Gilead Sciences’ abandoned anti-CD47 drug magrolimab was not just ineffective, but could potentially be harmful to patients with untreated high-risk myelodysplastic syndrome, according to new data from a phase 3 study presented at 2024’s European Hematology Association (EHA) meeting.
Magrolimab showed worse performances compared with placebo across multiple efficacy and safety metrics in their respective combinations with chemotherapy, data from the ENHANCE trial have shown.
The magrolimab-chemo regimen was tied to a 20.3% increased risk of death, though the results were not statistically significant, with a p-value of 0.13. Patients who got the investigational therapy lived a median 15.9 months, versus 18.6 months for those in the control arm.
On the trial’s other primary endpoint, the complete remission rate (CRR) was numerically lower at 21.3% for patients receiving magrolimab, versus 23.6% for the placebo group.
Gilead had already slammed the brakes on the ENHANCE study after a prespecified interim analysis indicated that it likely wouldn’t succeed. Now detailed data show that not only did the trial miss its primary endpoints measuring overall survival and CRR, but, also, patients receiving the Gilead med were two times as likely to discontinue treatment due to adverse events compared to placebo. The rates were 24% and 12.1%, respectively.
Overall, grade 3 or above adverse events deemed related to a study drug happened in 76.4% of 263 patients in the magrolimab arm versus 56.4% of 264 patients for the control group.
The findings highlight challenges of developing anti-CD47 therapies and other new treatments in the indication, the abstract authors wrote.
Gilead abandoned the monoclonal antibody entirely at the end of April after ending development in blood cancers in February. The company had previously also paused enrollment on solid tumor trials in February when the FDA asked for a partial clinical hold on the studies after the antibody failed phase 3 trials and was linked to patient deaths.
Magrolimab was the centerpiece of Gilead’s $4.9 billion acquisition of Forty Seven back in 2020. At the time, Gilead wanted to expand its cancer portfolio further, and analysts saw the antibody as a potential “pipeline in a product” that could unlock opportunities across a wide range of blood cancers and solid tumors.
“The discontinuation of magrolimab studies is the result of a critical review of all available safety and efficacy data in both solid tumors and hematologic malignancies,” a Gilead spokesperson told Fierce Biotech.
Now, it appears the company is spending some resources on the hot market of obesity, investing across early-stage obesity and metabolic programs.
Gilead plans to share new preclinical data for an oral GLP-1 at the upcoming American Diabetes Association conference starting June 21, according to a Jefferies note posted June 13. The asset, dubbed GS-4571, has previously demonstrated 5% to 8% weight loss in monkeys in 28 to 30 days—which is in the range of other GLP-1s—and boosted glucose tolerance while decreasing food intake, according to the analyst.
While Gilead currently doesn’t have any obesity assets in its clinical pipeline, the company does have a stake in a private DNP mitochondria uncoupling company that touts a phase 1 oral obesity drug, according to Jeffries. Twelve-week data for the drug, which originally came from Gilead and was spun out into the new company, are anticipated in the second half of this year.
The company is also currently running a phase 2 clinical trial evaluating potential combinations with Novo Nordisk’s GLP-1 agonist semaglutide for patients with metabolic dysfunction-associated steatohepatitis. The study has a primary completion date slated for November of this year, according to ClinicalTrials.gov.