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.
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.
For more information about our sickle cell disease clinical study program visit www.GBTSickleCell.com.
Click here to access information about the Phase 3 HOPE Study on ClinicalTrials.gov.
Click here to access information on the Phase 2a HOPE-KIDS 1 Study on ClinicalTrials.gov.
Mechanism of Action
Abstracts & Presentations
59th American Society of Hematology Annual Meeting & Exposition (2017)
- Oral Presentation
Initial Results from a Cohort in a Phase 2a Study (GBT440-007) Evaluating Adolescents with Sickle Cell Disease Treated with Multiple Doses of GBT440, a HbS Polymerization Inhibitor - Oral Presentation
Opioid Utilization Patterns in United States Patients with Sickle Cell Disease - Poster Presentation
A Single Center Experience of GBT440 Treatment of Severe Anemia in Sickle Cell Disease (SCD) - Poster Presentation
The Pharmacokinetics (PK) of GBT440 Following Single Doses in Pediatric Patients with Sickle Cell Disease (SCD) - Poster Presentation
Quality of Care in United States Children with Sickle Cell Anemia - Poster Presentation
GBT1118 Diminishes Vaso-Occlusion in Sickle Cell Disease Mice - Poster Presentation
Access to Care for Medicaid and Commercially-Insured United States Patients with Sickle Cell Disease
SCDAA 45th Annual National Convention (2017)
- Oral Presentation
Profound Clinical Benefit in a Patient with Severe, Transfusion-refractory Anemia Treated with GBT440 through Compassionate Use
Academy for Sickle Cell and Thalassemia 11th Annual Conference (2017)
- Poster Presentation
Efficacy of GBT440 in a Patient with HbSC Genotype Sickle Cell Disease - Poster Presentation
The Pharmacokinetics (PK) of GBT440 are Similar in Adolescents and Adults with Sickle Cell Disease
22nd Congress of the European Hematology Association (2017)
- Poster Presentation
Abstract #P620
The Pharmacokinetics (PK) of GBT440 Are Similar in Adolescents and Adults with Sickle Cell Disease (SCD)
58th American Society of Hematology Annual Meeting & Exposition (2016)
- Poster Presentation
Abstract #2488
Long-Term Dosing in Sickle Cell Disease Subjects with GBT440, a Novel HbS Polymerization Inhibitor - Poster Presentation
Abstract #4760
The 9-Item Sickle Cell Disease Severity Measure (SCDSM): A Novel Measure of Daily SCD Symptom Severity Developed to Assess Benefit of GBT440, an Experimental HbS Polymerization Inhibitor - Poster Presentation
Abstract #2487
Absorption, Metabolism, and Excretion of GBT440, a Novel Hemoglobin S (HbS) Polymerization Inhibitor for the Treatment of Sickle Cell Disease (SCD), in Healthy Male Subjects
European Hematology Association’s (EHA) 21st Congress (2016)
- Poster Presentation
Abstract# P371
GBT440, a Novel HbS Polymerization Inhibitor, Increases Hb Oxygen Affinity and Results in a Rapid Improvement in Hemolysis and Anemia - Poster Presentation
Abstract# P370
Pharmacokinetics (PK) and Pharmacodynamics (PD) of GBT440, a Novel Hemoglobin S (HbS) Polymerization Inhibitor for the Treatment of Sickle Cell Disease (SCD), in Healthy Volunteers and SCD Patients
10th Sickle Cell Disease Research and Educational Symposium (2016)
- Poster Presentation
GBT440, a novel HbS polymerization inhibitor, increases Hb oxygen affinity and results in a rapid improvement in hemolysis and anemia.
57th American Society of Hematology (ASH) Annual Meeting (2015)
- Oral Presentation
Abstract #542
GBT440, a Potent Anti-Sickling Hemoglobin Modifier Reduces Hemolysis, Improves Anemia and Nearly Eliminates Sickle Cells in Peripheral Blood of Patients with Sickle Cell Disease - Poster Presentation
Abstract #2172
GBT440 Demonstrates High Specificity for Red Blood Cells in Nonclinical Species
56th American Society of Hematology (ASH) Annual Meeting (2014)
- Oral Presentation
Abstract #217
GTx011, a Potent Allosteric Modifier of Hemoglobin Oxygen Affinity, Prevents RBC Sickling in Whole Blood and Prolongs RBC Half-Life in Vivo in a Murine Model of Sickle Cell Disease - Poster Presentation
Abstract #1370
GTx011, an Anti-Sickling Compound, Improves SS Blood Rheology By Reduction of HbS polymerization Via Allosteric Modulation of O2 Affinity
55th American Society of Hematology (ASH) Annual Meeting (2013)
- Oral Presentation
Abstract #316
GTx011, a Potent Allosteric Modifier of Hemoglobin Oxygen Affinity, Delays Polymerization and Prevents Sickling - Poster Presentation
Abstract #2207
GTx011, a Novel Agent that Improves Rheological Properties of Sickle Cell Blood by Increasing Oxygen Affinity for Hemoglobin