New Sickle Cell Medication Shows Promise

In adults with sickle cell disease, a new oral sickle hemoglobin inhibitor is well tolerated, according to data presented at the American Society of Hematology’s 2021 Annual Meeting. In healthy volunteers, the mean preliminary percentage of hemoglobin occupancy after a dose of 1400 mg was 25%, which exceeded that reported for voxelotor.

To test the hypothesis that the oral, small-molecule, next-generation sickle hemoglobin (HbS) inhibitor GBT021601 would safely and substantially reduce erythrocyte hemolysis and increase hemoglobin, the researchers conducted 2 studies.

The studies included a randomized, double-blind, placebo-controlled, parallel group, phase I study in healthy volunteers aged 18 to 55 years. Active medication doses in this study ranged from 50 to 2200 mg, and 39 of its 63 participants completed this study.

The researchers also conducted a single-arm study of a single-dose and multiple ascending doses in 6 patients aged 18 to 60 years who were homozygous for HbS sickle cell disease. The single dose given in this study was 100 mg, followed by multiple ascending doses given to achieve a percentage hemoglobin occupancy of at least 20% to 30% over 7 weeks.

Primary endpoints for both studies were safety and tolerability, and secondary endpoints included pharmacokinetics and pharmacodynamics. 

The researchers found that the medication was generally well tolerated; no deaths had occurred, most adverse events were grade 1 or 2, and there were no adverse events indicating tissue hypoxia. The pharmacokinetics of the medication were linear, and the medication was highly partitioned into erythrocytes. 

According to the researchers, “GBT021601 has the capacity to achieve a targeted [hemoglobin] occupancy and attain the desired hematological effect at low doses, therefore reducing pill burden and improving clinical outcomes for individuals living with [sickle cell disease].”

—Ellen Kurek

Reference:

Brown RC, Redfern A, Lisbon E, Washington C, Agodoa I, Smith-Whitley K. GBT021601, a next generation HbS polymerization inhibitor: results of safety, tolerability, pharmacokinetics and pharmacodynamics in adults living with sickle cell disease and healthy volunteers. Paper presented at: American Society of Hematology’s 2021 Annual Meeting; Atlanta, Georgia; December 11-14, 2021. https://ash.confex.com/ash/2021/webprogram/Paper152924.htm