Gilead’s $4.9 billion oncology bet has hit a late-phase setback. Spooked by an “apparent imbalance” in adverse reactions between study arms, the FDA has imposed a partial clinical hold on a handful of trials of magrolimab—raising questions about the program and the billions biopharma has bet on CD47.
The FDA applied the partial clinical hold to studies that are testing magrolimab—the anti-CD47 antibody Gilead acquired in its $4.9 billion takeover of Forty Seven—in combination with azacitidine. The partial clinical hold means the screening and enrollment of new participants in three phase 3 studies and two earlier-phase trials is on hold. One of the earlier-phase trials could support accelerated approval.
Management at Gilead attributed the partial hold to an “apparent imbalance in investigator-reported suspected unexpected serious adverse reactions between study arms.” Gilead is yet to identify a “clear trend in the adverse reactions or new safety signal.” To address the concerns raised by the FDA, Gilead is now gathering and analyzing data with a view to determining the next steps to release the partial clinical hold. Gilead is yet to share a timeline for getting the hold lifted.
“Considering the high unmet need for new medicines in myelodysplastic syndrome and acute myeloid leukemia, we will work closely with regulatory authorities worldwide to continue the magrolimab development program appropriately. We remain confident in the potential of magrolimab across a broad range of tumors,” Merdad Parsey, M.D., Ph.D., chief medical officer at Gilead, said in a statement.
Existing participants will continue to receive the cocktail of magrolimab and azacitidine, also known as Vidaza, and enrollment is continuing in five phase 2 clinical trials that are testing the CD47 drug as a monotherapy and in combination with other molecules. Gilead is also continuing to work on another phase 2 trial, in colorectal cancer, that is at the planning stage.
At best, the partial clinical hold represents a delay that will eat away at the lead Gilead enjoys over other developers of anti-CD47 antibodies, particularly as the paused phase 1b, which offered a possible route to accelerated approval, was due to post data this quarter. Gilead delayed the readout last year and now faces a further delay.
At worst, the regulatory action could be a harbinger of tough times for the broader CD47 market. With little known publicly about the cause of the hold, it is unclear whether the issue is likely to be limited to magrolimab or if it may affect similar molecules in development at Pfizer, which paid $2.3 billion to enter the space, and AbbVie. The broader CD47 sector will be following the situation at Gilead closely as rivals evaluate whether the hold represents an opportunity to close the gap on magrolimab, a potential point of differentiation for their molecules or a possible threat to their own plans.