Last week, the Food and Drug Administration approved two new gene therapies to treat sickle cell disease. Roughly 100,000 people in the U.S. live with the debilitating and painful blood disorder, most of whom are African American. One of these “milestone treatments’' is a drug using powerful gene-editing technology never before approved for human use. It can repair a mutation that produces sickle-shaped red blood cells that can lead to stroke, organ damage and premature death.
But the millions of dollars the treatments cost is just one of the barriers facing patients like Jayla Eddins, a high school senior in Salem, and her mother, Jamie Eddins, who helps manage her daughter’s illness. Dr. Trisha Wong is an associate professor of pediatrics in the division of hematology and oncology at Oregon Health & Science University. They join us to talk about the physical and emotional toll of the disease as new breakthroughs emerge to treat it.
The following transcript was created by a computer and edited by a volunteer:
Dave Miller: From the Gert Boyle Studio at OPB, this is Think Out Loud. I’m Dave Miller. Roughly 100,000 people in the US live with sickle cell disease. Most of them are African American. Last week, the Food and Drug Administration approved two new gene therapies to treat the debilitating and painful blood disorder. One of these milestone treatments is the first-ever therapy approved by the FDA that uses the CRISPR gene editing tool. It repairs a mutation that produces sickle shaped red blood cells that can lead to stroke, organ damage and premature death. We’re going to hear about the disease and these new treatments today. Jayla Eddins is a 17-year old high school senior in Salem who has sickle cell disease. She joins us now along with her mother, Jamie. Trisha Wong is with us as well. She’s a pediatric hematologist/oncologist at Oregon Health Science University (OHSU). Welcome to all three of you.
All: Thank you.
Miller: Jamie, first. When did you find out that Jayla has sickle cell disease?
Jamie Eddins: I found out pretty early I had sickle cell disease when I was actually still pregnant. Her father told me that he had the trait and I knew I had it. So when I was going to my prenatal care, they had me talk to a genetic counselor and they suggested for me to have some fluids taken out of my stomach so they could test to see if Jayla would have sickle cell. And they ended up calling me and letting me know that she had sickle cell so I was well aware while I was pregnant that she had sickle cell disease.
Miller: Can you give us a sense for your family history of the disease?
Jamie Eddins: My father had sickle cell disease. I have a cousin who has sickle cell disease. My father passed away from sickle cell.
Miller: How old was he?
Jamie Eddins: I think he was 34-years old.
Miller: How old were you then?
Jamie Eddins: I believe I was 12.
Miller: So given that history, what went through your mind when you heard that your daughter had it as well?
Jamie Eddins: I was pretty scared because I have a cousin that’s around my age so I remember her going into the hospital a lot and her having a lot of restrictions and things she couldn’t do. And I guess that my fear of my daughter is that she would just have so many restrictions and things she can’t do. And it scares me.
Miller: Jayla, how have you been doing healthwise over the last year or so?
Jayla Eddins: I’ve been doing good for the most part. I mean, I’ve been having some crises here and there, but besides that I’ve been doing OK.
Miller: Some crises here and there? What’s a crisis?
Jayla Eddins: For me, it just kind of happens if I don’t take my medicine or something or even if I do take my medicine, it’s a pulsing type of pain for me.
Miller: Posting?
Jayla Eddins: Pulsing.
Miller: Pulsing type of pain?
Jayla Eddins: Yeah. Like your heartbeat. How it’s repetitive. That’s how my pain is.
Miller: And where might it be sometimes?
Jayla Eddins: Well, most times if it’s small and it goes away, it’s in my neck, but recently it’s been in my back and my stomach region.
Miller: How bad can the pain get?
Jayla Eddins: Really bad. If it doesn’t go away and it’s there and it doesn’t stop, I have to go to the hospital or I just can’t do anything. I’ll have to still lay down. If I move a certain way, it’ll hurt more. If I stay a certain way it’ll hurt less. So it just depends.
