GBT440

About Sickle Cell Disease

Sickle cell disease (SCD) is a chronic, inherited blood disorder that impacts hemoglobin, a protein found in red blood cells (RBCs) that carries oxygen throughout the body. The disease is caused by a genetic mutation in the beta-chain of hemoglobin, which results in the formation of abnormal hemoglobin known as sickle hemoglobin (HbS).  

In its deoxygenated state, HbS has a propensity to polymerize, or bind together into long, rigid rods within an RBC, much like a "sword within a balloon." As a consequence, the normally round and flexible RBC becomes rigid and elongated into a “sickled” shape. Polymerization causes the destruction of RBCs, known as hemolytic anemia. In addition, sickled RBCs, which do not flow properly in the bloodstream, clog small blood vessels and reduce blood flow to the organs. This results in inadequate oxygen delivery, or hypoxia, to all body tissues.

 

Who SCD Affects:

There are approximately 100,000 SCD patients in the U.S., 60,000 SCD patents in Europe, and millions worldwide. Children are a significant segment of the SCD population, and newborn screening is required at birth in the U.S. Approximately one in 500 African American children in the U.S. is born with SCD and the global incidence of SCD is estimated to be 250,000 – 300,000 births annually. The disease is concentrated in populations of African, Middle Eastern and South Asian descent.

Among children with SCD, roughly 10–15 percent will suffer an overt stroke. Many more will experience one or more silent strokes, which are associated with brain damage and cognitive impairment.


The Need for New SCD Treatments:

SCD represents a global health problem, and a treatment capable of halting disease progression is desperately needed. Hydroxyurea, initially approved as a cytotoxic chemotherapy agent for leukemia, is currently the only FDA-approved drug for SCD. However, the treatment is significantly limited by its side effects, variable responses, and concerns of long-term toxicity. Many SCD patients undergo chronic blood transfusions and very few patients are candidates for stem cell transplantation due to its significant risks, complexity, cost, and a limited supply of matched donors.

Beginning in early childhood, SCD patients suffer unpredictable and recurrent episodes or crises of severe pain due to hypoxia (inadequate oxygen delivery to body tissues) and hemolytic anemia (the destruction of RBCs). This can lead to multi-organ damage and early death. A 2014 publication noted that in the United States, SCD results in a decrease of approximately 25 to 30 years in life expectancy.

SCD is also associated with high treatment costs. One study estimated that in the United States, the average annual cost for the care of an adult patient with the most common genotype of SCD exceeds $200,000. This equates to cumulative lifetime costs in excess of $8.0 million over an assumed 50-year lifespan, driven primarily by hospital admissions, physician fees, clinic and emergency department visits, and the costs of diagnostic procedures and outpatient consultations.