega-3, rosuvastatin, and simvastatin.⁴ 
  • Patients in both the PBO and IMAAVY arms had reductions in LDL levels observed at week 24 after starting lipid modifying agents (see Figure: Mean Change from Baseline in LDL (mmol/L) (SD) – Patients Who Newly Initiated Lipid Modifying Agent in the DB Phase).  

• No patients discontinued study treatment due to lipid changes.² 
• Through week 24, there were no reports of MACE in the IMAAVY group and 3 reports in the PBO group.⁴

Ongoing Open-Label Extension

• A total of 137 patients with antibody-positive gMG entered the OLE phase.⁶ 
  • PBO→IMAAVY, n=66; IMAAVY→IMAAVY, n=71
  • Similar percent increases in LDL were observed with IMAAVY in the OLE phase.
• A total of 176 patients in the OLE phase were included in the safety analysis set (average follow-up duration of 70.53 weeks)⁸ 
  • 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.^8,9 

treatment guideline recommendations

• The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA clinical guidelines provide treatment recommendations on the primary prevention of ASCVD as outlined in the figure below.⁵   

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 05 August 2025.