FDA Halts Clinical Studies of Magrolimab in AML, MDS


Magrolimab will no longer be in development as a treatment option for patients with hematologic malignancies.

Blood Cancer: © Hadi - stock.adobe.com

Blood Cancer: © Hadi - stock.adobe.com

  • All studies of magrolimab (Hu5F9-G4) in hematologic malignancies, including expanded access programs, have been placed on full clinical hold by the FDA.
  • Gilead Sciences has halted all its studies of magrolimab in hematologic malignancies and will not pursue the drug’s development in this patient population.
  • Magrolimab demonstrated futility and increased the risk of death in this population, according to an independent data monitoring committee.

The phase 3 ENHANCE-3 (NCT05079230) study of magrolimab, a first-in-class anti-CD47 monoclonal antibody for the treatment of acute myeloid leukemia (AML), has been stopped, and the FDA has placed all studies of magrolimab in AML and myelodysplastic syndromes (MDS) on full clinical hold.1

An independent data monitoring committee found that magrolimab demonstrated futility and an increased risk of death, primarily by infection and respiratory failure. Gilead, the manufacturer of magrolimab, will no longer pursue the development of magrolimab as a therapy for hematologic malignancies. The full clinical hold also applies to the expanded access program for magrolimab in patients with relapsed/refractory AML (NCT05627466).

This follows the partial clinical hold that the FDA put in place on magrolimab in AML in August 2023. In September 2023, the phase 3 ENHANCE-2 trial (NCT04778397) of magrolimab in patients with AML and TP53 mutations was also was discontinued due to futility. Analyses from ENHANCE-2 and ENHANCE-3, as well as the phase 3 ENHANCE study (NCT04313881) of magrolimab plus azacytidine in MDS, showed futility and increased risk of death.

“The complexity of treating blood cancer is highlighted in these results,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in a press release. “We are incredibly grateful to all the patients and investigators for their participation in the ENHANCE studies.”

Magrolimab is being investigated in several studies across solid tumor types, and its safety in these trials will be reviewed. These trials include the phase 1 PNOC025 (NCT05169944) of magrolimab in pediatric and adult patients with progressive brain tumors,2 the phase 2 ELEVATELung&UC study (NCT04827576) in non–small cell lung cancer and urothelial carcinoma (UC),3 and the phase 1 MACOCUC-01 study (NCT05738161) of magrolimab plus chemotherapy in UC.4

The phase 1 National Cancer Institute-sponsored study (NCT04751383) of magrolimab and dinutuximab (Unituxin) in patients with relapsed/refractory neuroblastoma or relapsed osteosarcoma, which began enrolling patients in 2021, was suspended due to unacceptable toxicities.5

Top-line data from all 3 ENHANCE trials is expected to be shared, and more details will be revealed at upcoming medical conferences.1

1. Gilead statement on discontinuation of phase 3 ENHANCE-3 study in AML. News release. Gilead Sciences. February 7, 2024. Accessed February 7, 2024. http://tinyurl.com/nhaj7mk7
2. Magrolimab in children and adults with recurrent or progressive malignant brain tumors (PNOC025). ClinicalTrials.gov. Updated January 17, 2024. Accessed February 7, 2024. https://clinicaltrials.gov/study/NCT05169944
3. Study of magrolimab in patients with solid tumors (ELEVATELung&UC). ClinicalTrials.gov. Updated December 18, 2023. Accessed February 7, 2024. https://clinicaltrials.gov/study/NCT04827576
4. Magrolimab in combination with cytotoxic chemotherapy in advanced urothelial carcinoma (MACOCUC-01). ClinicalTrials.gov. Updated July 5, 2023. Accessed February 7, 2024. https://clinicaltrials.gov/study/NCT05738161
5. Testing the combination of two immunotherapy drugs (magrolimab and dinutuximab) in patients with relapsed or refractory neuroblastoma or relapsed osteosarcoma. ClinicalTrials.gov. Updated January 17, 2024. Accessed February 7, 2024. https://www.clinicaltrials.gov/study/NCT04751383
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