The Sickle Cell Disease Patient Journey - Episode 11

Patient Factors Associated With the Choice of SCD Therapy

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Wally Smith, MD, discusses the mechanisms of actions of various therapies for SCD and the patient factors associated with the choice of therapy.

Ifeyinwa Osunkwo, MD, MPH: I want you to go into a little more detail on the 3 specific medications, because many people don’t know they’re available. In layman’s terms, can you talk about how the medicines work? While comparing them with one another, tell us what the study showed, the common adverse effects that each drug has, and who would be a good candidate for the different drugs.

Wally Smith, MD: Sure. L-glutamine was approved in 2017. The patients in the study had on average 4 vaso-occlusive crises per year that required them to go to the hospital. L-glutamine decreased it on average to 3. You can give it to 6-year-olds and older. It’s a powder; you mix it up. It’s a protein, so you think of it as natural. You take it in powder form a couple of times per day. As long as you can tolerate that, there are very few adverse effects to it. Some people are turned off by the powder and having to take something as inconvenient as that. But it’s nice because you can give it to children. You can also give it on top of hydroxyurea. That was a real advance to be able to have people on more than 1 drug for their sickle cell disease.

In 2019, voxelotor and crizanlizumab were approved. Voxelotor, or Oxbryta, is a medication designed specifically to bind to hemoglobin and help the oxygen-carrying capacity of hemoglobin. By binding to stop the sickling process, It was created specifically for sickle cell patients. It was a designer drug. It was originally the 446 of 1000 compounds tested for its ability to bind and stay on the hemoglobin-oxygen complex. That drug has come to market. It decreases the amount of symptoms by having increases in hemoglobin. On average, it’s about 1 g or 1 blood unit transfused, but it can go as high as 3 or 4 g. Can you imagine walking around with a hemoglobin of 6 most of your life, getting on this drug, and your hemoglobin goes up to 10 g/dL? I’ve seen that. Voxelotor was a real advance.

Crizanlizumab, or Adakveo, is an infusion drug. It was working on the inflammation. The specific target is called selectin, and it’s a P-selectin inhibitor. It basically cuts down on the inflammation in your body and, therefore, decreases the vaso-occlusive crises. The patients in the trial had, on average, 3 vaso-occlusive crises in a year if they weren’t getting the drug and 2 in a year if they were getting the drug. People say, “That’s not much of an improvement.” No, that’s a huge improvement. One big change in not having to go to the hospital per year is an improvement. Anybody will tell you: 1 less hospitalization per year is meaningful.

These drugs are available now. They’re not cheap. Hydroxyurea is the only cheap 1. Insurance will cover them with a bit of red tape and manipulation. You can get insurance to cover them if you have insurance. Most patients who are on them are able to stay on them. There are a few adverse effects with each drug. We can go into those, but in general, they’re well-tolerated drugs. It’s certainly not like chemotherapy, which can make you lose your hair and do bad things to you.

We know for a fact that voxelotor is good at about 2 weeks. We know it can last as long as a year. We’ve had people on it that long, and the hemoglobin stays up for that whole period of time. About 2 weeks in, you get a rise in hemoglobin. Studies have shown that it stays up at about that level for as long as 72 weeks. With crizanlizumab, we’re starting to see studies past 1 year, but people were on it for a full year before the drug even came out to prove that it worked.

These drugs have been a tremendous advancement in what we have to offer patients. It takes me an hour to explain to patients the therapies available to them now. Ten years ago it took me 5 to 10 minutes. There are transfusions, hydroxyurea, and there’s what you’re used to: pain medicines, fluids, bed rest, etc. Patients have a hard time believing that there are all these drugs. We have to work to allay suspicions. Why are these drugs out? What took them so long? We have to explain to people that it took interest and it took money, and once we had those, science took care of our problem.

Ifeyinwa Osunkwo, MD, MPH: Thank you so much, Dr Smith. You’re right. It took interest and money, and then the science was always there. It just needed the interest and money to make it come to fruition.

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Transcript Edited for Clarity