In March 2017, LLS began its partnership with Forty Seven to support "A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Rituximab or Rituximab + Chemotherapy in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma" and in July 2019, LLS expanded its partnership by making an equity investment to support "ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome."
LLS funded Stanford University researchers and founders of Forty Seven, Irv Weissman, MD, and Ravi Majeti, MD, PhD, to study seminal work in macrophages. This is a type of immune cell that patrols the body and chews up damaged cells. If a macrophage latches onto a normal cell, a protein known as CD47 sends a “don’t eat me” signal. But lymphoma and leukemia cells are clever and use CD47 to trick the macrophages into ignoring them and letting them grow as cancer. In preclinical mice models, Drs. Weissman and Majeti used an antibody to block the “don’t eat me” signal and stimulate the immune system to recognize the cancer cells as invaders. When they added rituximab as an “eat me” signal, the therapy delivered a one-two punch.
Forty Seven was a clinical-stage immuno-oncology company that was developing therapies targeting cancer immune evasion pathways and specific cell targeting approaches based on technology licensed from Stanford University. Forty Seven’s lead program was magrolimab, a monoclonal antibody against the CD47 receptor, a “don’t eat me” signal that cancer cells commandeer to avoid being ingested by macrophages. Gilead Sciences acquired Forty Seven in April 2020 and continues to develop magrolimab spanning ten potential indications including ongoing trials in solid tumors and two pivotal trials: ENHANCE-2 study in AML with TP53 mutations and ENHANCE-3 in first-line, unfit AML.
Magrolimab has been granted the Fast Track designation by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). It has also been given the Orphan Drug designation by the FDA and the European Medicines Agency for the treatment of AML. More recently in September 2020, the FDA granted Breakthrough Therapy Designation for the treatment of newly diagnosed myelodysplastic syndrome.
Gilead is continuing to explore the role of magrolimab in the following Phase 3 registration-enabling clinical trials:
- Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome (ENHANCE) (NCT04313881) - enrollment completed, announced on July 21, 2023 that trial would be discontinued
- Study to Evaluate the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Adults With TP53 Mutant Acute Myeloid Leukemia (ENHANCE-2) (NCT04778397) - actively enrolling
- Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia (ENHANCE-3) (NCT05079230) - actively enrolling
For more information about Gilead, visit www.gilead.com.
- July 21, 2023 - announced that the Phase 3 ENHANCE study in higher-risk MDS has been discontinued due to futility based on a planned analysis. The magrolimab clinical development program continues spanning ten potential indications including ongoing trials in solid tumors and two pivotal trials: ENHANCE-2 study in AML with TP53 mutations and ENHANCE-3 in first-line, unfit AML.
- May 17, 2022 - announced that 3 abstracts for magrolimab, an investigational anti-CD47 antibody will be presented at the 2022 ASCO Annual Meeting. These data highlight promising data in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
- November 4, 2021 - announced that data at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition (December 11-14) will showcase early-stage research on magrolimab, an investigational CD47 inhibitor, both in an oral session and in an ASH-EHA Joint Symposium. In addition, four trials in progress will be on display highlighting ongoing clinical trials of magrolimab in myeloma, AML and MDS.
- December 06, 2020 - announced updated results from the magrolimab Phase 1b trial. Magrolimab is an investigational, potential first-in-class, anti-CD47 monoclonal antibody being studied in previously untreated acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML. The data were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
- September 15, 2020 - 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).
- May 29, 2020 - announced updated results from a single-arm, open-label Phase 1b trial of magrolimab, an investigational anti-CD47 monoclonal antibody, in combination with azacitidine in previously untreated patients with higher-risk myelodysplastic syndrome (MDS) and previously untreated patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML, a high unmet need population. Results continue to support the clinical activity of magrolimab and azacitidine. The data were presented during an oral session at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting