GlycoMimetics Presents New AML Data with Uproleselan at 60th ASH Annual Meeting
- Data in relapsed/refractory and newly diagnosed acute myeloid leukemia (AML) patients underscore clinical opportunities across multiple outcomes measures and subgroups
- Selective disruption of bone marrow microenvironment with uproleselan resulting in high remission rates; majority of evaluable patients achieving stringent level of measurable residual disease (MRD) negativity; promising survival outcomes across all AML subgroups assessed
- Correlative studies further strengthen scientific rationale for inhibiting E-selectin in patients with AML, particularly those individuals with high-risk disease
Additionally, an analysis of E-selectin ligand expression on leukemic cells demonstrated that detectable levels are present in every patient tested, providing strong clinical evidence of biological relevance in this disease setting. In bone marrow blasts, leukemic stem cell expression of E-selectin ligand correlated with leukemic blast E-selectin ligand expression (p<0.0001), consistent with the hypothesis that E-selectin-mediated interactions are a mechanism of chemoresistance. Additionally, investigators assessed the association between baseline E-selectin ligand expression and clinical outcomes using a log-rank test. In the R/R cohort of patients (n=22), this analysis demonstrated that ≥10% E-selectin ligand expression at baseline is correlated with prolonged survival (p<0.01) for patients treated with uproleselan. This observation is important since separately Chien et al. (Abstract 1513) report that high levels of E-selectin ligand in patients not treated with uproleselan correlate with worse clinical prognosis.
“The new MRD and correlative efficacy data in difficult-to-treat
patients, when combined with the already encouraging response rate and
survival results from this trial, further demonstrate the potential of
uproleselan to be an important new treatment option in AML,” said Daniel
J. DeAngelo, M.D., Ph.D., Chief of the
“It is now clearly established that patients with AML who express
E-selectin ligands on their leukemic cells have more infiltrative,
aggressive disease and significantly worse clinical outcomes when not
treated with uproleselan,” said
The ASH presentations referenced above include:
Publication Number: 331
TITLE: Uproleselan (GMI-1271), an E-Selectin Antagonist, Improves the Efficacy and Safety of Chemotherapy in Relapsed/Refractory (R/R) and Newly Diagnosed Older Patients with Acute Myeloid Leukemia: Final, Correlative and Subgroup Analyses
Publication Number: 1513
TITLE: E-Selectin Ligand Expression by Leukemic Blasts Is Associated with Prognosis in Patients with AML
1 Feldman et al, J Clin Oncol. 2005 Jun 20;23(18):4110-6.
2 Greenberg et al, J Clin Oncol. 2004 Mar 15;22(6):1078-86.
3 Lowenberg et al, N Engl J Med. 2009 Sep 24;361(13).
4 Lancet et al, Blood. 2014 May 22;123(21):3239-46.
About Uproleselan (GMI-1271)
Uproleselan (yoo’ pro le’sel an) is designed to block E-selectin (an
adhesion molecule on cells in the bone marrow) from binding with blood
cancer cells as a targeted approach to disrupting well-established
mechanisms of leukemic cell resistance within the bone marrow
microenvironment. In a Phase 1/2 clinical trial, uproleselan was
evaluated in both newly diagnosed elderly and relapsed/refractory
patients with AML. In both populations, patients treated with
uproleselan together with standard chemotherapy achieved better than
expected remission rates and overall survival compared to historical
controls, which have been derived from results from third party clinical
trials evaluating standard chemotherapy, as well as lower than expected
induction-related mortality rates. Treatment in these patient
populations was generally well tolerated, with fewer than expected
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discovery and development of novel glycomimetic drugs to address unmet
medical needs resulting from diseases in which carbohydrate biology
plays a key role.
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