Another failure has occurred in Gilead Sciences’ $4.9 billion immuno-oncology wager. Following an ad hoc analysis of a phase 3 leukemia trial, it appears unlikely that the anti-CD47 antibody, magrolimab, will offer improved survival outcomes. Consequently, the prominent biotech has made the decision to halt the study. This setback represents another challenge for magrolimab, which Gilead acquired through its purchase of Forty Seven and subsequently integrated into its development portfolio.
Over the past two months, Gilead has faced a series of setbacks related to magrolimab. This includes discontinuing a phase 3 trial focused on myelodysplastic syndromes (MDS) due to underwhelming interim efficacy data, as well as encountering a partial clinical hold on late-stage studies targeting acute myeloid leukemia (AML).
Now, Gilead has terminated one of its phase 3 AML trials, ENHANCE-2, which was specifically assessing magrolimab’s effectiveness in AML patients carrying TP53 mutations—a genetic alteration associated with resistance to treatment. Following a comprehensive ad hoc analysis and review by an independent data monitoring committee, Gilead has concluded that the combination of its drug candidate and azacitidine is unlikely to outperform the current standard of care in terms of survival.
This recent discontinuation marks the failure of two out of three attempts by Gilead to bring magrolimab to market in the context of AML and MDS in quick succession. The third endeavor involves testing magrolimab as a first-line treatment for unfit AML patients. While enrollment in this trial was briefly paused last month, Gilead is actively working within the constraints of the partial hold. Despite the challenges, Gilead’s commitment to a comprehensive development program means it still has multiple opportunities to achieve success. The biotech is exploring the potential of the anti-CD47 antibody in combination with other therapies in the treatment of multiple myeloma and diffuse large B-cell lymphoma, although these investigations are currently in phase 2. Additionally, magrolimab is under evaluation in the context of solid tumors.
It’s noteworthy that the FDA has exempted the solid tumor studies from the partial clinical hold placed on magrolimab in other settings. Gilead is actively assessing the candidate’s potential in individuals with triple-negative breast cancer, head and neck squamous cell carcinoma, colorectal cancer, and various other solid tumors through midphase clinical trials. While challenges persist, Gilead remains steadfast in its pursuit of innovative oncology solutions, underscoring the resilience of its research efforts.