Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1085 |
| INN | Magrolimab |
| Status | Terminated |
| Drug code(s) | IPH2102, BMS-986015, ONO-4483, 1-7F9 |
| Brand name | None |
| mAb sequence source | mAb humanized |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG4 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | CD47 |
| Indications of clinical studies | Triple-Negative Breast Cancer, Head & neck cancer, acute Myeloid Leukemia, Myeloid Malignancies, r/r DLBCL, ovarian cancer, colorectal cancer, non-Hodgkin's lymphoma, solid tumors, leukemia |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Terminated at Phase 3 |
| Status | Inactive |
| Start of clinical phase (IND filing or first Phase 1) | August 15, 2014 |
| Start of Phase 2 | November 15, 2016 |
| Start of Phase 3 | September 09, 2020 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Gilead Sciences, Inc. |
| Licensee/Partner | Ono Pharmaceutical Co |
| Comments about company or candidate | Phase 3 ENHANCE study was discontinued due to futility at a prespecified interim analysis Removed from Gilead pipeline in Q1 2024 (https://s29.q4cdn.com/585078350/files/doc_financials/2024/q1/GILD-Q124-Earnings-Presentation-25-April-2024.pdf) February 7, 2024 – Gilead Sciences, Inc. announced it has discontinued the Phase 3 ENHANCE-3 study of magrolimab in acute myeloid leukemia (AML) and that the U.S. Food and Drug Administration (FDA) placed all magrolimab studies in myelodysplastic syndromes (MDS) and AML, including related expanded access programs, on full clinical hold. These decisions follow the recommendation of an independent Data Monitoring Committee which reviewed top-line data from a planned interim analysis of ENHANCE-3 for overall survival (OS). In that analysis, magrolimab in combination with azacitidine plus venetoclax demonstrated futility and an increased risk of death was observed, primarily driven by infections and respiratory failure. Based on these results, as well as data from two other clinical studies in higher-risk MDS (ENHANCE) and AML with TP53 mutations (ENHANCE-2) where the primary analyses also demonstrated futility with an increased risk of death in the magrolimab-treatment arm, Gilead will not pursue further development of magrolimab in hematologic cancers. Listed as Phase 3 asset in AML in Ono pipeline dated Jan 24, 2024. July 21, 2023: Gilead Sciences, Inc. announced that the Phase 3 ENHANCE study in higher-risk myelodysplastic syndromes (MDS) has been discontinued due to futility based on a planned analysis. Phase 3 studies for: Myelodisplastic syndromes (NCT04313881) is active not recruiting as of December 2022; Acute myeloid leukemia (NCT04778397, NCT05079230) are recruiting as of May-June 2023 Jan 2023: Listed as Phase 3 asset in Ono pipeline Aug 2022 corporate update: ENHANCE enrollment trending well, expect interim analysis no later than early 2023 Potential BLA submission for Accelerated Approval in MDS in H2 2021; https://investors.gilead.com/static-files/9fc6ee8f-b63c-451b-a8a8-9136bdcfc54c September 15, 2020: Gilead Sciences, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for magrolimab, a first-in-class, investigational anti-CD47 monoclonal antibody for the treatment of newly diagnosed myelodysplastic syndrome (MDS). NCT04313881 Phase 3 ENHANCE study in MDS is not yet recruiting as of Sep 21 2020. A potential registration single arm MDS cohort is ongoing (NCT03248479, A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies). https://www.gilead.com/news-and-press/press-room/press-releases/2020/5/investigational-magrolimab-in-combination-with-azacitidine-demonstrates-durable-activity-in-previously-untreated-myelodysplastic-syndrome-and-acute-my Data were presented during an oral session at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting held from May 29-31 (Abstract #7507). NCT04403308 is a Phase 1 study in solid tumors. March 2, 2020: Gilead Sciences Inc said it would buy Forty Seven Inc for $4.9 billion in cash. Magrolimab has Fast Track designation in four hematologic malignancies: MDS, AML, r/r DLBCL and follicular lymphoma. Sep 2019: The FDA granted fast-track status to Forty Seven's lead candidate, magrolimab, previously known as 5F9, as a treatment for acute myeloid leukemia and myelodysplastic syndromes. Based on feedback from a Type C meeting with the FDA in May 2019, Forty Seven believes that data from a single arm pivotal study evaluating ORR and durability may be sufficient to support the registration of 5F9 in combination with rituximab in patients with r/r DLBCL who have failed at least two prior lines of therapy, including those who have been deemed CAR-T ineligible. The Company is currently finalizing the operational components of the proposed registrational study, including details on trial design and chemistry, manufacturing and controls (CMC), and will provide a detailed update in the second half of 2019. July 11, 2019, Forty Seven, Inc. and Ono Pharmaceutical Co., Ltd. today announced an exclusive license agreement for the development, manufacture and commercialization of 5F9, Forty Seven’s monoclonal antibody against CD47. The agreement includes all therapeutic uses of 5F9 as a monotherapy or combination agent in Japan, South Korea, Taiwan and the ASEAN countries (the “Territory”). Forty Seven will retain all rights to 5F9 in the rest of the world including the United States, Europe and China. NCT03922477 of atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Hu5F9-G4 in AML sponsored by Roche not yet recruiting as of April 22, 2019. NCT03558139 Phase 1 study in ovarian cancer started in May 2018. May 3, 2018 – Forty Seven, Inc., a clinical-stage company focused on developing checkpoint therapies to activate macrophages in the fight against cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted two Fast Track designations to its lead candidate, 5F9, for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), two forms of B-cell non-Hodgkin lymphoma (NHL). 5F9 is a monoclonal antibody against CD47 that is designed to block the “don’t eat me” signal used by cancer cells to avoid being ingested by macrophages. Data justifying these Fast Track designations were derived from an open-label, multi-center Phase 1b/2 clinical trial of 5F9 in combination with rituximab in patients with relapsed or refractory B-cell NHL, including DLBCL and FL. Forty Seven expects to announce initial safety and efficacy data from the Phase 1b portion of the trial in the second quarter of 2018. Two Phase 1/2 studies started in Nov 2016 Forty Seven is a start-up based in CA; founder is Irv Weissman. Antibody was licensed from Stanford; two Phase 1 studies recruiting as of Feb 2016 run by Stanford University. |
| Full address of company | Foster City, California, United States North America United States of America https://www.gilead.com/utility/contact |
Immune checkpoint target. Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and don’t eat me signal on cancers. It induces tumor phagocytosis and eliminates leukemia stem cells. Azacitidine (AZA) synergizes with magrolimab by inducing eat me signals on leukemic cells, enhancing phagocytosis. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.7507
| Anticipated events | None |
| Factor(s) contributing to discontinuation | Lack of efficacy |