The U.S. Food and Drug Administration (FDA) granted GBT440 fast track, orphan drug, and rare pediatric disease designations for the treatment of SCA. In addition, the European Medicines Agency (EMA) has included GBT440 in its priority medicines (PRIME) program, and the European Commission (EC) has granted the drug orphan drug designation for the treatment of SCA.
How GBT440 works
GBT440 has the potential to selectively bind to hemoglobin, a protein found inside red blood cells that carries oxygen throughout the body. The investigational therapy specifically inhibits hemoglobin polymerization and the consequent sickling of red blood cells, the hallmark of SCA. In that way, it helps restore normal red blood cell function and oxygen distribution.
SCA is caused by a genetic mutation in the HBB gene that provides instructions for making a component of hemoglobin, resulting in the formation of abnormal hemoglobin called sickle hemoglobin (HbS).
HbS has a propensity to polymerize, or bind together, forming long, rigid rods within red blood cell. This causes red blood cells to become stiff and elongated into a sickle or crescent shape instead of their normally round and flexible shape. As a result, red blood cells do not flow properly in the bloodstream, reducing oxygen delivery to all of the body’s tissues.
GBT440 in clinical trials
GBT440 is currently being evaluated in four clinical trials for the treatment of SCA.
Phase 1 (NCT02285088) and Phase 2 (NCT03041909) clinical trials aim to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy people and people with SCA. Initial results showed an increase in hemoglobin and profound and durable reductions in hemolysis, or the rupturing of red blood cells and peripheral blood sickle cells. These data, together with prior data, further support the excellent safety and tolerability profile of GBT440.
To further demonstrate GBT440’s safety and capacity to modify the course of SCA, the drug is now being investigated in a Phase 2 study (NCT02850406) called HOPE-KIDS 1 in children and adolescents with SCA, and a pivotal Phase 3 study (NCT03036813) in children and adults with SCA, ages 12 and older. Both studies are currently recruiting patients.
The most common adverse events associated with the use of GBT440 was headache. There have been no serious adverse events that have been deemed to be drug-related. Decreases in erythropoietin, a hormone produced by the kidneys that promotes the production of red blood cells, and reticulocyte, or immature red blood cell, counts are consistent with improved oxygen delivery.
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