EHA 2021 | Real-world data of voxelotor for SCD

I’m the medical director of a lifespan model, sickle cell disease program, in the state of South Carolina in the United States. And we care for about 450 individuals with sickle cell disease across the age spectrum. And our clinic, we were sensing that single agent modification with our historical medicine, hydroxyurea, was adding significant benefit, but still patients were having major issues with sickle cell disease. So, it was clear that modification with hydroxyurea alone was likely not going to be enough. That a new tool like that voxelotor that was FDA approved in late 2019. When we had a look at the Phase III data that came out of the HOPE trial, my patients, as well as our program was very excited about the opportunity to have a new tool, to potentially modify the disease by directly inhibiting hemoglobin S polymerization and therefore decreasing sickling in our patients. And so we had patients who were very excited about this novel therapy and we decided what we wanted to do in our study is really look at the response of our patients in our clinic to voxelotor in an agent, I mean a single institution, real-world setting, how are patients doing on voxelotor?

And so we, in this study, looked at 77 patients from the ages of 12 up to 70, who were treated with voxelotor at a minimum of 1.9 months. And I think the average duration of treatment was about 7, excuse me, was about 9 months and some patients had been treated as long as 15 to 17 months. We looked at those patients across the age spectrum at the indicated age of 12 and up, and then wanted to look at their response. So, in similar ways to the HOPE trial, we wanted to look at the hemoglobin response, the response in their decline in total bilirubin and their response in terms of decline in reticulocyte percentage. So, that’s what we looked at. And we saw very robust improvements in hemoglobin across the population. Really the mean increase in hemoglobin from baseline in our patient population was two gram per deciliter, which is even more robust than the HOPE trial data. Although we were able to put into practice, some of those things that worked in the HOPE trial for mitigation of side effects, like lowering the dose when necessary for a period of time until side effects resolved. So, I think there were some things that we did that made our patients potentially tolerate the medication very well.

We also saw very robust declines in reticulocyte percentage and in total bilirubin telling us that there was a decline in homolysis in our patients as those are surrogate markers. We saw the most robust responses in patients who had a baseline hemoglobin less than 10 gram per deciliter. And that would make sense since those patients have a bone marrow that’s revved up and ready to respond as soon as they decrease the sickling. Although the patients who had a baseline greater than 10 gram per deciliter in their hemoglobin also showed responses in terms of rise in hemoglobin.

We also measured patient and clinician measures of improvement that were validated. And in those measures of improvement, we saw that the majority of patients were much improved or very much improved on both the clinician and the patient reported validated surveys. And that those improvements seemed to correlate with the improvement in their hemoglobin and the decline in their homolysis parameters.

The clinicians that are taking care of patients with sickle cell disease would be excited to see the fact that at least in our view, in our single institution data, there seems to be a complimentary effect of the combination of hydroxyurea and Oxbryta. And of course, we need further studies and larger groups than our patient size of 77. But I think what we’re seeing here is that patients responding to voxelotor with improvements in hemoglobin, decline in bilirubin and percent retic, we know in the short run that that’s directly related to a decrease in sickling. And that should be exciting to all of us who take care of individuals with sickle cell disease. Knowing the crux of the problem is that change in the shape of the red cell, that leads to all the downstream damage to the body.