Miller: Do you have any warning or any idea when there’s going to be a crisis or does it just come out of nowhere?
Jayla Eddins: It just comes out of nowhere.
Miller: Wherever you are, whenever it might be. What are good days like?
Jayla Eddins: Good days are just normal. I go to school or I just go home. It’s just how any other person would spend their day.
Miller: Trisha Wong, can you describe why the disease got the name sickle cell?
Trisha Wong: Yes, it’s a description that was described in 1910. And under a microscope, the cells look like sickles or when we describe it to a six year old, it’s banana-shaped.
Miller: I just realized you have a t-shirt, a sickle cell t-shirt but that looks more like a butterfly.
Wong: Yeah, it does. But on the wings are sickles.
Miller: So wait. What are red blood cells supposed to look like? How does this shape lead to severe health problems?
Wong: So the way I describe it to med students and again, patients, too, is that a cell should be like a water balloon: squishy, round. It can flex and bend through different blood, small blood vessels. But in sickle cell, the hemoglobin has a mutation that makes the hemoglobin stick end on end to each other. So they stack up and form polymers or think of it as a water blue now shoved with toothpicks and skewers. And that’s going to both elongate and misshapen the cells into that sickle patho pneumonic sickle shape and it is rigid now and it causes a log jam in the smallest blood vessels in the capillaries. And when you don’t get blood flow to certain tissues and they sense that starving-oxygen need. That’s where the pain sets in and then over decades, that’s how you get organ damage and the strokes and the kidney failure.
Miller: What is the range of symptoms that come from this disease? You’re talking about so many different body systems and differences. So, what’s the range of how it affects the body?
Wong: There are different types of sickle cells. So there are some that are pretty mild and they live almost pretty normal lives. And sickle cell trait is [in] one in 13 Black [people] in the United States and they live almost completely normal lives and that’s the genetic carrier state that leads to sickle cells. So, Jamie has sickle cell trait, but sickle cell disease, again, is a spectrum, too. But so some are mild and very rarely affected the most severe though and especially as you age, it gets a little bit more severe. They can be on disability and not working and have had strokes. Their thoughts are pervaded by pain and it’s just hard to carry on jobs and relationships when you’re always feeling pain.
Miller: Jayla, you said that when things are really bad, you’ve ended up in the hospital. How often does that happen? How common is that for you?
Jayla Eddins: Well, I think maybe two to three years ago I got put on like a medication that keeps my hemoglobin really up. So I haven’t been in as many crises as I used to before. Maybe this year I probably had big ones. I probably have maybe two to three, but I have a lot of small ones too.
Miller: Jamie, you’ve got the long perspective here from when Jayla was just an infant. What was it like when she was really little in terms of the health care scares and being a parent to a very sick baby?
Jamie Eddins: So with her first crisis, she was about six months old and I remember they had to do a spiral tap on her because she was crying, she had a fever. I was a single parent at the time so I kind of had to deal with it by myself and just seeing your five-month old baby screaming and stuff getting a needle in their back, it was pretty rough. And then they said that she still had the I think of hemoglobin still. I guess all her sickle cell wasn’t really always there yet.
Miller: There were still some of the healthy-shaped red blood cells from fetal blood…
Jamie Eddins: Yeah.
Miller: Meaning, things were going to get worse in terms of the progression of the disease?
Jamie Eddins: So then from there after six months, we were going to the hospital maybe every two to three weeks. She has spleen issues. I think I became an expert at checking her spleen because it feels like the tip of your nose, but her spleen kept being enlarged. She had several different blood transfusions. I think in her first year of life, we probably were in the hospital about 12 times and it wasn’t like short visits. It was maybe a week or two weeks in the hospital. I think she got her first surgery when she was two years old when her spleen was removed, but she was on chronic transfusions for every two weeks because she was still underweight and they couldn’t do the surgery to remove her spleen until she met weight.
Miller: Jayla, what has living with sickle cell meant for what school life is like?
