Sickle Cell Disease: Diagnoses, Screening, and Treatment - Episode 7
Peter Salgo, MD: Let’s take a look now at various therapies we haven’t mentioned that are in the pipeline being evaluated. What’s out there?
Biree Andemariam, MD: There’s a lot out there.
Peter Salgo, MD: OK, help me.
Biree Andemariam, MD: I think we’re really excited.
Jane Hankins, MD, MS: Yes.
Biree Andemariam, MD: We mentioned so far, the first FDA-approved drug 21 years ago, hydroxyurea. In 2017, the second drug was approved by the FDA. It’s L-glutamine, also known as Endari. And then at the tail end of 2019, we got 2 new drugs approved within 10 days.
Peter Salgo, MD: Let’s go over both of them.
Biree Andemariam, MD: Crizanlizumab is a monoclonal antibody that binds to P-selectin, and newer data that have come out of some basic science and translational work over the last decade-and-a-half, maybe longer, have shown us the importance of P-selectin in mediating the vaso-occlusive process.
Peter Salgo, MD: What does it actually do? How effective is it? There’s a trial out there, the SUSTAIN trial. What’s that all about?
Biree Andemariam, MD: Well, that’s been completed. I don’t know if somebody else wants to….
Sophie Lanzkron, MD, MHS: Yes. The SUSTAIN trial was a phase 2 randomized controlled trial that broke up into 3 groups—high dose, middle dose, and a placebo. And this is an IV [intravenous] infusional drug, and it demonstrated that it decreased crisis frequency from about 3 to 1-1/2 times in a year, so almost a 50% reduction in crisis frequency.
Peter Salgo, MD: And crisis meaning pain.
Sophie Lanzkron, MD, MHS: Pain.
Peter Salgo, MD: What about, did it look at that other silo of progressive chronic end organ failure?
Sophie Lanzkron, MD, MHS: No, we don’t have any data yet as to whether it has an impact on progressive disease.
Biree Andemariam, MD: There are trials designed to look at that question, including in kidney disease.
Sophie Lanzkron, MD, MHS: Correct.
Peter Salgo, MD: So that’s ongoing.
Jane Hankins, MD, MS: It’s ongoing, yes.
Elliot Vichinsky, MD: It’s exciting in that like hydroxyurea, similarly in terms of pain events, it lowered pain events, and having them on hydroxyurea added to the decrease. So, if you already were on hydroxyurea and you gave them this drug, they had a further decrease in events. And so that’s exciting. The issues with this drug are so far, the data show no effects on hemoglobin or laboratory findings with it. It did have a clinical response in pain events, but the biologic markers that you follow like CBCs [complete blood counts] and reticulocyte counts were not changed.
Jane Hankins, MD, MS: It’s hard to monitor.
Sophie Lanzkron, MD, MHS: Which suggests that the fact that the combination therapy works suggests that the first-line therapy for people with SS disease should remain hydroxyurea. Although in the study with crizanlizumab they did, it’s the only one where they’ve enrolled patients who had variant disease like SC disease. And it appeared to have an effect even in those individuals as well.
Peter Salgo, MD: And my own personal bias, based on what I’ve just heard, going back to what we discussed in the beginning since it has no effect on CBC, there’s a lot else going on in this disease.
Jane Hankins, MD, MS: That’s right.
Peter Salgo, MD: It’s just not CBC measurable.
Elliot Vichinsky, MD: I think we all would agree though that we should maximize our physicians’ recommendations first, maximize appropriate use of hydroxyurea.
Jane Hankins, MD, MS: Yes, absolutely.
Elliot Vichinsky, MD: And that would be our first-line choice before. Now there are obviously reasons to not use that, but it should not be ignored.
Transcript edited for clarity.