Uproleselan Plus Chemotherapy Misses OS End Point in R/R AML


Uproleselan plus chemotherapy did not achieve a statistically significant improvement in OS vs chemotherapy alone in patients with relapsed/refractory AML.

Harout Semerjian, CEO of GlycoMimetics

Harout Semerjian, CEO of GlycoMimetics

The combination of uproleselan (GMI-1271) and chemotherapy did not achieve a statistically significant improvement in overall survival (OS) vs chemotherapy alone in patients with relapsed/refractory acute myeloid leukemia (AML), according to topline results from a phase 3 global study (NCT03616470).1

In the study, 388 patients were treated with uproleselan and had a median OS of 13 months compared with a median OS of 12.3 months in the placebo arm, missing the primary end point.

“While the outcome of our Phase 3 study in relapsed/refractory AML is not what we hoped, we wish to thank the investigators, the participating patients and their families for their dedication to this large, well-controlled randomized study,” Harout Semerjian, chief executive officer of GlycoMimetics, stated in a news release. “We are thoroughly analyzing the data in collaboration with medical, statistical and regulatory experts and are committed to submitting a comprehensive data analysis for presentation at an upcoming medical meeting.”

AML, the most common acute leukemia in adults, originates in the bone marrow and affects approximately 21,000 individuals in the United States annually. Despite the availability of various treatments, disease prognosis remains poor, creating an unmet need and necessitating the development of additional therapeutic options to enhance outcomes in patients. Uproleselan has received breakthrough therapy and fast track designations from the FDA, as well as a breakthrough therapy designation from the Chinese National Medical Products Administration, for the treatment of adult patients with relapsed/refractory AML.

Uproleselan targets E-selectin, a leukocyte adhesion molecule expressed on endothelial cells within the vasculature and bone marrow. In AML, the interaction between E-selectin and its ligands within the protective niche of the bone marrow microenvironment contributes to leukemic cell survival and resistance to conventional therapies. Uproleselan is designed to disrupt this interaction, thereby preventing leukemic myeloid cells from using the protective microenvironment for survival.

The randomized, double-blind, placebo-controlled phase 3 trial evaluated uproleselan in combination with MEC (mitoxantrone, etoposide, and cytarabine) or FAI (fludarabine, cytarabine, and idarubicin) in patients with relapsed/refractory AML. Patients between 18 and 75 years of age with relapsed/refractory AML who had undergone no more than 1 prior stem cell transplant were eligible for inclusion in the study.2 Patients could not have received prior treatment with the study chemotherapy regimen. Additional exclusion criteria included patients with specific types of leukemia, active central nervous system involvement, or a recent stem cell transplantation within 4 months prior to dosing. Patients also could not have received immunotherapy, radiotherapy, experimental therapy, or chemotherapy within specified timeframes prior to dosing, and should not have used certain medications such as granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or plerixafor before dosing. Patients were randomly assigned 1:1 between treatment and placebo arms across 70 sites in 9 countries.1

On the trial, eligible patients received either uproleselan or placebo for 8 days over 1 cycle of induction and, if applicable, up to 3 cycles of consolidation. The primary end point of the study was OS without censoring for transplant; secondary end points included incidence of severe oral mucositis, complete remission rate, and remission rate.

Regarding safety, adverse events (AEs) were consistent with known AE profiles of the chemotherapy regimens used in the study.

Looking to the future, the National Cancer Institute and the Alliance for Clinical Trials in Oncology are currently conducting an adaptive phase 2/3 trial (NCT03701308) investigating uproleselan in adult patients ages 60 years and older with newly diagnosed AML who are suitable for intensive chemotherapy. This randomized, controlled study will assess the impact of adding uproleselan to a standard cytarabine/daunorubicin regimen compared with chemotherapy alone. Enrollment for the phase 2 portion of the trial completed enrollment of 267 eligible patients in December 2021, and the results from the preplanned phase 2 interim analysis on event-free survival will be reported as they become available.


  1. GlycoMimetics announces results of pivotal phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). News Release. GlycoMimetics, Inc. May 6, 2024. Accessed May 6, 2024.
  2. Study to determine the efficacy of uproleselan (GMI-1271) in combination with chemotherapy to treat relapsed/refractory acute myeloid leukemia. Updated July 25, 2023. Accessed May 6, 2024.

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