Gilead’s Magrolimab Fails, Raises Death Risk in MDS Patients

Gilead Sciences has released the final analysis of its Phase III ENHANCE study, shedding light on the problematic development of its blood cancer therapy, magrolimab. The study, which involved nearly 540 patients with higher-risk myelodysplastic syndromes (HR-MDS) who were also receiving the standard treatment azacitidine, compared the effects of magrolimab to a placebo.

The results revealed that patients treated with magrolimab had a roughly 20% higher risk of death compared to those who received the placebo, although this difference was not statistically significant. Additionally, the overall survival for patients in the magrolimab group was about three months shorter than those in the placebo group. The objective response rate for magrolimab was 53.7%, lower than the 58.7% observed in the placebo group. Median progression-free survival was also slightly shorter for magrolimab-treated patients.

Magrolimab not only failed to meet its efficacy targets but also was linked to a higher incidence of side effects. Serious treatment-related adverse events (Grade 3 or higher) occurred in 92.8% of magrolimab-treated patients, compared to 79.2% in the placebo group. Moreover, 84.8% of the adverse events were related to magrolimab, and 24% of patients discontinued the treatment due to its toxicities.

These findings were presented at the 2024 Hybrid Congress of the European Hematology Association. The study's abstract highlighted that the results were influenced by various confounding factors, such as an imbalance in the number of patients eligible for transplant between the groups and a partial clinical hold during enrollment. Despite these limitations, the study underscores the complexities involved in developing anti-CD47 therapies and other novel treatments for HR-MDS.

Gilead acquired the rights to magrolimab through its $4.9 billion acquisition of Forty Seven, a biotech company based in California, in 2020. Magrolimab, a monoclonal antibody, was initially seen as having first-in-class potential. It works by targeting and binding to the CD47 protein, which is often overexpressed in cancer cells, thereby enhancing the immune system's ability to eliminate these cells.

However, the development of magrolimab has faced multiple challenges over the years, both in terms of safety and efficacy. In January 2022, the FDA imposed a partial clinical hold on studies evaluating the combination of magrolimab and azacitidine due to unexpected safety concerns, which Gilead attributed to an imbalance in serious adverse reactions. This hold was later extended to two additional magrolimab studies that did not involve azacitidine. By April 2022, the FDA lifted all clinical holds following an extensive review of safety data.

In July 2023, Gilead announced the discontinuation of the ENHANCE study after a planned interim analysis indicated futility. By the first quarter of 2024, Gilead had terminated all ongoing studies of magrolimab. The results from the ENHANCE study and the subsequent discontinuation of magrolimab trials highlight the significant hurdles that remain in the development of new treatments for complex conditions like HR-MDS.

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