IMAAVY- Occurrence of Major Adverse Cardiovascular Events in Patients with Warm Autoimmune Hemolytic Anemia

SUMMARY

• The company cannot recommend any practices, procedures, or usage of IMAAVY that deviate from the approved labeling.
• In a 24-week, phase 2/3, randomized, double-blind, placebo (PBO)-controlled trial (ENERGY) in adult patients with warm autoimmune hemolytic anemia (wAIHA), the occurrence of major adverse cardiovascular events (MACE) was 5.4% (2/37) in the IMAAVY 15 mg/kg every 2 weeks (Q2W) group and was not reported in the IMAAVY 30 mg/kg every 4 weeks (Q4W) or PBO groups.¹

CLINICAL DATA

ENERGY Study

Fattizzo et al (2026)¹ evaluated the efficacy and safety of IMAAVY in adults with wAIHA in a phase 2/3 multicenter, randomized, double-blind, PBO-controlled study.

Study Design/Methods

• The study included adults (≥18 years of age) diagnosed with primary or secondary wAIHA for ≥3 months, defined as having all of the following:^1,2 
  • Hemoglobin (Hgb) <10 g/dL
  • Signs of hemolysis (lactic dehydrogenase [LDH] >upper limit of normal [ULN], or indirect bilirubin >ULN, or haptoglobin [Hp] <lower limit of normal [LLN])
  • Direct antiglobulin test (DAT) positive for immunoglobulin G (IgG) +/- complement component 3d (C3d)
• The study consisted of a 2-week screening phase, followed by a 24-week, double-blind, PBO-controlled treatment phase, a 144-week open-label extension (OLE) phase, and safety follow-up at 8 weeks after the last infusion.¹ 
• Eligible patients were randomized (1:1:1) to receive intravenous (IV) IMAAVY 30 mg/kg Q4W, IMAAVY 15 mg/kg Q2W, or matching PBO Q2W through week 24.
• The safety analysis population included all randomized patients who received any dose of study treatment. This included 3 patients who received IMAAVY 30 mg/kg Q2W; however, this regimen which was subsequently discontinued. 
• MACE was adjudicated by an external committee as cardiovascular death, myocardial infarction, stroke, heart failure requiring hospitalization or urgent outpatient visit, and unstable angina requiring hospitalization. 

Results

Double-Blind Phase

• A total of 117 patients (IMAAVY, n=78; PBO, n=39) were included in the safety analysis dataset.¹ 
• MACE was reported in 5.4% (2/37) of patients in the IMAAVY 15 mg/kg Q2W:¹  
  • The 2 events of MACE (cerebral ischemia, n=1; heart failure with preserved ejection fracture, n=1) were reported in 2 patients >70 years old with complex medical history.
  • Both patients later died, one due to worsening wAIHA after refusal of rescue therapy and one due to pneumonia during hospitalization. The patient who had heart failure and later died due to pneumonia during hospitalization had received 1 dose of IMAAVY prior to the event.
  • The causes of death were adjudicated to be noncardiovascular and not related to study treatment. 
  • MACE was not reported in the IMAAVY 30 mg/kg Q4W or PBO groups.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 30 August 2026.