Voxelotor, a first-in-class drug, is currently being studied for the treatment of sickle cell disease in the United States and Europe that has received Breakthrough Therapy Designation (BTD) by the… Click to show full abstract
Voxelotor, a first-in-class drug, is currently being studied for the treatment of sickle cell disease in the United States and Europe that has received Breakthrough Therapy Designation (BTD) by the Food and Drug Administration (FDA) and the European Medicines Agency Priority Medicines (PRIME) designation. As of December 2017, there are three published manuscripts on preclinical data regarding voxelotor. One describes discovery of the potent allosteric effector of HbS that has a high affinity for hemoglobin, allowing for therapeutic concentrations to be achieved in the erythrocyte with low serum concentrations. A second reports voxelotor prevents sickling of sickle cell trait red blood. Finally, a third that shows in the HbSS Townes knock-in sickle mice voxelotor extends the half-life of erythrocytes, reduces reticulocyte counts, and prevents ex vivo sickling. To date, three clinical trials evaluating voxelotor in individuals with sickle cell disease are either actively recruiting participants or have recently closed to accrual. The phase I randomized, placebo-controlled, double-blind, single and multiple ascending dose study of the tolerability and pharmacokinetics of GBT440 in healthy subjects and patients with SCD (GBT440-001; NCT02285088) is actively following participants but is closed to enrollment. The phase 2a, open-label, single and multiple dose study to evaluate the pharmacokinetics, safety, tolerability, and exploratory treatment effect of GBT440 in pediatric participants with SCD (HOPEKIDS1; NCT02850406) and the phase 3 randomized, placebocontrolled, double-blind, parallel group, multicenter study of participants, age 12–65 years, with SCD (HOPE; NCT03036813) are both actively enrolling participants. Eight meeting abstracts and presentations have reported preliminary clinical safety and efficacy data from these trials which are applicable to the concerns raised by Hebbel and Hedlund.
               
Click one of the above tabs to view related content.