GMI-1070 is being developed in partnership with Pfizer to treat vaso-occlusive crisis of sickle cell disease (VOC). The compound is a synthetic glycomimetic molecule, which was rationally designed to inhibit all three selectin types (a pan-selectin inhibitor). Selectins are glycoprotein cell adhesion molecules implicated in inflammatory processes. To achieve adequate therapeutic activity in certain inflammatory disorders, inhibition of all three selectin types (E-selectin, L-selectin and P-selectin) may be required. We therefore believe that GMI-1070’s ability to inhibit all selectins will provide distinct advantages over other approaches that target only one selectin, or which are so broadly active as to be non-specific.
GlycoMimetics has selected vaso-occlusive crisis (VOC) of sickle cell disease as the first indication to explore with GMI-1070. Inflammation is a key mediator of vaso-occlusive crisis, a condition which represents a significant unmet medical need. Sickle cell disease is one of the most prevalent genetic disorders in the U.S., affecting over 90,000 people. It is a chronic condition causing substantial illness and death. For example, VOC is responsible for more than 70,000 hospitalizations per year in the U.S. with an average stay of approximately six days. GMI-1070 has received both Orphan Drug and Fast Track status for VOC from the U.S. Food & Drug Administration (FDA).
The main clinical feature of sickle cell disease is periodic painful VOC episodes, known as VOC or pain crises, which result in significant clinical complications. Treatment for VOC today consists primarily of supportive therapy, in the form of hydration and pain control, typically requiring extended hospitalization. No other therapies have been effective in aborting a VOC once it has begun. GMI-1070 is intended to treat VOC by inhibiting the cell activation and enhanced cell adhesion which causes the ischemia and pain.
In January 2013, GlycoMimetics, Inc. announced completion of enrollment in a Phase 2 sickle cell disease study with GMI-1070. The randomized, double-blinded study examined the efficacy, safety and pharmacokinetics of GMI-1070 in hospitalized sickle cell disease patients experiencing VOC. GlycoMimetics enrolled 76 patients ages 12 to 60 at 22 trial sites in the United States and Canada. The company reported topline data from the trial in April 2013.
In December 2012 at the American Society of Hematology Annual Meeting, researchers shared data from a pilot study of GMI-1070 via an oral presentation, which was entitled, “Pan-selectin Antagonist GMI-1070 Affects Biomarkers of Adhesion, Activation and the Coagulation Cascade in Sickle Cell Patients at Steady State.” Data from the study demonstrated that GMI-1070 affects a number of biomarkers important in sickle cell disease, including some known to be involved in VOC.
In late September 2010, GlycoMimetics announced the publication in Blood of preclinical data showing effects of GMI-1070 in an animal model of sickle cell crisis. These preclinical studies demonstrate significant promise for the compound in sickle cell crisis.
Expanding Applications for GMI-1070
GMI-1070 may have a number of additional potential applications, including hematologic cancers in which selectins may play a significant role. Selectin-mediated cell adhesion may result in chemotherapy resistance. Selectins have also been shown to facilitate dissemination of cancer cells to bone marrow. Initial evidence from preclinical blood cancer studies shows that GMI-1070 prevents selectin-mediated cancer cell adhesion and thereby renders cancer cells more sensitive to chemotherapy.
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