GBT is developing GBT440 as a potential disease-modifying therapy for SCD.
"We are pleased to initiate our Phase 2a study of GBT440 in adolescents. The initiation of this study in adolescent SCD patients is an important milestone toward our goal of developing GBT440 for patients of all ages and genotypes," said Ted W. Love, M.D., chief executive officer of GBT.
"GBT440 has the potential to be a well-tolerated, once-daily therapy to address the underlying pathology of SCD rather than just treat the symptoms. We believe it could be particularly impactful in these young patients before much of the irreversible damage associated with SCD occurs."
About the Phase 2a GBT440-007 Study
GBT440-007 is an open-label, single and multiple dose study that is evaluating the safety, tolerability, pharmacokinetics and exploratory treatment effect of GBT440 in adolescents age 12 to 17 years with SCD. The study is being conducted in two parts: in Part A, six subjects will receive a single dose of GBT440, and in Part B, 24 subjects will receive multiple doses of GBT440 for up to 28 days.
The primary objective of Part A is to characterize the pharmacokinetics of GBT440 and the primary objective of Part B is to explore the safety of multiple doses of GBT440 administered to adolescent SCD patients.
About GBT440
GBT440 is being developed as an oral, once-daily therapy for patients with sickle cell disease (SCD). GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes GBT440 blocks polymerization and the resultant sickling of red blood cells (RBCs). With the potential to restore normal hemoglobin function and improve oxygen delivery, GBT believes that GBT440 may be capable of modifying the progression of SCD.
The U.S. Food and Drug Administration (FDA) has granted GBT440 both Fast Track and Orphan Drug designation for the treatment of patients with SCD in recognition of the critical need for new treatments.
GBT440 is currently being evaluated in the ongoing Phase 1/2 GBT440-001 study. This randomized, placebo-controlled, double-blind, single and multiple ascending dose study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of GBT440 in both healthy subjects and patients with SCD.
About Sickle Cell Disease (SCD)
Sickle cell disease (SCD) is an inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, leading to formation of abnormal hemoglobin known as sickle hemoglobin, or HbS. In its deoxygenated state, HbS has a propensity to polymerize, or bind together forming long, rigid rods within a red blood cell (RBC).
The polymer rods deform RBCs to assume a sickled shape and to become inflexible, which can cause blockage in small blood vessels. Beginning in childhood, SCD patients suffer unpredictable and recurrent episodes or crises of severe pain due to blocked blood flow to organs, which often lead to psychosocial and physical disabilities. This blocked blood flow, combined with hemolytic anemia (the destruction of RBCs), can eventually lead to multi-organ damage and early death.