FDA Places Second Partial Clinical Hold on AML Enrollment for Magrolimab Trials

The FDA has placed another partial clinical hold on the enrollment of new patients in United States clinical trials evaluating the potential first-in-class investigational anti-CD47 immunotherapy magrolimab for the treatment of acute myeloid leukemia (AML), according to an announcement from Gilead Sciences.¹

The FDA’s decision follows the previously announced discontinuation of the phase 3 ENHANCE trial (NCT04313881), which had been evaluating magrolimab in patients with higher-risk myelodysplastic syndromes (HR-MDS).

Effective immediately, screening and enrollment of new patients under the US investigational new drug application (IND 147229) and US Expanded Access Program will be paused. However, patients who have already been enrolled in AML clinical trials evaluating magrolimab will be allowed to continue to receive treatment and follow-up, according to the current study protocol.

Such trials affected by the decision include the phase 3 ENHANCE-2 trial (NCT04778397), which is evaluating the combination of magrolimab and azacitidine vs venetoclax (Venclexta) plus azacitidine or intensive chemotherapy in treatment-naïve patients with TP53-mutant AML, and the phase 3 ENHANCE-3 trial (NCT05079230), which is evaluating magrolimab plus venetoclax and azacitidine vs placebo plus venetoclax and azacitidine in treatment-naïve patients with AML unfit for chemotherapy.²

In January 2022, the FDA placed a partial clinical hold on all trials evaluating magrolimab plus azacytidine.³ In April 2022, the FDA lifted the clinical hold for all trials evaluating the combination in patients with MDS and AML following a thorough review of the safety data.

News of the FDA’s decision has been relayed to global regulatory agencies and clinical trial investigators involved in the studies. Studies of magrolimab in solid tumors including head and neck cancer, colorectal cancer, lung cancer, and breast cancer, will be unaffected by the FDA’s decision.¹

Gilead is working with the regulatory agencies to identify next steps to release the partial clinical hold for new patient enrollment in studies of magrolimab in AML.

References

1. Gilead announces partial clinical hold for magrolimab studies in AML. News release. Gilead Sciences, Inc. August 21, 2023. Accessed August 21, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/8/gilead-announces-partial-clinical-hold-for-magrolimab-studies-in-aml
2. Gilead to discontinue phase 3 ENHANCE study of magrolimab plus azacitidine in higher-risk MDS. News release. Gilead Sciences, Inc. July 21, 2023. Accessed August 21, 2023. 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
3. Gilead ends late-stage trial for magrolumab in blood cancer treatment. News release. BioSpace. July 24, 2023. Accessed August 21, 2023. https://www.biospace.com/article/gilead-drops-late-stage-trial-for-magrolimab-in-blood-cancer-treatment/