FDA Lifts Partial Clinical Hold on Gilead’s MDS and AML Magrolimab Studies

The U.S. Food and Drug Administration lifted the partial clinical hold placed on studies evaluating Gilead Sciences’ investigational agent magrolimab in combination with azacytidine for the treatment of myelodysplastic syndrome and acute myeloid leukemia.

Photo: Merdad Parsey, chief medical officer of Gilead Sciences

The FDA removed the partial clinical hold after a review of the comprehensive safety data from each trial. Gilead, in close coordination with regulatory authorities, is planning to re-open enrollment in the magrolimab studies that were placed on a voluntary hold outside of the United States. The company is also working with the FDA regarding the remaining partial clinical hold affecting studies evaluating magrolimab in diffuse large B-cell lymphoma and multiple myeloma, two other rare cancers. The ongoing clinical studies evaluating magrolimab in solid tumors were not subject to the clinical hold.

“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,” said Merdad Parsey, chief medical officer of Gilead Sciences.

During the partial clinical hold, patients already enrolled in the affected Gilead magrolimab studies, including the pivotal, phase 3 ENHANCE study, continued receiving treatment. Prior to the trial hold, Gilead already met the pre-specified enrollment threshold required for the first interim analysis of the ENHANCE study. Based on this, Gilead is confident the readout for the first interim analysis remains on schedule for 2023.

Myelodysplastic Syndrome (MDS) is a rare, often unrecognized, under-diagnosed, bone marrow disorder widely considered to be a form of cancer. In MDS, the body’s bone marrow does not make enough mature, healthy red blood cells, white blood cells and/or platelets. While many cases may go undiagnosed, current estimates show that approximately 100,000 new cases are diagnosed each year. Therapeutic advancement for higher-risk MDS has been limited in the last 15 years and stem cell transplant is the only potential cure, but those older than 65 or with other conditions are often not eligible. One in three people with MDS will progress to AML, one of the most common types of leukemia in adults. Approximately 10,000 people die every year from AML in the United States.

Gilead acquired magrolimab with its $4.9 billion acquisition of the biotech Forty Seven two years ago. It is a potential, first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, with the goal of blocking the “don’t eat me” signal used by cancer cells to avoid being ingested by macrophages. Magrolimab is being developed in several hematologic cancers, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) as well as solid tumor malignancies. It was granted Breakthrough Therapy designation for the treatment of newly diagnosed MDS by the FDA in 2020.

Author: Rare Daily Staff