In 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to magrolimab for the treatment of newly diagnosed myelodysplastic syndromes (MDS). This designation is designed to expedite the development and review of drugs for serious and life-threatening conditions, especially drugs that show potential promise over existing therapies. Over the years since, researchers posited that magrolimab could offer significant benefits to patients; after all, an initial Phase 1b study found that the treatment induced an overall response rate and complete response rate of 91% and 42% respectively. Unfortunately, the therapy and its studies have gone on somewhat of a downward trajectory.

The Discontinuance of Research

Earlier in 2023, the FDA placed a partial clinical hold on studies evaluating a combination treatment of magrolimab and azacitidine for MDS and acute myeloid leukemia (AML) due to safety concerns. The hold was lifted a few months later. But since then, reports Cancer Network, research-based biopharmaceutical company Gilead Sciences, Inc. (“Gilead”) has chosen to discontinue the Phase 3 ENHANCE study. The study planned to identify whether the combination therapy could be beneficial for people with higher-risk MDS. 

Over 500 adult participants enrolled. Participants were given one of two treatment methods—one with magrolimab and one with a placebo—for multiple treatment cycles. The goal was to understand how the treatment combination impacted complete remission rates, overall survival rates, duration of response, objective response rate, and progression-free survival (PFS). 

Some adverse reactions did occur, though researchers noted that these were common in people with higher-risk MDS. However, the trial was discontinued due to futility, or the idea that the trial lacked sufficient evidence and would not meet its original goals. To learn more about futility in clinical studies, check out this helpful journal article from JAMA. 

Gilead advises anybody who is taking magrolimab to stop using the treatment at this time. 

About Myelodysplastic Syndromes (MDS) 

Myelodysplastic syndromes refers to a group of rare blood disorders that results from abnormal and poorly formed blood cells within the bone marrow. Normally, the bone marrow produces healthy red blood cells, white blood cells, and platelets. But in MDS, these blood cells remain immature and never leave the bone marrow. This makes it harder for your body to form healthy blood cells. 

MDS can manifest in people of all ages and backgrounds, though it is more common in men and people who are older than 60. About 50% of people with MDS will see their condition progress to become acute myeloid leukemia. If you have MDS, you may experience symptoms such as:

• Anemia (low red blood cell count)
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Pale skin
• Bruising easily
• Abnormal bleeding, such as nosebleeds or bleeding from the gums
• Petechiae (flat red spots under the skin) 
• Shortness of breath
• Heart palpitations
• Fatigue and low energy
• Chest pain
• Frequent or recurrent infections, often in the lungs, sinuses, skin, or urinary tract