Partial Clinical Hold on Magrolimab Combo Trials for AML, MDS Lifted by FDA

The FDA has lifted its partial clinical hold on magrolimab and azacitidine studies for patients with acute myeloid leukemia and myelodysplastic syndrome.

A partial clinical placed by the FDA for magrolimab and azacitidine clinical trials in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was lifted following a comprehensive safety data review, according to a press release from Gilead Sciences.1

Following the regulatory organization’s decision, enrollment on clinical trials assessing the combination regimen can now continue. Developer Gilead noted that it will be working closely with regulatory bodied to begin re-enrollment on all of the voluntarily held magrolimab clinical trials outside of the United States. Efforts are ongoing to lift the partial clinical hold that has also been put in place for clinical trials assessing magrolimab in diffuse large B-cell lymphoma and multiple myeloma. The partial clinical hold does not impact trials evaluating the drug in solid malignancies.

“Our confidence in the risk-benefit profile of magrolimab has been unwavering, and we continue to believe in the potential for this treatment to address the unmet medical needs faced by people living with MDS and AML,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in a press release. “This is a significant milestone for Gilead and, more importantly, for patients diagnosed with these cancers. We look forward to continuing our work developing magrolimab and advancing this potential cancer treatment option.”

The partial hold on magrolimab and azacitidine was put into effect in February 2022 due to an imbalance of investigator-reported unexpected adverse effects across study arms.2 The impact of the hold was global and affected all trials featuring the combination until investigators could provide further findings. While the hold is still in effect, patients who were already enrolled on clinical trials, such as the phase 3 ENHANCE study (NCT04313881) assessing magrolimab and azacitidine vs azacitidine alone in MDS, could continue receiving treatment. The prespecified threshold for the first interim analysis had previously been met for the study. A readout for the analysis will potentially take place in 2023.

Magrolimab received a breakthrough therapy designation from the FDA for newly diagnosed MDS in September 2020.3 The designation was based on findings from a phase 1b trial that highlighted an objective response rate of 91% in 33 evaluable patients. Among these responders, 42% achieved complete remission.

References

  1. FDA lifts partial clinical hold on MDS and AML magrolimab studies. News release. Gilead Sciences. April 11, 2022. Accessed April 15, 2022. https://bit.ly/36kI3bK
  2. Gilead announces partial clinical hold for studies evaluating magrolimab in combination with azacitidine. News release. Gilead Sciences. January 25, 2022. Accessed April 15, 2022. https://bit.ly/3rSSav1
  3. Gilead’s Magrolimab, an investigational anti-CD47 monoclonal antibody, receives FDA breakthrough therapy designation for treatment of myelodysplastic syndrome. News release. Gilead Sciences. September 15, 2020. Accessed April 15, 2022. https://bit.ly/3M6B4T4