Impact of Anemia & Hemolysis in Sickle Cell Disease - Episode 8

Using Voxelotor in SCD: Results From HOPE Study

September 9, 2021
Sophie M. Lanzkron, MD, MHS

Jeffrey D. Lebensburger, DO, MSPH

John J. Strouse, MD, PhD

Jeffrey D. Lebensburger, DO, MSPH, reviews data and key findings from the 72-week analysis of the HOPE study using voxelotor for patients with sickle cell disease.


Sophie Lanzkron, MD, MHS: The mechanism of action of voxelotor is really interesting. One of the key things about it is that it affects the upstream problem and prevents the sickling of red cells. If you prevent sickling of red cells, you’ll prevent downstream effects. It binds to the hemoglobin and increases hemoglobin’s affinity for oxygen, so the red cells stay oxygenated for a longer period of time, and as they go through the venous system, there’s less time in that setting where the cells are not oxygenated. The longer they spend oxygenated, the less likely they’re going to sickle. Because there’s less sickling, we see less hemolysis and an increase in hemoglobin.

Jeffrey Lebensburger, DO, MSPH: Voxelotor is newly FDA approved, and 1 of its goals is to increase the hemoglobin. There’s likely benefit to increasing hemoglobin. One concern that many of us had would be if we increased the hemoglobin, will we increase the risk of vaso-occlusive events? This is something the HOPE study looked to address in their 72-week analysis. Overall, the numbers were for the entire population about 2.8 pain events per year for those who were not on drug and about 2.4 events per year for those who are on the drug.

Then they did a secondary analysis, which said that if the goal of voxelotor is to increase the hemoglobin, then they looked to see whether patients stratified by hemoglobin level had a difference in vaso-occlusive events. When they stratified it by greater than 12 g/dL and hemoglobin 10 to 12 g/dL and so forth, what they found is those patients with the highest hemoglobins had the lowest incidence of vaso-occlusive events. The HOPE study initially was looking at the ability to raise the hemoglobin, but this would be the population that most of us clinically would be worried about. If we increased the hemoglobin level, in essence increasing the potential viscosity of blood, will those patients with the highest hemoglobin levels than develop more pain crisis? The HOPE study shows us that those were the patients who had the lowest number of pain events, so additional studies should be undertaken to prove that voxelotor will not increase vaso-occlusive crises.

The HOPE study published in The Lancet Hematology looked at the primary end point of a raise in hemoglobin, but they also looked at vaso-occlusive events in the first 24 weeks as well. It was a 3-arm study. Those who are in 1500 mg of voxelotor, 900 mg of voxelotor, and placebo in both the 1500 mg and the 900 mg had a lower incidence of acute vaso-occlusive events.

Transcript edited for clarity.