Discovered and developed by GlycoMimetics, uproleselan (yoo’ pro le’se lan) is an investigational, first-in-class, E-selectin antagonist. GlycoMimetics has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration (FDA) and Breakthrough Therapy designation from the Chinese National Medical Products Administration for uproleselan as a potential treatment for adult Acute Myeloid Leukemia (AML) patients with relapsed or refractory (R/R) disease.
On May 6, 2024, GlycoMimetics announced results of its pivotal Phase 3 study of uproleselan in R/R AML [press release]. Uproleselan is also being evaluated in a Phase 2/3 adaptive study sponsored by the National Cancer Institute (NCI) as a potential new treatment for newly diagnosed AML patients who are 60 years or older and fit for intensive chemotherapy. The Alliance for Clinical Trials in Oncology is conducting the randomized, Phase 2 controlled study evaluating the addition of uproleselan to a standard cytarabine/daunorubicin regimen (7+3) versus chemotherapy alone. The Phase 2 portion of the study completed enrollment of 267 patients in December 2021. Results of the pre-planned Phase 2 event free survival interim analysis will be reported when available.
E-selectin is a leukocyte adhesion molecule constitutively expressed on endothelial cells of the vasculature and bone marrow. In AML, there is evidence that E-selectin–ligand interaction between endothelial cells in the protective niche of the Bone Marrow microEnvironment (BME) and leukemic stem cells and blasts promotes leukemic cell survival and hides them from AML therapies. Uproleselan is designed to disrupt E-selectin binding and prevent leukemic myeloid cells using the protective niche of the BME.
Results of a Phase 1/2 trial of adults living with relapsed/refractory AML treated with uproleselan were published on September 16, 2021, in BLOOD. Findings included:
- A high remission rate compared to historical experience with salvage chemotherapy alone. In the relapsed/refractory (R/R) population, 41% achieved a Complete Response (CR)/Complete response incomplete hematologic recovery (Cri), and, of note, 35% achieved CRs, which highlights the recovery of bone marrow in addition to anti-leukemic effect;
- A majority of evaluable patients achieved measurable residual disease (MRD) negativity at the end of induction, including a 69% (11/16) negative rate in the evaluable R/R AML population and a 56% (5/9) rate MRD negative rate in the evaluable de novo AML population; full CR with MRD negative status has been shown to be the strongest predictor for overall survival in AML;
- A high percentage of responding patients undergoing a subsequent transplant – 31% of patients (17/54) in the R/R patients went on to allogeneic stem cell transplantation. This suggests that the addition of uproleselan to chemotherapy was associated not only with anti-leukemic effect but also with preserved performance status that allowed patients to undergo stem cell transplant while in remission, both critical factors for the success of transplantation;
- The addition of uproleselan to chemotherapy was well tolerated, with high remission rates, low induction mortality, and low rates of mucositis, providing a strong rationale for phase 3 randomized confirmatory studies.
Regulatory Designations*
Breakthrough Therapy – U.S. FDA and Chinese Health Authority in adult relapsed/refractory AML
Fast Track – U.S. FDA in adult relapsed/refractory AML
Orphan Drug – U.S. FDA and European Union
*Uproleselan has not been approved for use by any worldwide health authority