A final analysis of Gilead Sciences’ now-discontinued Phase III ENHANCE study showed a worrying trend of increased death risk in myelodysplastic syndromes patients treated with magrolimab.
Gilead Sciences on Friday unveiled its final analysis of the Phase III ENHANCE study, providing more details surrounding the troubled development of its blood cancer therapy magrolimab.
In the late-stage trial—which compared magrolimab against placebo in nearly 540 higher-risk myelodysplastic syndromes (HR-MDS) patients who were also receiving standard-of-care azacitidine—Gilead’s antibody resulted in an approximately 20% higher risk of death versus placebo, though this effect was not statistically significant.
Overall survival in the magrolimab arm was also shorter by approximately three months.
Magrolimab’s objective response rate was 53.7%, which was lower than the observed rate of 58.7% in placebo comparators. Median progression-free survival was also slightly shorter in magrolimab-treated patients.
In addition to missing its efficacy endpoints, magrolimab was associated with excess side effects. Grade 3 or higher treatment-emergent adverse events arose in 92.8% of treated patients, compared to 79.2% of those in the placebo group. Overall, 84.8% of adverse events were found to be related to magrolimab, and 24% of patients had to discontinue the antibody due to toxicities.
Gilead presented these data at last week’s 2024 Hybrid Congress of the European Hematology Association.
According to ENHANCE’s abstract, its results are limited by several confounding factors including the imbalance in patients eligible for transplant between groups, as well as a partial clinical hold during its enrollment. Nevertheless, these findings “highlight challenges of developing anti-CD47 therapies and other new treatments” for HR-MDS, the abstract states.
Gilead gained the rights to magrolimab from its $4.9 billion acquisition of California-based biotech Forty Seven in 2020. The monoclonal antibody, which at the time was touted to have first-in-class potential, works by targeting and binding to the CD47 protein, which is commonly highly expressed in cancer cells. Through this mechanism of action, magrolimab is designed to boost the anti-cancer activity of the immune system and enable its phagocytic players to eliminate cancer cells.
However, magrolimab’s development has run into several safety and efficacy hurdles over the years. In January 2022, the FDA placed a partial clinical hold on studies evaluating the combination of magrolimab and azacitidine after unexpected safety signals. At the time, Gilead attributed the hold to an imbalance in serious adverse reactions.
Soon after, Gilead revealed that the hold had extended to two other magrolimab studies, which did not pair it with azacitidine. The FDA lifted all clinical holds in April 2022 following a comprehensive review of its safety data.
In July 2023, Gilead announced that it had discontinued ENHANCE after a planned interim analysis satisfied the criteria for futility. In its first-quarter 2024 business report, Gilead revealed that it had terminated all of its studies of magrolimab.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
