Gilead ends phase 3 leukemia trial early after data disappoint, dealing another blow to $4.9B bet

Gilead Sciences' $4.9 billion immuno-oncology bet has suffered another setback. An ad hoc analysis of a phase 3 leukemia trial found the anti-CD47 antibody is unlikely to improve survival, prompting the Big Biotech to stop the study.

The candidate, magrolimab, has run into a string of problems since Gilead bought Forty Seven to add the asset to its pipeline. In the past two months alone, Gilead has stopped a phase 3 trial in myelodysplastic syndromes (MDS) in the face of lackluster interim efficacy data and reported a partial clinical hold on late-stage studies in acute myeloid leukemia (AML). 

Now, Gilead has stopped one of its phase 3 AML studies altogether. The trial, ENHANCE-2, was testing magrolimab in AML patients with TP53 mutations, genetic changes associated with treatment resistance. After an ad hoc analysis and review by an independent data monitoring committee, Gilead concluded its drug candidate plus azacitidine is unlikely to improve on the survival provided by standard of care.

The discontinuation means two of Gilead’s three attempts to get magrolimab to market in AML and MDS have flamed out in quick succession. The third attempt is testing magrolimab as a first-line treatment for unfit AML. Gilead paused enrollment in the trial last month, but work is continuing within the constraints of the partial hold. 

While Gilead is running out of opportunities to validate magrolimab in AML, its decision to commit to a broad development program means it still has other shots on goal. The biotech is testing the anti-CD47 antibody in combination with other treatments in multiple myeloma and diffuse large B-cell lymphoma, although that work is still in phase 2, and is also assessing the candidate in solid tumors. 

The FDA exempted the solid tumor studies from the partial clinical hold it placed on magrolimab in other settings last month. Gilead is evaluating the candidate in people with triple-negative breast cancer, head and neck squamous cell carcinoma, colorectal cancer and other solid tumors in midphase clinical trials.