Voxelotor for Sickle Cell Disease

Voxelotor (previously called GBT440), is being developed as an oral, once-daily therapy for patients with sickle cell disease (SCD). Voxelotor is designed to work by helping hemoglobin, the molecules inside red blood cells, hold onto more oxygen as the red blood cells travel through the body. This keeps red blood cells in their normal shape and helps stop sickling.

In our ongoing clinical development program, we are evaluating the impact of voxelotor on abnormal polymerization of deoxy-hemoglobin, the underlying mechanism of red blood cell sickling. We believe that this mechanism is potentially relevant for all patients with SCD and have designed a clinical program targeted at the treatment of SCD patients across all ages and genotypes.

In recognition of the critical need for new treatments, the U.S. Food and Drug Administration (FDA) has granted voxelotor both Fast Track, Orphan Drug and Rare Pediatric Disease designations for the treatment of patients with SCD. The European Medicines Agency (EMA) has included voxelotor in its Priority Medicines (PRIME) program, and the European Commission (EC) has designated voxelotor as an orphan medicinal product for the treatment of patients with SCD.

About SCD

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.

Sickle Cell Disease (SCD)

Who SCD Affects:
There are 90,000 to 100,000 SCD patients in the U.S., 60,000 SCD patents in Europe, and millions worldwide. SCD is a congenital disease, and symptoms and organ damage begin within the first years of life. This makes newborn screening (required in all states in the U.S.) and pediatric development of new therapeutics critical. Approximately one in 365 African American children in the U.S. is born with SCD and the global incidence of SCD is estimated to be 250,000 to 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 new treatment options are desperately needed.

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 recent 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.

Clinical Studies

We are currently enrolling patients for our Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study. The HOPE Study will evaluate whether voxelotor will be effective in reducing the damage sickle cell disease causes to red blood cells and therefore, decrease the day-to-day symptoms in adults and adolescents who have the disease.

We are also studying voxelotor in patients 6-17 years of age in the Phase 2a HOPE-KIDS 1 Study.