Rivipansel (GMI-1070)

Rivipansel 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 rivipansel’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 conducted a Phase 2 randomized, double-blinded study examining the efficacy, safety and pharmacokinetics of rivipansel 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 and presented full data from the clinical trial in two oral presentations and one poster presentation at the December 2013 meeting of the American Society of Hematology (ASH.) One of the oral presentations was selected a “Best of ASH.”

In the Phase 2 trial, patients treated with rivipansel experienced reductions in time to reach resolution of VOC, length of hospital stay and use of opioid analgesics for pain management, in each case as compared to patients receiving placebo.

About VOC

GlycoMimetics selected vaso-occlusive crisis (VOC) of sickle cell disease as the first indication to explore with rivipansel. 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. Rivipansel 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. Rivipansel is intended to treat VOC by inhibiting the cell activation and enhanced cell adhesion which causes the ischemia and pain.

In December 2012 at the ASH Annual Meeting, researchers shared data from a pilot study of rivipansel 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 rivipansel 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 rivipansel in an animal model of sickle cell crisis. These preclinical studies demonstrate significant promise for the compound in sickle cell crisis.

Expanding Applications for Rivipansel

Rivipansel 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 rivipansel prevents selectin-mediated cancer cell adhesion and thereby renders cancer cells more sensitive to chemotherapy.