GlycoMimetics Shares Complete Phase 3 Results for Uproleselan in R/R AML

GlycoMimetics, Inc., a biotechnology company specializing in glycobiology-based therapies for cancer and inflammatory diseases, has unveiled detailed results from its Phase 3 study evaluating uproleselan in relapsed/refractory acute myeloid leukemia (R/R AML). This pivotal study assessed the effectiveness of uproleselan in combination with chemotherapy, comparing it to a placebo.

Key results from the trial indicate a considerable median overall survival (mOS) advantage for patients with primary refractory AML treated with uproleselan. In this subgroup, patients on the uproleselan arm experienced a mOS of 31.2 months, significantly higher than the 10.1 months observed in the placebo group. These figures suggest that uproleselan could fulfill a critical unmet need for new therapeutic options in primary refractory AML, potentially extending and enhancing patient survival.

The Phase 3 study was robust, involving 388 patients from nine countries who were randomized in a 1:1 ratio to receive either uproleselan or a placebo alongside standard chemotherapy regimens, specifically MEC (mitoxantrone, etoposide, and cytarabine) or FAI (fludarabine, cytarabine, and idarubicin). The primary endpoint of the study was overall survival, with secondary endpoints including the incidence of severe oral mucositis, complete remission rates, and the duration of response.

For the intent-to-treat (ITT) population, the overall mOS was 13.0 months for the uproleselan arm versus 12.3 months for the placebo arm, a difference that was not statistically significant. However, when stratified by disease status, the benefits of uproleselan were more pronounced in primary refractory patients. The uproleselan arm's mOS was 31.2 months compared to 10.1 months for the placebo arm, regardless of the chemotherapy backbone used.

In early relapse patients, the uproleselan arm showed a mOS of 3.7 months versus 6.4 months for the placebo, whereas late relapse patients had a mOS of 15.4 months with uproleselan compared to 18.2 months for the placebo. These variations underscore the complexity of AML and suggest that uproleselan may be particularly beneficial for certain patient subsets.

The study also found that the adverse events (AEs) associated with uproleselan were consistent with the known side effects of the chemotherapy regimens used. A significant proportion of patients in both the uproleselan and placebo arms experienced serious treatment-emergent adverse events (TEAEs), with 35.9% in the uproleselan group and 34.2% in the placebo group.

On the secondary endpoints, the incidence of severe oral mucositis was identical between the two arms at 7.2%. Complete remission (CR) rates at the end of induction (EOI) were slightly higher in the uproleselan arm (36.1%) compared to the placebo arm (33.5%). Additionally, the rate of complete remission with partial hematologic recovery (CRh) was 46.4% for the uproleselan arm, compared to 41.2% for the placebo.

The trial's results have prompted GlycoMimetics to engage with the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology to discuss a potential Phase 2/3 study of uproleselan in older adults with newly diagnosed AML. This study aims to evaluate the addition of uproleselan to standard chemotherapy regimens.

Uproleselan, a first-in-class E-selectin antagonist, disrupts the interaction between leukemic cells and the bone marrow microenvironment, enhancing the effectiveness of AML treatments. It has received Breakthrough Therapy and Fast Track designations from the FDA and similar recognition from Chinese regulatory bodies.

GlycoMimetics continues to leverage its specialized glycobiology platform to develop transformative treatments for diseases with high unmet needs, aiming to improve patient outcomes in AML and other cancers.