RARE Daily

GlycoMimetics’ Uproleselan Fails Pivotal Phase 3 Study in Relapsed/Refractory AML

May 6, 2024

Rare Daily Staff

GlycoMimetics said the phase 3 global pivotal study of its experimental treatment for relapsed/refractory acute myeloid leukemia, combined with chemotherapy, did not meet the primary endpoint of improved overall survival versus chemotherapy alone.

Patients treated with uproleselan had a median overall survival of 13 months, compared to 12.3 months in the placebo arm. Adverse events were consistent with known side effect profiles of chemotherapy used in the study.

“While the outcome of our phase 3 study in R/R AML is not what we hoped, 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.” said Harout Semerjian, CEO of GlycoMimetics.

AML is the most common acute leukemia in adults. A cancer of the bone marrow, nearly 21,000 people in the United States are diagnosed with AML each year. Despite the availability of multiple treatments, disease prognosis is poor, and new treatment options are needed to improve outcomes. Newly diagnosed AML has the lowest 5-year survival rate of all leukemias at 31.7 percent. The five-year survival rate for people with relapsed/refractory disease is only 10 percent.

Uproleselan is an experimental, first-in-class E-selectin antagonist. 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.

GlycoMimetics has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration and Breakthrough Therapy designation from the Chinese National Medical Products Administration for uproleselan as a potential treatment for adult AML patients with relapsed or refractory disease.

The randomized, double-blind, placebo-controlled phase 3 clinical study evaluated uproleselan in combination with MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine and idarubicin) in patients with R/R AML. Patients received either uproleselan or placebo for 8 days over 1 cycle of an induction and, if applicable, up to three cycles of consolidation. The primary endpoint of the study was overall survival without censoring for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission rate and remission rate. A total of 388 patients across 70 sites in nine countries were randomized 1-to-1 between treatment and placebo arms.

The NCI and the Alliance for Clinical Trials in Oncology are conducting an adaptive phase 2/3 study of uproleselan in adults with newly diagnosed AML who are 60 years or older and fit for intensive chemotherapy. The randomized, controlled study is 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.

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