Selecting and Utilizing Newer Therapies in SCD

Ify Osunkwo, MD, MPH: Now we have 3 FDA-approved drugs.

Julie Kanter, MD: Four.

Ify Osunkwo, MD, MPH: Four?

Julie Kanter, MD: Four FDA-approved drugs, hydroxyurea, Endari….

Ify Osunkwo, MD, MPH: Oh, that’s right, I forgot hydroxyurea. So now we have 4 FDA-approved drugs. And we now have to think about for each patient, who may have overlapping pathophysiological mechanisms in play, how do you treat them optimally? Hydrea will give you some benefit, Endari will give you some benefit, voxelotor will give you some benefit, crizanlizumab will give you some. Do you use them in combinations, single agents? What do we think the future of therapy for sickle cell disease is going to look like in the next 5 years?

Nirmish Shah, MD: I’ll go ahead and say right now, I think it was good that the trials had patients, two-thirds of their patients both in HOPE and SUSTAIN, on hydroxyurea, basically proving that we are becoming an additive-therapy type of situation. I’ll start the conversation because I think this is going to go awhile because I don’t think we have the right answer yet. I think we’re regarding sickle cell disease as a chronic disease finally.

Julie Kanter, MD: A lifespan disease.

Nirmish Shah, MD: It’s a lifespan chronic disease just like congestive heart failure, diabetes. We use multiple medications to address different aspects of that disease, which is where we’re getting now. I think we’re going to start with triaging patients to say, “Well, what is the major issue here that I have to address, and then can I layer on more medications to add to what we have?”

Ify Osunkwo, MD, MPH: To get to that best-case scenario. It may change depending on the phase of life of the patient, right?

Julie Kanter, MD: Absolutely.

Ify Osunkwo, MD, MPH: They may not need hemoglobin to be high when they’re [age] 10, but when they’re 45 with the EPO [erythropoietin] level that’s very low, that may be something that would be much more beneficial to the patient.

Julie Kanter, MD: We may find that the hemoglobin modifiers have more difference when they’re younger because as they have accumulated damage over time, their blood vessels get damaged.

Ify Osunkwo, MD, MPH: And we can’t reverse that.

Julie Kanter, MD: Well, we don’t know completely if you can reverse it. We know in cardiovascular conditions, if individuals with severe cardiovascular disease change their diet, lose weight, exercise, they can improve their vascular condition. We don’t know this yet. We hope something like crizanlizumab, which may reduce some of that stickiness to the blood vessels, could decrease some of that vasculopathy. We don’t know. I think having the option of a red cell agent like voxelotor and something like crizanlizumab targeting 2 different mechanisms could be really useful.

Ify Osunkwo, MD, MPH: With hydroxyurea and looking at Endari as well.

Julie Kanter, MD: Absolutely.

Ify Osunkwo, MD, MPH: I think they were both approved, for age 12 and older was….

Julie Kanter, MD: Voxelotor.

Biree Andemariam, MD: Crizanlizumab was age 16.

Ify Osunkwo, MD, MPH: Sixteen and older, and voxelotor was 12 and older.

Biree Andemariam, MD: Yes.

Ify Osunkwo, MD, MPH: We still have that gap for the younger patients between ages zero and 12, what to do with them. I think the studies that are ongoing right now may give us more information about those.

Nirmish Shah, MD: The excitement that came with hydroxyurea being started at 9 months and older is that we are being more preventive. What we’re seeing is complications are kind of being pushed downstream, and so maybe if we add voxelotor early, we could push even more issues downstream. I think that the concept you’re bringing up, Julie, about preventing issues is key.

Ify Osunkwo, MD, MPH: I do want to bring up here, before we move to the next section, the hemoglobin SC and S-beta-plus genotypes that were always thought historically as being milder forms of the disease, in pediatrics mostly, and now mostly kids live to be 18, 19, 20 years old. Then you begin to see the patients merge together and look alike. A 40-year-old with SC looks a lot like a 40-year-old with SS, and they have the same complication rate, the same mortality rate, and it’s really important that we don’t continue to look at those genotypes as mild forms of the disease. Again, these drugs are approved to also serve all genotypes, like crizanlizumab.

Julie Kanter, MD: It’s also important that in pediatrics especially, I’ve noticed a lot of the 12-, 13-, 14-year-olds with SC, S-beta-plus, those were the ones more likely to get lost.

Ify Osunkwo, MD, MPH: Lost to follow-up, yes.

Julie Kanter, MD: They stop following up in their young teens.

Ify Osunkwo, MD, MPH: They’ve always been healthy, so they don’t need their hematologist anymore or their primary care doctor.

Julie Kanter, MD: Right. But when they come in, they can be incredibly sick. Multi-organ failure syndrome is actually more common in those genotypes. We really want to make sure that those individuals continue following up when they’re young so they get in that habit.

Transcript edited for clarity.