Rivipansel (GMI-1070) was a potential new treatment for vaso-occlusive crisis associated with sickle cell anemia. It was developed by GlycoMimetics in partnership with Pfizer, but failed to meet its treatment goals in a clinical trial. The results of the trial will be published to inform future studies.

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 each other. This causes the clumping of blood cells and their adherence to the blood vessel walls, reducing the inner space of blood vessels and obstructing blood flow, which then causes a severe attack known as a vaso-occlusive crisis or 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. That study investigated what the drug does to the body (pharmacodynamics), and what the body does to the drug (pharmacokinetics). The trial also 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 side 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 the treatment was well-tolerated and produced no significant side 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) then was 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 of resolution of pain crisis, the use of opioid painkillers, and the length of hospital stay, compared with patients receiving a placebo. Those results supported the progression of the potential treatment to Phase 3 clinical trials.

A Phase 3 clinical trial (NCT02187003) called RESET began in June 2015 and further assessed the effectiveness and safety of Rivipansel for the treatment of pain crisis in hospitalized sickle cell anemia patients. The study included 345 patients, age 6 and older, who received placebo or Rivipansel injected into a vein every 12 hours, up to a maximum of 15 doses. The study assessed whether treatment reduced the time patients had to be in the hospital, and whether treatment with Rivipansel decreased opioid use for pain management.

However, the trial failed to meet either outcome measurement. In a press release, Pfizer indicated that the full results of the trial will be published in order to inform future trials.

Other information 

Rivipansel received orphan drug status and fast-track designation from the U.S. Food and Drug Administration (FDA) based on promising early data. 

 

Last updated: Aug. 7, 2019

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