Rivipansel (GMI-1070) is a potential new treatment for the excruciating pain of vaso-occlusive crisis associated with sickle cell anemia. It is being developed by GlycoMimetics in partnership with Pfizer.

How Rivipansel works

Rivipansel is a pan-selectin inhibitor, a molecule that blocks the activity of cell adhesion molecules called selectins in the blood vessels.

Selectins are a family of three molecules (E-, P-, and L-selectin) that regulate interactions between cells within blood vessels and promote the adhesion of blood cells (white blood cells, platelets, and red blood cells) to the walls of blood vessels and to each other. For this reason, they are known as adhesion molecules.

In sickle cell anemia, there is an increased number of selectins inside blood vessels, which makes blood cells more prone to stick to surfaces and to other cells. This causes the clumping of blood cells with each other and their adherence to the blood vessel walls, reducing the inner space of blood vessels and obstructing blood flow, which in turn causes a severe attack known as sickle cell pain crisis.

Rivipansel binds to all three selectins (although mainly to E-selectin), preventing cell adhesion and pain crisis.

Rivipansel in clinical trials

The first study of Rivipansel in humans was a Phase 1 clinical trial that was conducted in 72 healthy volunteers. This study investigated what the drug does to the body (pharmacodynamics), what the body does to the drug (pharmacokinetics), and made a first estimate of the safe and maximum tolerable doses of Rivipansel that could be given to patients. Results were presented at the 2009 American Society of Hematology (ASH) Annual Meeting and showed no severe adverse effects associated with the treatment. One study participant had a pruritic skin rash while receiving the treatment, but this was resolved with treatment.

Another Phase 1 clinical trial (NCT00911495) was conducted in 15 patients with sickle cell anemia who were clinically stable. Patients received two infusions of Rivipansel. Results showed that the treatment was well tolerated and produced no significant adverse effects. They also showed that Rivipansel could decrease the levels of several biomarkers of cellular adhesion, such as E-selectin and P-selectin, in the blood.

A Phase 2 placebo-controlled clinical trial (NCT01119833) was then conducted at 22 study locations in the U.S. and Canada to examine the safety, effectiveness, and pharmacokinetics of Rivipansel in 76 hospitalized patients with sickle cell anemia with pain crisis. Results from this study were presented at the 2013 American Society of Hematology (ASH) Annual Meeting, and published in the scientific journal Blood. They showed that patients treated with Rivipansel experienced large reductions in the time to resolution of pain crisis, the use of opioid painkillers, and the length of hospital stay, compared with patients receiving placebo. These results supported the progression of the potential treatment to Phase 3 trials.

The Phase 3 RESET clinical trial (NCT02187003) started in June 2015 and is currently assessing the effectiveness and safety of Rivipansel for the treatment of pain crisis in hospitalized sickle cell anemia patients. This study expects to include about 350 patients, ages 6 and older, who will receive placebo or Rivipansel injected into a vein every 12 hours up to a maximum of 15 doses. The study is currently recruiting participants in 125 study locations throughout the U.S. and Canada.

Patients who complete this study will have the chance to enter a Phase 3 extension study (NCT02433158), which plans to include around 250 hospitalized patients with sickle cell anemia over 96 study locations in the U.S. and Canada. The purpose is to evaluate the long-term safety and effectiveness of Rivipansel.

Other information 

Rivipansel received orphan drug status and fast-track designation from the U.S. Food and Drug Administration (FDA), which will speed its approval process if it is shown to be effective. The goal is to allow patients to have faster access to treatment.

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