Experts look into what is next for sickle cell disease and provide key thoughts on the space.
Ifeyinwa Osunkwo, MD, MPH: What else is out there? We have hydroxyurea. We have voxelotor, crizanlizumab, Endari, transfusions. What’s next? There’s a plethora of treatment options to treat the variety of patients who have who have sickle cell disease. We’re stuck with 4 or 5 options. What else is in the pipeline to treat sickle cell disease?
Patrick McGann, MD, MS: If we had this conversation 5 years ago, it wouldn’t be much of a conversation. It’s a good time to be in sickle cell, and the future is bright. Gene therapy, despite the issues, is there. There are many ways to do that. As someone had mentioned, science will prevail with time. The curative options are there, but it’s important to recognize that they’re not going to be there tomorrow, and they’re not going to be there next year for the masses.
There are a number of other therapies out there. Fetal hemoglobin is out there. Fetal hemoglobin is a good target. We know about BCL11A. There are groups trying to make fetal hemoglobin higher using a medication that is in development, and I’m sure there are many ways that’s being tried. There’s a class of medications, called PKR activators, that were designed for pyruvate kinase deficiency. It’s is a very small population, but they can be repurposed to reduce hemolysis in sickle cell disease in ways not too unsimilar to voxelotor. Crizanlizumab is medicine that targets P-selectin.
Several other medications in that class are in development or are being repurposed to see if they can address pain. Because even though we’re trying to address the root cause, when a patient comes with pain, what can you do to abort that pain? We have nothing, except for opiates, which are not the solution. It’s a tough battle, but there are efforts trying to do that with P-selectin and all selectins, and many ways with inflammation. But there are many classes. This is a bigger conversation than it could have been even a couple of years ago. It’s an exciting time, and we’ll get to a point where sickle cell disease treatment is a cocktail approach. You take a couple of things, and as long as we can work on it, if we can address things from different angles, then we’ll make our patients have better lives.
Ifeyinwa Osunkwo, MD, MPH: Absolutely. Well, thank you so much. This has been an amazing conversation. I want to thank Abdullah, Wally, and Pat. Before we close, tell the audience your 1 big dream, or 1 final thought, that you want everybody who sees or hears or takes care of patients with sickle cell disease to know as a takeaway message from this conversation. I’m going to start with Abdullah. Your 1 final word that you want them to know about?
Abdullah Kutlar, MD: As you said, this has been a really exciting conversation. Wally, you, and Pat contributed greatly. Considering this discussion, there are 2 things. It’s important, scientifically, to pursue curative options like gene therapy. I’ll repeat that science will prevail. We will have to overcome the risks, understand them better, and remedy them. That’s 1 thing.
Coming back to Wally’s point, we need more disease-modifying agents that we can use in Africa or India. The typical approach would be—I agree with Pat—new F-inducing agents or a combination of F-inducing agents. Maybe a combination of F-induction with some downstream modifications like anti-inflammatory or antiadhesion therapies. These are going to be important, and I believe these have to be pursued in sickle cell, along with these high-tech, higher-source modalities. This includes swallowing a pill, which can easily be conveyed to Africa or low-resource countries.
Ifeyinwa Osunkwo, MD, MPH: Thank you so much, Abdullah. I’m going to follow up with Wally. Wally, what are your 1 or 2 big-picture, take-home thoughts?
Wally Smith, MD: I’d like to put my public health hat on. I want our audience to know about a report that came out in November from the National Academies of Sciences, Engineering, and Medicine. Ify, you and your colleagues did wonderful preparing 512 pages about all that is wrong in sickle cell care in the United States and what needs to be done to make sickle cell care better. There were 7 pillars that you pointed out, and they had to do with education and social policy. They had to do with patient empowerment and disparities. You declared sickle cell to be a disparities disease, as Pat said earlier. They had to do with therapy as well. But it wasn’t just therapy that you focused on. You focused on social determinates of health, you focused on policy, racism, and changes in the fabric of the health care system, especially for adults with sickle cell. We don’t even have an adult sickle cell disease health care system. We have a shack instead of a home for adults with sickle cell disease. That’s the 1 thing I want to take away. None of this discussion we just had will matter is there’s nobody to care for the patients. And in many parts of the country, there’s nobody—doctor, nurse, or other—to care for these patients.
Ifeyinwa Osunkwo, MD, MPH: Very well said. Thank you so much, Wally.
Patrick McGann, MD, MS: I’m going to add to that because it’s so important. The names of the medicines don’t matter. Whether you live in Cincinnati, or Angola, or India, if we have good therapies, they should be available. We need to leverage that equity to global treatment of sickle cell disease. Hydroxyurea was developed in the 1980s and ’90s and is only now becoming available in Africa. Not really, even. I don’t want to give a talk when I’m retiring in a few decades telling patients about all these new therapies that we’re using in the United States and how sickle cell disease is history, except in Africa, where 90% of kids are still dying before they’re adults. That can’t happen. As these therapies are developed, by Bill Gates or whomever, we’re going to need a lot of people. We need to be sure that these are truly equitable in a timely manner, or we’re doing a huge disservice to the global sickle cell community.
Ifeyinwa Osunkwo, MD, MPH: Thank you so much. I’m going to give my thoughts. The first thing I want the audience to recognize is that sickle cell disease is a lifetime genetic disorder. It doesn’t go away when you become a teenager or when you leave pediatrics. It doesn’t disappear when you get married. It’s there for the rest of your life. It does shorten your life span.
The second thing is pain with sickle cell disease. It’s important, but it’s not the only important thing. Organ damage, that chronic, slow slump of devastation to the organs is a reality, and no patient will die because of pain. They will die from strokes, kidney disease, pulmonary hypertension, infection, heart problems, lung problems. It’s important to look at them as treating not just pain but the entire person. That entire person will also involve their quality of life. Ask them how they’re doing, how are they functioning. Do they get up and go to work? If not, why not? When you’re giving treatment, look at the impact of treatment. Not just on their pain, as we talked about, but on their overall quality of life.
We talked about screening for sickle cell disease at birth, screening for complications following the guidelines, and early intervention. For example, retinopathy picked up early can prevent blindness, treating hyposthenuria early prevents ESRD [end-stage renal disease], and picking up pulmonary hypertension can prolong life by putting the right treatment in place. But there’s also supportive care. And let’s not forget the role of the primary care provider. The last time I checked, having sickle cell disease does not protect you from getting breast cancer, colon cancer, high blood pressure, diabetes, or diverticulitis, or any other thing that anybody else gets. My patients have all this, and they deserve whole care—not sickle cell care but all-around holistic medical care.
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Transcript Edited for Clarity