GlycoMimetics, Inc. announced comprehensive results from its pivotal Phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). The study revealed a clinically meaningful improvement in median overall survival (mOS) for patients with primary refractory AML treated with uproleselan.
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. The primary endpoint was overall survival (OS). A total of 388 patients were randomized 1:1 between treatment and placebo arms across 59 sites in nine countries.
Key Findings
In the intent-to-treat (ITT) population (n=388), the mOS was 13.0 months for the uproleselan arm, compared to 12.3 months for the placebo arm (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.69-1.15), which was not statistically significant. However, a significant benefit was observed in the primary refractory subgroup.
For primary refractory patients, the mOS in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58; 95% CI 0.37-0.91) for the placebo arm (n=66). This benefit was irrespective of backbone chemotherapy. The median duration of response (DoR) for complete remission (CR) was not reached for primary refractory patients in the uproleselan arm compared to a median DoR of 12.7 months for the placebo arm.
Additional Data
- Backbone Chemotherapy: For patients treated with uproleselan plus FAI (n=98), mOS was 30.2 months compared to 12.8 months (HR 0.73; 95% CI 0.50-1.06) for patients treated with FAI alone (n=96) in the ITT population.
- Transplantation Status: For patients who received hematopoietic stem cell transplantation (HSCT) after study treatment, mOS was not reached for patients in the uproleselan arm (n=101).
- Secondary Endpoints: 36.1% of patients in the uproleselan arm (n=194) experienced CR at the end of induction (EOI), compared to 33.5% of patients in the placebo arm (n=194).
Safety Profile
Adverse events were consistent with the known safety profile for backbone chemotherapy regimens. 35.9% of patients in the uproleselan arm experienced serious treatment-emergent adverse events (TEAEs) compared to 34.2% in the placebo arm.
Ongoing and Future Plans
GlycoMimetics is advancing discussions with the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology for a Phase 2/3 study of uproleselan with chemotherapy in older adults with frontline AML. The company plans to engage with regulators and NCI to discuss potential paths forward for uproleselan.
"In the primary refractory setting, uproleselan’s improvement of mOS and greater duration of remission were particularly compelling, as there is a significant unmet need for new treatment options in this setting that can extend and improve the lives of patients," said Daniel DeAngelo, M.D., Ph.D., Professor of Medicine, Harvard Medical School, Chief, Division of Leukemia, Dana-Farber Cancer Institute, and Principal Investigator of the pivotal Phase 3 study.
Harout Semerjian, Chief Executive Officer of GlycoMimetics, added, "As we have analyzed data from this large, well-balanced, and well-executed study alongside medical, statistical, and regulatory experts, it has become clear that uproleselan may offer clinically meaningful patient benefit in multiple settings, including primary refractory AML."
