Fast track designation granted to magrolimab for the treatment of AML

The United States (US) Food & Drug Administration (FDA) has granted fast track designation (FDD) to magrolimab (5F9) for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).¹ This decision is based on the results of the phase Ib trial, 5F9005 (NCT03248479), presented during the 24^th Annual Congress of the European Hematology Association (EHA). This study was the first to combine an anti-CD47 agent with a hypomethylating agent. Key data from this presentation, and an expert interview with David Sallman, can be found below.¹

About magrolimab and the founding study^1,2

• Magrolimab is a first-in-class anti-CD47 monoclonal antibody (mAb) that aims to block the signal from the SIRPα receptor on macrophages to induce phagocytosis
• Azacitidine synergizes with magrolimab, inducing pro-phagocytic signals in AML and enhancing the phagocytic effect
• The 5F9005 study was a phase Ib study of 34 patients with AML or MDS
• Patients with previously untreated AML, eligible for induction therapy (n= 15), and patients with untreated, intermediate to high-risk MDS (n= 9), received magrolimab plus azacitidine
• Median age: 73 years
• Doses:
  • Escalating doses of weekly magrolimab were given, starting at a priming dose of 1mg/kg and increasing to 30mg/kg
  • Azacitidine: 75mg/m² days 1–7
• Safety results for the magrolimab plus azacitidine combination therapy:
  • The maximum tolerated dose (MTD) was not reached
  • Magrolimab did not increase azacitidine toxicities
  • Treatment-related adverse events (TRAEs) occurring in >10% of patients:
    • Anemia: 25%
    • Thrombocytopenia: 20%
    • Infusion reactions: 15%
• Efficacy results in patients treated with the combination therapy:
  • Magrolimab plus azacitidine combination therapy (n=15; given as AML vs MDS: 10 vs 5):
    • Complete response (CR) or CR with incomplete blood count recovery (CRi): 53% (n= 8, 5 vs 3)
    • As of January 2019, no relapses were observed in responders
      • Median follow-up of 3.4 months
    • Median time to response: 1.9 months
• In a separate group of patients with relapsed/refractory (R/R) AML (n= 6) or MDS (n= 4) magrolimab was administered as monotherapy. One patient had a response achieving a morphologic leukemia-free state (MLFS)
• An expansion cohort is ongoing (NCT03248479)