MAGROLIMAB DEMONSTRATES CLINICAL RESPONSES IN ONGOING PHASE 1B TRIAL OF PREVIOUSLY UNTREATED ACUTE MYELOID LEUKAEMIA PATIENTS

-- Similar Overall and Complete Response Rates Observed Across Frontline AML Patients Ineligible for Intensive Chemotherapy and in High Unmet Need Patients with TP53-Mutant AML -- 

Stockley Park, UK – 6 December 2020 – Gilead Sciences, Inc. today announced updated results from the magrolimab Phase 1b trial. Magrolimab is an investigational, first-in-class, anti-CD47 monoclonal antibody being studied in previously untreated acute myeloid leukaemia (AML) patients who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML. The study continues to demonstrate high response rates with magrolimab in combination with azacitidine, with an overall response rate of 63% (n=27/43) among the total patient population and 69% (n=20/29) in TP53-mutant patients. The data were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract #330).¹

“In this ongoing study, treatment with magrolimab and azacitidine continues to achieve promising, durable responses in patients with AML who are ineligible for first-line chemotherapy,” said David Sallman, MD, H. Lee Moffitt Cancer Center and Research Institute, an investigator for the clinical trial. “These findings are especially encouraging for patients with TP53 mutations, which is associated with poor outcomes and limited response to existing treatment options.”  

In the study, 64 patients were treated with magrolimab plus azacitidine, including 47 patients with the TP53 mutation, a treatment-refractory and poor-prognosis population. As of November 2020, 63% (n=27/43) of patients evaluable for efficacy achieved an objective response per European LeukemiaNet 2017 criteria, 42% (n=18/43) achieved a complete remission (CR), and 12% (n=5/43) achieved a CR with an incomplete count 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).  

For patients with the TP53 mutation, 69% (n=20/29) achieved a response, 45% (n=13/29) achieved a CR and 14% (n=4/29) achieved a CRi. The median DOR was 7.6 months (range: 0.03+ to 15.1+ months) and the minimum residual disease (MRD) negativity in patients with a CR/CRi was 29% (n=5/17).  

Preliminary median overall survival (OS) for TP53-wild-type patients (n=16) was 18.9 months (95% CI: 4.34, NE) and for TP53-mutant patients (n=47) was 12.9 months (95% CI: 8.21, 17.28). The median follow-up for TP53-wild-type and TP53-mutant patients was 12.5 months and 4.7 months, respectively. Additional patients and longer follow-up in a comparative trial are needed to further characterise the survival benefit. 

Treatment-related adverse events observed over 15% incidence included anaemia, fatigue, blood bilirubin increase, infusion related reaction, neutropenia, thrombocytopenia and ALT increase. Most patients were cytopenic at baseline, and no significant increased cytopenias, infections or immune-related adverse events (AEs) were observed in the study. Thirty-day all-cause mortality was 4.7% (n=3/64), and 60-day mortality was 7.8% (n=5/64). Treatment discontinuation due to drug-related AE occurred in 4.7% of all patients. 

“We continue to be encouraged by the response rates seen in this study and are rapidly advancing the development of magrolimab based on its potential to help address significant unmet medical needs,” said Daejin Abidoye, Senior Vice President, Head of Oncology, Gilead Sciences. “In early 2021, we will be initiating a Phase 3 trial of magrolimab and azacitidine in previously untreated patients with TP53-mutant AML who are ineligible for intensive chemotherapy and continue to study additional magrolimab treatment combinations broadly across AML populations, including mutational subtypes.”   

Magrolimab is investigational and not approved anywhere globally. Its efficacy and safety have not been established. 

About Acute Myeloid Leukaemia (AML) 

AML is a type of cancer that starts in the bone marrow and can quickly move to the blood and other parts of the body, including the lymph nodes, spleen and central nervous system. AML most often develops from cells that would turn into red blood cells, neutrophils, and platelets but can also evolve from other blood disorders such as myelodysplastic syndromes.²

About the Study 

The Phase 1b trial, funded in part by the California Institute of Regenerative Medicine (CIRM), is designed to evaluate the safety, tolerability and efficacy of magrolimab combined with azacitidine in untreated patients with AML who are ineligible for induction chemotherapy. All patients in the trial received a magrolimab 1 mg/kg priming dose, coupled with intrapatient dose escalation, to mitigate on-target anaemia. Patients were then treated with full doses of azacitidine and a magrolimab maintenance dose of 30 mg/kg once weekly or every two weeks. Based on pharmacokinetics and CD47 receptor occupancy data in the bone marrow from the ongoing trial, dosing every two weeks has been selected to optimize patient convenience. 

About Magrolimab 

Magrolimab is a potential, first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don't eat me" signal used by cancer cells to avoid being ingested by macrophages. Magrolimab is being developed in several hematologic cancers, including myelodysplastic syndrome (MDS), as well as solid tumour malignancies. 

Magrolimab received PRIME Designation for treatment of MDS from the European Medicines Agency (EMA). In addition, magrolimab received Fast Track Designation by the FDA for the treatment of MDS, AML, diffuse large B cell lymphoma (DLBCL) and follicular lymphoma; and has been granted Orphan Drug Designation by the FDA and EMA for MDS and AML. The U.S. Food and Drug Administration (FDA) recently assigned Breakthrough Designation to magrolimab, in combination with azacitidine, for the treatment of adult patients with newly-diagnosed MDS including intermediate-, high-, or very high-risk tumour types. 

About Gilead Sciences 

Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercialises innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.  

Gilead Forward-Looking Statement 

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from ongoing and additional clinical studies involving magrolimab, including in combination with azacitidine, and the possibility that Gilead may be unable to initiate and complete future studies involving magrolimab in the anticipated timelines or at all. Further, it is possible that Gilead may make a strategic decision to discontinue development of magrolimab. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation to update any such forward-looking statements. 

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¹ Sallman, et al. The First-in-Class Anti-CD47 Antibody Magrolimab Combined with Azacitidine Is Well-Tolerated and Effective in AML Patients: Phase 1b Results. Abstract #330 (Oral) presented 6 December 2020 (17:30 GMT/18:30 CET) at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

² American Cancer Society. What Is Acute Myeloid Leukemia (AML)? Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html. Accessed December 2020.

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