IMAAVY - Effect on Hemolytic and Hematologic Markers 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.
• ENERGY is a phase 2/3, multicenter, randomized, double-blind (DB), placebo (PBO)-controlled trial in adult patients with warm autoimmune hemolytic anemia (wAIHA).¹
  • Durable hemoglobin (Hgb) response was achieved in 23.7% and 21.1% of patients in the IMAAVY 30 mg/kg every 4 weeks (Q4W; P=0.015) and 15 mg/kg every 2 weeks (Q2W; P=0.044) groups respectively, compared to 7.7% of patients in the PBO group.¹
  • An increase in Hgb of ≥2 g/dL with normalization of indirect bilirubin, lactate dehydrogenase (LDH), and haptoglobin (Hp) was reported in 13.2% of patients receiving IMAAVY 30 mg/kg Q4W, 0% receiving IMAAVY 15 mg/kg Q2W, and 2.6% receiving PBO.¹
  • Among patients receiving IMAAVY 30 mg/kg Q4W who achieved a durable Hgb response, mean indirect bilirubin levels decreased by week 2 and remained below baseline during the DB phase.¹

CLINICAL DATA

Fattizzo et al (2026)¹ evaluated the efficacy and safety of IMAAVY in adults with wAIHA in an ongoing, phase 2/3 multicenter, randomized, DB, 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
  • Hgb <10 g/dL
  • Signs of hemolysis (LDH >upper limit of normal [ULN], or indirect bilirubin >ULN, or Hp <lower limit of normal [LLN])
  • Direct antiglobulin test (DAT) positive for IgG±complement component 3d (C3d)
• The study consisted of a 2-week screening phase, followed by a 24-week, DB, 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.
• Efficacy analyses were performed using the full analysis set (all randomized patients excluding 3 patients randomized to receive IMAAVY 30 mg/kg Q2W, a regimen which was subsequently discontinued).
• The safety analysis population included all randomized patients who received any dose of study treatment, which included the 3 patients who received IMAAVY 30 mg/kg Q2W.
• The primary endpoint was the proportion of patients who achieved a durable Hgb response, defined as Hgb ≥10 g/dL and a ≥2 g/dL increase from baseline for 3 consecutive visits (≥28 days) starting by week 16 without the need for rescue therapy.
• Other prespecified endpoints included normalization of hemolytic and hematologic markers (a ≥2 g/dL increase in Hgb and normalization of indirect bilirubin, LDH, Hp, and reticulocytes).¹

Results

Baseline Demographics

• A total of 118 patients were randomized of which 117 patients received any dose of IMAAVY (safety analysis population).
• The efficacy analysis population included 115 patients (IMAAVY 30 mg/kg Q4W, n=38; 15 mg/kg Q2W, n=38; PBO, n=39).
• For baseline demographics, see Table: Baseline Demographic Characteristics.

Efficacy

Primary Endpoint

• Durable Hgb response was achieved by 22.4% (17/76) in the combined IMAAVY group compared to 7.7% (3/39) in the PBO group (1-sided P=0.017).¹
  • Specifically, 23.7% (9/38) and 21.1% (8/38) of patients in the IMAAVY
    30 mg/kg Q4W (1-sided P=0.015) and 15 mg/kg Q2W (1-sided P=0.044; not significant) groups achieved durable Hgb response, respectively.

Additional Endpoints

Hemolytic and hematologic markers

• The normalization of hemolytic markers at any visit is summarized in Table: Normalization of Hemolytic Markers at Any Visit.²
• Normalization of indirect bilirubin was reported in 55.3% of patients receiving IMAAVY 30 mg/kg Q4W, 44.7% receiving IMAAVY 15 mg/kg Q2W, and 25.6% receiving PBO.¹
• An increase in Hgb of ≥2 g/dL with normalization of indirect bilirubin, LDH, and Hp was reported in 13.2% of patients receiving IMAAVY 30 mg/kg Q4W, 0% receiving IMAAVY 15 mg/kg Q2W, and 2.6% receiving PBO.
• Among Hgb responders (those achieving the primary endpoint) receiving IMAAVY 30 mg/kg Q4W, mean indirect bilirubin levels decreased by week 2 and remained below baseline throughout the DB phase.
• The mean change in indirect bilirubin levels among Hgb responders and nonresponders in the IMAAVY 30 mg/kg Q4W and 15 mg/kg Q2W groups is summarized in Figure: Mean Indirect Bilirubin in Hgb Responders and Nonresponders for IMAAVY 30 mg/kg Q4W group and Figure: Mean Indirect Bilirubin in Hgb Responders and Nonresponders for IMAAVY 15 mg/kg Q2W group.²

Safety

• Overall, treatment-emergent adverse events (TEAEs) were comparable between PBO and IMAAVY groups. The most commonly reported serious adverse event (SAE) was investigator reported wAIHA (15.8%, 5.4%, and 20.5% in IMAAVY 30mg/kg Q4W, 15mg/kg Q2W, and PBO groups, respectively). For a summary of adverse events, see Table: Summary of AEs.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 01 September 2026.