Magrolimab, a First-in-Class Anti-CD47 Monoclonal Antibody, Shows 63% Overall Response Rate in Frontline AML Treatment

December 08, 2020 /BioValleyBIOON/ -- Gilead Sciences recently announced at the 62nd Annual Meeting of the American Society of Hematology (ASH) the evaluation of magrolimab, a first-in-class anti-CD47 monoclonal antibody, as a first-line treatment for acute myeloidLeukemiaLatest Results from the Phase 1b Clinical Study of (AML). The study was conducted in patients with AML who had not previously received treatment and were ineligible for intensive chemotherapy, including those with TP53-mutated AML.

The results showed that treatment with magrolimab in combination with azacitidine achieved a very high response rate: in the overall study population,The overall response rate (ORR) was 63% (n=27/43), while the ORR in patients with TP53 mutations was 69% (n=20/29).

David Sallman, M.D., an investigator in the study and a physician at the H. Lee Moffitt Cancer Center & Research Institute, stated, “In this ongoing study, the combination of magrolimab and azacitidine continues to demonstrate promising and durable efficacy in patients with acute myeloid leukemia (AML) who are ineligible for first-line chemotherapy. These findings are particularly encouraging for patients with TP53 mutations, which are associated with poor prognosis and limited response to existing treatment regimens.”

In this study, 64 patients received magrolimab in combination with azacitidine, including 47 patients with TP53 mutations, a population that is difficult to treat and has a poor prognosis. As of November 2020, 63% (n=27/43) of efficacy-evaluable patients achieved an objective response according to the European LeukemiaNet 2017 criteria, 42% (n=18/43) achieved complete remission (CR), and 12% (n=5/43) achieved CR with incomplete hematologic recovery (CRi). The median duration of response (DOR) was 9.6 months (range: 0.03+ to 18.7 months), and the median time to response was 1.95 months (range: 0.95 to 5.6 months).

Among patients with TP53 mutations, 69% (n=20/29) achieved response, 45% (n=13/29) achieved complete remission (CR), and 14% (n=4/29) achieved complete remission with incomplete hematologic recovery (CRi). The median duration of response (DOR) was 7.6 months (range: 0.03+ to 15.1+ months). The rate of minimal residual disease (MRD) negativity among patients achieving CR/CRi was 29% (n=5/17).

For patients with wild-type TP53 (n=16), the preliminary median overall survival (OS) was 18.9 months (95% CI: 4.34, NE), whereas for patients with mutated TP53 (n=47), the preliminary median OS was 12.9 months (95% CI: 8.21, 17.28). The median follow-up times for patients with wild-type TP53 and mutated TP53 were 12.5 months and 4.7 months, respectively. Additional patients and longer follow-up are required to further determine the survival benefit.

In the study, common treatment-related adverse events (incidence >15%) observed includedAnemia, fatigue, elevated blood bilirubin, infusion-related reactions, neutropenia, thrombocytopenia, and elevated ALT. Most patients had thrombocytopenia at baseline, and no significant increase in thrombocytopenia, infections, or immune-related adverse events (AEs) was observed during the study. The 30-day all-cause mortality rate was 4.7% (n=3/64), and the 60-day mortality rate was 7.8% (n=5/64). Treatment was discontinued due to drug-related adverse events in 4.7% of patients.

Mechanism of Action of Magrolimab (Click the image to view a larger version)

Magrolimab is a monoclonal antibody that blocks CD47 signaling, acquired by Gilead Sciences in April this year following its approximately $4.9 billion acquisition of Forty Seven.. Magrolimab is designed to interfere with the recognition of CD47 by the SIRPα receptor on macrophages, thereby blocking cancer cells from using the “don’t eat me” signal to avoid phagocytosis by macrophages.

Currently, magrolimab is being evaluated in several hematologic and solid tumor malignanciesTumordevelopment, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Previously, magrolimab was granted Fast Track Designation (FTD) by the FDA for the treatment of MDS, AML, diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). Magrolimab has also beenFDAGranted Orphan Drug Designation (ODD) for the treatment of MDS and AML, and granted Orphan Drug Designation by the European Medicines Agency (EMA) for the treatment of AML.

This September,FDAGranted Breakthrough Therapy Designation (BTD) for magrolimab as a first-line treatment for MDS. MDS is a cancer caused by poorly formed or dysfunctional blood cells in the bone marrow. In the United States, approximately 15,000 people areDiagnosisSince the approval of MDS treatments, no new therapies have been approved in 14 years. The median survival for patients with low-risk MDS is 6 years, while it is approximately 18 months for those with high-risk MDS.

This Breakthrough Therapy Designation (BTD) is based on positive results from an ongoing Phase 1b study evaluating the combination of magrolimab and azacitidine in previously untreated patients with intermediate-, high-, and very-high-risk myelodysplastic syndromes (MDS). Data presented at the 2020 European Hematology Association (EHA) Congress showed that among evaluable patients (n=33) treated with magrolimab plus azacitidine, the objective response rate (ORR) was as high as 91%, and the complete response (CR) rate reached 42%. The combination of magrolimab and azacitidine was well tolerated. The maximum tolerated dose was not reached, and no MDS patients discontinued treatment due to treatment-related adverse events.

Currently, magrolimab is undergoing the double-blind, placebo-controlled, randomized Phase 3 ENHANCE trial for previously untreated high-risk MDS patients. The trial will evaluate the safety and efficacy of magrolimab in combination with azacitidine by assessing CR and duration of CR. (Bioon.com)

Original Source: Magrolimab Demonstrates Clinical Responses in Ongoing Phase 1b Trial of Previously Untreated Acute Myeloid Leukemia Patients