'There is a wealth of data across large subsets of this pivotal Phase 3 study that help us understand how prespecified stratification factors such as backbone chemotherapy, disease status, and age impacted survival outcomes for patients,' said
'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,' said
Results of Pivotal Phase 3 Study of Uproleselan in R/R AML
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 induction and, if applicable, up to 3 cycles of consolidation. The primary endpoint was overall survival (OS), which was not censored for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission (CR) rate and CR with partial hematologic recovery (CRh). A total of 388 patients in nine countries were randomized 1:1 between treatment and placebo arms. There were 59 sites that enrolled at least one patient. Median follow up was over three years at the time of primary analysis.
Overall Survival
Primary Endpoint: mOS in the intent-to-treat (ITT) population (n=388) 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); this difference is not statistically significant.
Disease Status
Primary Refractory: mOS for primary refractory patients 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.
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.
Early Relapse: mOS for early relapse patients in the uproleselan arm (n=28) was 3.7 months, compared to 6.4 months (HR 1.50; 95% CI 0.69-3.27) for the placebo arm (n=22).
Late Relapse: mOS for late relapse patients in the uproleselan arm (n=104) was 15.4 months, compared to 18.2 months (HR 1.10; 95% CI 0.77-1.57) for the placebo arm (n=106).
Backbone Chemotherapy
FAI: mOS for patients treated with uproleselan plus FAI (n=98) 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.
MEC: mOS for patients treated with uproleselan plus MEC (n=96) was 8.7 months compared to 12.3 months (HR 1.06; 95% CI 0.75-1.51) for patients treated with MEC alone (n=98) 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). In contrast, for HSCT patients in the placebo arm, mOS for patients receiving FAI (n=53) was 26.3 months and for patients receiving MEC (n=46) was 24.4 months.
Secondary Endpoints
7.2% of patients in each arm (n=388) experienced induction emergent severe oral mucositis.
36.1% of patients in the uproleselan arm (n=194) experienced CR at the end of induction (EOI) as determined by an independent endpoint review committee (IERC), compared to 33.5% of patients in the placebo arm (n=194).
46.4% of patients in the uproleselan arm experienced CR/CRh at EOI as determined by IERC, compared to 41.2% of patients in the placebo arm.
Post-treatment HSCT rate was 52.1% in the uproleselan arm and 51.0% in the placebo arm.
Subsequent AML therapy in non-responders was 40.0% in the uproleselan arm (n=80) and 46.2% in the placebo arm (n=78).
Safety
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.
85.9% of patients in the uproleselan arm experienced grade 3 or higher TEAEs compared to 87.6% in the placebo arm.
NCI Phase 2/3 Study of Uproleselan in Frontline AML
In addition to the company's pivotal Phase 3 trial of uproleselan, the
About AML
AML is the most common acute leukemia in adults. A cancer of the bone marrow, nearly 21,000 people in
About Uproleselan
Discovered and developed by
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Forward-Looking Statements
This press release contains forward-looking statements. These forward-looking statements may include, but are not limited to, statements regarding the conduct of, and timing for analysis and presentation of data from, clinical trials; potential development and regulatory activities and the potential benefits and impact of uproleselan. Actual results may differ materially from those described in these forward-looking statements. Forward-looking statements speak only as of the date of this release, and
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