FDA Places Partial Clinical Hold on Magrolimab Trials in AML

The FDA’s clinical hold follows the discontinuation of the phase 3 ENHANCE study (NCT04313881) evaluating magrolimab in combination with azacitidine as a treatment for patients with higher-risk myelodysplastic syndrome.

The FDA has placed a partial clinical hold on the enrollment of patients on clinical trials evaluating magrolimab as a treatment for acute myeloid leukemia (AML), according to a press release from Gilead Sciences, Inc.¹

Under the clinical hold, investigators must pause screening and enrollment of new patients as part of the investigational new drug application and expanded access program for magrolimab. Patients with AML who are already receiving magrolimab as part of a clinical trial are eligible to continue treatment in accordance with study protocol.

The clinical hold does not impact any studies assessing magrolimab as a treatment for patients with solid tumors. Developers are collaborating with regulatory authorities to discuss the appropriate next steps for lifting the partial clinical hold on AML studies.

Magrolimab is an investigational anti-CD47 immunotherapy designed to block the CD47-signal regulatory protein interaction, thereby enabling macrophages and other phagocytes to identify and destroy malignant cells. Developers designed the agent as a potential treatment for AML and other cancer types including lymphoma, multiple myeloma, head and neck cancer, colorectal cancer, and breast cancer.

The FDA’s clinical hold follows the discontinuation of the phase 3 ENHANCE study (NCT04313881) evaluating magrolimab in combination with azacitidine as a treatment for patients with higher-risk myelodysplastic syndrome (MDS).² Investigators decided to discontinue their assessment of magrolimab after reporting futility in a planned analysis.

“The health and well-being of patients are our top priorities and while this is disappointing news, it confirms the challenges of treating [higher-risk] MDS, where no new class of treatments have been approved in nearly 20 years,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in a press release at the time investigators terminated the ENHANCE study.²

The FDA previously placed a clinical hold on magrolimab/azacitidine trials in AML and MDS in January 2022.³ The regulatory agency instituted an international clinical hold due to an imbalance of unexpected investigator-reported adverse effects (AEs) across treatment arms. The FDA lifted the clinical hold on the magrolimab/azacitidine trials in April 2022 after the results of a comprehensive safety data review allowed investigators to continue their assessment of the regimen.⁴

The FDA granted breakthrough therapy designation to magrolimab in newly diagnosed MDS in September 2020.⁵ Supporting data for this designation came from a phase 1b study in which investigators reported an objective response rate of 91% in a population of 33 evaluable patients treated with magrolimab. Additionally, 42% of patients achieved a complete remission. Investigators indicated that no patients discontinued treatment following a treatment-related AE.

References

1. Gilead announces partial clinical hold for magrolimab studies in AML. News release. Gilead Sciences, Inc. August 21, 2023. Accessed August 22, 2023. https://shorturl.at/jBDI4
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 22, 2023. bit.ly/3Qd0xzk
3. Gilead announces partial clinical hold for studies evaluating magrolimab in combination with azacitidine. News release. Gilead Sciences, Inc. January 25, 2022. Accessed August 22, 2023. bit.ly/3Ycu3ar
4. FDA lifts partial clinical hold on MDS and AML magrolimab studies. News release. Gilead Sciences, Inc. April 11, 2022. Accessed July 24. 2023. bit.ly/44BYM3f
5. 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 August 22, 2023. bit.ly/43C2EQs