The FDA has suspended five clinical trials testing Gilead Sciences’ cancer drug, the centerpiece of a $4.9 billion acquisition, as the company tries to identify suspicious but undisclosed safety concerns.This Partial clinical hold This means that no new patients can be recruited, but those already enrolled in the study can continue to receive experimental cancer immunotherapies.
The drug magrolimab was added to Gilead’s pipeline in 2020 Acquired cancer drug developer47. Foster City, Calif.-based Gilead is evaluating the drug in 11 clinical trials. The partial hold affects studies testing magrolimab in combination with azacitidine, a chemotherapy drug. Three of the studies, one in myelodysplastic syndrome and two in acute myeloid leukemia, are in Phase 3 clinical trials.
According to Gilead, part of the hold stemmed from an “apparent imbalance” of unexpected serious adverse effects between the study groups. This imbalanced study was reported by clinical trial investigators without specifying. Gilead added that the partial hold covers all ongoing studies testing the magrolimab/azacytidine combination as the company gathers more data to address concerns that the FDA also did not disclose.
Magrolimab is an antibody designed to target CD47, a protein found abundantly on the surface of cancer cells. This protein sends a “don’t eat me signal”. Macrophages, immune cells that feed on pathogens, interpret this signal as a signal to keep cancer cells from leaving. By binding to CD47, magrolimab blocked the don’t eat me signal, clearing the way for macrophages to recognize and track cancer cells. While CD47-targeting drugs are still in the experimental stage, the approach is considered promising, as evidenced by major deals by Gilead and others to add such drugs to their pipelines.
Gilead said it has not seen a clear trend in adverse reactions, nor has it identified any new safety signals. If the safety signal is not new, it may be a well-known old signal from the class of CD47-targeting drugs. The challenge with targeting CD47 is that this protein is also present in red blood cells. Blocking CD47 on cancer cells also blocks CD47 on red blood cells, which are then targeted by macrophages. The result is anemia.
forty seven after testing A way to reduce the risk of anemia by using an initial dose of magrolimab. The thinking at the time was that older red blood cells expressing the CD47 protein would be targeted and eliminated, but the younger red blood cells that replaced them would not express the important signals that trigger immune cell responses and would be left alone. This approach worked in preclinical studies, and Gilead has used it in its magrolimab clinical trial, which is designed to give an initial dose followed by a maintenance dose later.
Anemia associated with targeting CD47 has led other companies to design their drugs to avoid this problem. I-Mabs are designed in a way that reduces their ability to bind to red blood cells.Shanghai-based biotech company Partners with AbbVie to develop its CD47 drug. Pfizer recently closure its Trillium Therapeutics to acquire CD47 drug developer Trillium Therapeutics for $2.3 billion. Trillium’s drug is a fusion protein that, in addition to blocking CD47, binds to macrophages through an additional “eat me” signal. In early clinical data, Trillium reported minimal binding of its drug to red blood cells.
Gilead said it will closely monitor patients already enrolled in clinical trials under the current protocol for these studies, which are currently on a partial pause. Clinical trials of magrolimab continued unaffected by partial retention in diffuse large B-cell lymphoma, multiple myeloma, head and neck squamous cell carcinoma, solid tumors, triple-negative breast cancer, and an as-yet unplanned study of colorectal cancer recruiting patients.
“The safety and well-being of those participating in our research is our top priority,” Gilead Chief Medical Officer Merdad Parsey said in a prepared statement. “We will share more information with the medical and patient community as soon as possible.”
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