July 21 Quick Takes: Gilead drops CD47 lead indication due to futility 

Gilead Sciences Inc. (NASDAQ:GILD) said it is discontinuing its Phase III ENHANCE study of anti-CD47 mAb magrolimab plus azacitidine for myelodysplastic syndromes (MDS) after the therapy failed a planned analysis. The study randomized over 500 patients to receive magrolimab, which blocks CD47's "don't eat me" signal on tumors, plus azacitidine, a chemotherapy that increases display of calreticulin "eat me" signals, or azacitidine alone. Primary endpoints were complete response and overall survival. Data from the study will be presented at a future medical meeting, with Gilead sharing only that "the safety data seen in this study is consistent with the known magrolimab profile and adverse events that are typical in this patient population." In January 2022, FDA placed a partial clinical hold on five magrolimab combination trials due to an “apparent imbalance” in investigator-reported suspected unexpected serious adverse reactions between study arms; the hold was lifted in April 2022.

Gilead has two ongoing pivotal trials of magrolimab — the ENHANCE-2 study in acute myeloid leukemia with p53 mutations and ENHANCE-3 in first-line, unfit AML — plus earlier stage trials in other indications including solid tumors. The company gained the potential first-in-class mAb against CD47 via its $4.9 billion takeout of Forty Seven Inc. in March 2020. At least four other companies have CD47 pathway-targeting programs in development for MDS, including I-Mab Biopharma (NASDAQ:IMAB), which in April dosed the first patient in its Phase III registrational study in China of lemzoparlimab for MDS...