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Fast track designation granted to magrolimab for the treatment of AML

Sep 6, 2019

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 24th 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 study1,2

  • 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)

Expert Opinion

  1. Targeted oncology. FDA Grants Fast Track Designation to Magrolimab for AML and MDS. [Accessed 2019 Sep 05]
  2. Sallman D. et al., THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY HU5F9-G4 IS ACTIVE AND WELL TOLERATED ALONE OR IN COMBINATION WITH AZACITIDINE IN AML AND MDS PATIENTS: INITIAL PHASE 1B RESULTS. 24th Congress of the European Hematology Association (EHA), Amsterdam, NL. 2019 Jun 15. Abstract #S878