Gilead Sciences has been dealt another blow as it announces the termination of a second Phase III trial of acquired candidate magrolimab.

The company terminated the ENHANCE-2 trial (NCT04778397) in acute myeloid leukaemia (AML) with TP53 mutations.

The termination comes as a result of ad hoc analysis and a review by an independent data monitoring committee, which concluded that magrolimab is "unlikely to demonstrate a survival benefit in AML with TP53 mutations compared to standard of care".

Gilead is working with study investigators on appropriate next steps for patients enrolled in this study. This decision follows the previously announced partial clinical hold placed on the ENHANCE-2 study.

Third hit in three months

This latest termination is the third hit for Gilead with magrolimab, less than a month after the US Food and Drug Administration stopped the recruitment of AML patients in the US in August 2023. In July 2023, Gilead also terminated a Phase III trial of the candidate evaluating its efficacy and safety of magrolimab in combination with azacitidine for patients with myelodysplastic syndromes (MDS). Gilead picked up magrolimab during its acquisition of Forty Seven for $4.9bn in 2020.

Despite the latest disappointment, Gilead’s stocks have not been heavily impacted by the announcement.

In a company statement, a spokesperson added: “Gilead is deeply grateful to the patients, families, investigators and the advocacy community who participated in this trial and contributed greatly to this research. Investigators have been notified and Gilead is working with them on appropriate next steps for patients enrolled in the study.”

Clinical Trials Arena contacted Gilead Sciences for comment on its future plans with the pipeline drug but did not receive a response.

ENHANCE-2 was a randomised, open-label, Phase III trial to determine whether magrolimab plus azacitidine improved overall survival, compared with venetoclax plus azacitidine or intensive chemotherapy in previously untreated AML with TP53 mutations. Gilead reports that there were no new safety signals identified and the safety profile was comparable between treatment arms.