FDA Places Hold on Clinical Trials of Magrolimab for Blood Cancers

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Gilead Sciences, Inc. will discontinue the clinical development of magrolimab for hematologic cancers after it was found to increase the risk of death in combination with azacitidine (Vidaza, Onureg) plus Venclexta (venetoclax) in a Phase III trial.¹ As a result, the FDA placed all magrolimab studies in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) on full clinical hold.

The ENHANCE-3 trial (NCT05079230) was evaluating the magrolimab combination in patients with AML. Top-line data from a planned interim analysis conducted by an independent Data Monitoring Committee showed futility with the magrolimab plus azacitidine and Venclexta combination, as well as an increased risk of death related to infections and respiratory failure.

In addition to the ENHANCE-3 trial, magrolimab was also being evaluated in the ENHANCE trial among patients with higher-risk MDS and in the ENHANCE-2 trial among patients with AML with TP53 mutations. Gilead said that the primary analyses for these trials also showed futility with an increased risk of death in patients.

“The complexity of treating blood cancer is highlighted in these results,” said Gilead Sciences Chief Medical Officer Merdad Parsey, MD, PhD, in a press release. “We are incredibly grateful to all the patients and investigators for their participation in the ENHANCE studies.”¹

Gilead said it will discuss appropriate next steps with investigators for patients enrolled in the ENHANCE-3 trial. Sub-analyses for efficacy and safety from the trial are ongoing and data will be shared with regulatory authorities and presented at an upcoming medical meeting and/or published in a peer-reviewed journal, Gilead stated in the release.

Other clinical trials of magrolimab include in combination with bevacizumab and 5-fluorouracil, irinotecan, and leucovorin in previously treated patients with advanced inoperable metastatic colorectal cancer; with other anticancer therapies in patients with head and neck squamous cell carcinoma; in combination with multiple immunotherapies in patients with locally advanced or metastatic urothelial carcinoma who progressed during or following a platinum-containing regimen; in combination with olaparib for the treatment of patients with breast or castrate-resistant prostate cancer; and in combination with nab-paclitaxel or paclitaxel, or sacituzumab govitecan-hziy in patients with locally advanced or metastatic triple-negative breast cancer.²

A potential first-in-class, humanized monoclonal antibody, magrolimab was granted FDA Breakthrough Therapy Designation in combination with azacitidine for treatment-naïve patients with high- and very high-risk MDS in September 2020.³

Magrolimab was developed to inhibit the recognition of CD47 by the SIRPα receptor on macrophages, which enabled the drug to block the signal cancer cells use to evade ingestion by these macrophages.

Gilead previously announced it was discontinuing the Phase III ENHANCE study of magrolimab plus azacitidine in the first-line treatment of higher-risk MDS after a planned analysis showed futility with the combination.⁴

“The health and well-being 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,” Parsey said in a July 2023 press release.⁴

Gilead announced that it will share top-line results from all pivotal magrolimab trials and is reviewing safety data for magrolimab across all ongoing solid tumor trials, which it will share “as soon as possible.”

References

1. Gilead Statement on Discontinuation of Phase 3 ENHANCE-3 Study in AML. Gilead. News release. February 7, 2024. Accessed February 7, 2024. https://www.gilead.com/news-and-press/company-statements/gilead-statement-on-discontinuation-of-phase-3-enhance-3-study-in-aml

2. National Cancer Institute. Clinical Trials Using Magrolimab. Webpage. Accessed February 7, 2024. https://www.cancer.gov/research/participate/clinical-trials/intervention/magrolimab

3. Gilead’s magrolimab, an investigational anti-CD47 monoclonal antibody, receives FDA breakthrough therapy designation for treatment of myelodysplastic syndrome. News release. Gilead Sciences, Inc. September 15, 2020. Accessed February 7, 2024. https://investors.gilead.com/news-releases/news-release-details/gileads-magrolimab-investigational-anti-cd47-monoclonal-antibody/

4. Gilead To Discontinue Phase 3 ENHANCE Study of Magrolimab Plus Azacitidine in Higher-Risk MDS. Gilead. News release. July 21, 2023. Accessed February 7, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2023/7/gilead-to-discontinue-phase-3-enhance-study-of-magrolimab-plus-azacitidine-in-higher-risk-mds