Pfizer enrolls first patient in phase III sickle cell disease trial
Pfizer has announced that the first patient has been enrolled in the RESET (Rivipansel: Evaluating Safety, Efficacy and Time to Discharge) study—a phase III clinical trial assessing the efficacy and safety of rivipansel for the treatment of vaso-occlusive crisis in hospitalized individuals with sickle cell disease who are 6 years of age or older.
Sickle cell disease is one of the most prevalent genetic disorders in the U.S. It is a rare and debilitating chronic disease with lifelong clinical impact and reduced life expectancy; life expectancy is 48 years for females and 42 years for males with sickle cell disease. There are more than 100,000 people in the U.S. living with sickle cell disease, and many of them experience multiple vaso-occlusive crises each year. These painful crises result in more than 75,000 hospitalizations per year in the U.S., with an average hospital stay of approximately six days.
The phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study is planning to enroll at least 350 people with sickle cell disease, aged 6 and older who are hospitalized for a vaso-occlusive crisis and will evaluate the efficacy and safety of treatment with rivipansel. Study participants must be receiving treatment with intravenous opioids for their vaso-occlusive crisis and must be able to receive the first dose of study drug within 24 hours of initiation of intravenous opioid therapy.
The primary endpoint for the study will be time to readiness-for-discharge. Key secondary endpoints will include time to discharge, cumulative IV opioid consumption and time to discontinuation of IV opioids.
Rivipansel (GMI-1070) is an investigational pan-selectin inhibitor. Selectins are a family of molecules believed to play a key role in regulating cellular interactions within blood vessels. Rivipansel is not a narcotic or a pain medication.
The intense pain associated with sickle cell vaso-occlusive crisis is believed to be due to local tissue ischemia consequent upon blockage occurring in microvascular beds and capillaries. This results from occlusion or clogging of vessels with sickled red blood cells (which become rigid and inflexible when sickled) and subsequent, selectin-driven adhesion of white blood cells (leukocytes) to the inner wall of the blood vessel (endothelium) and the recruitment of platelets; events which collectively restrict blood flow.
In 2011, Pfizer entered into a worldwide license agreement with GlycoMimetics for the development and, if approved by applicable regulatory authorities, commercialization of rivipansel. GlycoMimetics was responsible for development up to phase II and Pfizer will be responsible for all future clinical development of rivipansel.
The start of the phase III trial triggered the second of two milestone payments from Pfizer to GlycoMimetics totaling $35 million for phase III initiation. GlycoMimetics received a $15 million milestone payment from Pfizer in May 2014.
Rivipansel has received Orphan Drug and Fast Track status from the FDA, and this study is being conducted under a Special Protocol Assessment (SPA), in agreement with the FDA.