Gilead's $4.9B CD47 bet faces latest setback as company cans MDS ambitions for magrolimab

Gilead Sciences' $4.9 billion bet on Forty Seven has run into further trouble, with the Big Pharma pulling the plug on its myelodysplastic syndromes (MDS) ambitions for the lead CD47 asset from that deal in the face of a disappointing phase 3 trial.

The ENHANCE study had randomized over 500 patients with higher-risk MDS to either receive either its anti-CD47 antibody magrolimab in combination with Bristol Myers Squibb’s Vidaza or Vidaza alone. But Gilead announced in a post-market release Friday that it had discontinued the study due to futility after taking a look at the results of a planned analysis. The primary endpoints were complete response and overall survival.

As a result, the company said it now “recommends discontinuing treatment with magrolimab in patients with MDS” and is working with study investigators on “appropriate next steps for patients enrolled in the ENHANCE study.”

The Big Pharma is still assessing the antibody in many other cancer indications, including two “pivotal” phase 3 trials: the ENHANCE-2 study in acute myeloid leukemia (AML) with TP53 mutations; and the ENHANCE-3 study in first-line, unfit AML.

“The health and wellbeing of patients are our top priorities and while this is disappointing news it confirms the challenges of treating HR-MDS, where no new class of treatments have been approved in nearly 20 years,” said Gilead’s Chief Medical Officer Merdad Parsey, M.D., Ph.D., in the release. “Gilead is deeply grateful to the patients, families, investigators, and the advocacy community who contributed to this research as we learn more about magrolimab and explore its potential in treating other cancers.”

Magrolimab is a monoclonal antibody targeting CD47, a protein that supports tumor proliferation and growth. The hope is that by limiting the receptor, the body’s macrophages can clear out tumorous cells that may otherwise spread.

Gilead acquired magrolimab as part of its $4.9 billion acquisition of Forty Seven back in 2020. However, the antibody has had a bumpy ride through the clinic, with a number of trials placed on hold by the FDA last year due to adverse reactions. Gilead noted today that while the trial had failed on futility, the “safety data seen in this study is consistent with the known magrolimab profile and adverse events that are typical in this patient population.”

The company can at least take solace in the fact it is not the only pharma to struggle in the CD47 space. In August last year, AbbVie pulled out of a partnership with I-Mab to assess its candidate lemzoparlimab. That same month, Zai Lab cited “the competitive landscape” as the reason for deprioritizing internal development of its monoclonal antibody ZL-1201.