Background:
Sickle cell disease (SCD) is an inherited disorder characterized by polymerization of sickle hemoglobin (HbS), leading to red blood cell (RBC) sickling, chronic hemolytic anemia, vaso-occlusive crises (VOCs) and cumulative organ damage. The investigational agent osivelotor (GBT021601) increases hemoglobin (Hb)-oxygen affinity and decreases the concentration of deoxygenated HbS tetramers, thus inhibiting HbS polymerization. It is currently being evaluated in an ongoing phase 2/3 trial, and previous reports of preliminary data from the 12-week, phase 2 portion have indicated that osivelotor was generally well tolerated in adults with SCD. Increased Hb and hematocrit, improvements in markers of hemolysis, as well as improved RBC deformability and decreased point of sickling on ektacytometry, were also reported. An initial biomarker analysis showed a reduction of adherent cells in a flow adhesion assay with vascular cell adhesion molecule 1 (VCAM-1).
Aims:
To report preliminary pharmacodynamic (PD) biomarker analyses in patients with SCD receiving osivelotor.
