Gilead's magrolimab once again placed on partial clinical hold, another setback for Forty Seven bet

Exactly a month after Gilead Sciences revealed it had shelved a myelodysplastic syndromes (MDS) program for magrolimab, the molecule has been placed under a partial clinical hold by the FDA for its phase 3 acute myeloid leukemia (AML) studies.

The California pharma announced the regulatory action Monday morning in a brief press release that provided no details of the nature of the FDA’s concern. Gilead said the hold applies to the initiation of new patients in U.S.-based locations of magrolimab for AML as well as for the expanded access program. Patients who are already enrolled can continue receiving the therapy and will be monitored as set out in the existing study protocol.

Magrolimab was being tested in this indication in two pivotal trials: the ENHANCE-2 study in AML with TP53 mutations and the ENHANCE-3 study in first-line, unfit AML.

Gilead has informed global regulatory authorities and clinical trial investigators of the FDA’s actions. While AML is shut down for the time being, Gilead said the solid tumor program can continue without issue. Meanwhile, the company is working with regulators to figure out the next steps to release the hold and resume enrollment.

The news comes a month to the day after Gilead revealed it had canned studies in MDS for the CD47 asset, which was acquired along with Forty Seven for $4.9 billion. Gilead shut the late-stage study down for futility after getting a look at phase 3 data.

Magrolimab is a monoclonal antibody targeting CD47, a protein that supports tumor proliferation and growth. The hope is that by limiting the receptor, the body’s macrophages can clear out tumorous cells that may otherwise spread.

But, so far, the therapy has been nothing but trouble and clinical holds since it came under Gilead’s wing. The magrolimab program spent four months on ice in 2022 due to an “apparent imbalance” in adverse reactions seen in the study arms. The holds covered five studies in AML, MDS and myeloid malignancies. While the FDA lifted the block on the AML and MDS studies in April 2022, the lymphoma and multiple myeloma programs remained on hold for a few months more, according to Gilead’s second-quarter earnings release in August 2022.

When the initial hold was lifted, Gilead insisted it had confidence in the therapy’s safety profile.

“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 Chief Medical Officer Merdad Parsey, M.D., Ph.D. The company did not elaborate on why the holds were placed.