Jayla Eddins: Well, it really depends. I just got to a new school. So basically I have a 504 and…
Miller: What’s a 504?
Jayla Eddins: It’s kind of basically like a plan. So if I get sick or if I need anything, the teachers know what to do. So, I gave that to the nurse. I also make the teachers aware of what I have, what’s going to happen and some teachers know about it. Some don’t. So it’s kinda, it really just depends on how it goes. If I do have a sickle cell crisis, which I haven’t had much of this year, but when I usually do have a sickle cell crisis, like I’ll tell the teacher and I’ll lay down cause I usually try to go to sleep to pass by time to see if it goes away. If it doesn’t, then I’ll take some medication for it, but I’ll lay down or I’ll go to the nurse and lay down and see if it goes away. It just depends, or I try to walk it off because sometimes, depending on where the pain is, walking it off makes the pain reduce.
Miller: You said you’re in a new school now. My understanding is that you moved to Salem from Philadelphia last year. So from a much bigger city and from a city with a much higher African American population and a much higher population of both people with sickle cell and doctors who treat it or teachers who have kids who have it. I imagine much more awareness in Philly of sickle cell than in Portland, let alone Salem. It’s hard to read your smile right now, but it doesn’t look like a totally happy smile. What has that meant?
Jayla Eddins: It’s just funny when I think about it because of how they treat it. The hospitals here are OK/ Well, I mean, OSHU is much more knowledgeable about sickle cell, which is, I’m really grateful for…
Miller: More so than when you were seeking care in Salem, a bigger academic city hospital.
Jayla Eddins: They had no clue. The doctor who had me, the first one, didn’t even know what medication some of the new medication I was on was. I was his first patient with sickle cell. He didn’t know anything. And when I did get admitted to the hospital, I didn’t really get much care either. So they, literally, like they saw that I had a fever. They saw I was sick and what and when they found out the cause - like I think I had COVID - they just sent me home and they gave me some medicine and I was still sick for like a week or two.
Jamie Eddins: Yeah, I had to actually push him to do a CBC to check her hemoglobin level. That was like…
Miller: A blood test is a complete blood count?
Jamie Eddins: Yeah. Just to see her hemoglobin level because I don’t know at that particular time she had COVID or not, but it’s still, it’s like a standard thing because what’s coming from CHOP…
Miller: Children’s Hospital of Philadelphia.
Jamie Eddins: Yeah. Children House of Philadelphia.
Miller: You’re testing all my acronym knowledge. I think I’m out of it now.
Jamie Eddins: It’s a pretty standard thing for a child coming here with a sickle cell crisis or pain that they will do a blood count and chest x-ray. And then, I guess the other determinations are if they have flu or anything but that is pretty standard with Children’s Hospital in Philadelphia. When we went to the hospital in Salem, I was like, “hey, are you going to check her hemoglobin level?” “Well, we just know it’s COVID.” But you still need to check it because her stuff could be really, really low because she looking pale. It is like one of those standard things and so it’s a little scary. And I told Jayla and stuff, because she is getting older, she had to be an advocate for herself when she is in a situation like that when I’m not around for the standard of care that you used to.
Miller: Dr. Wong, I want to turn specifically to the issue of race. As I noted at the beginning, the vast majority of people around the world who have sickle cell disease are of African descent. How do you think, in the US, that has affected the way the medical establishment has approached the diagnosis of this disease, the treatment of it and research money for it?
Wong: In my humble opinion, very profoundly. I do think, I mean, if you compare to cystic fibrosis and hemophilia, which are other inherited diseases that affect a much more diverse, therefore more Caucasian population, they have been able to be loud and proud and they’ve advocated for themselves. And I think companies and scientists have gravitated to those diseases and treating them and coming up with cures and diagnostic testing and sickle cell didn’t have that for decades. And I think it was largely because of how they’re perceived by the medical establishment. That’s my opinion. And I do see that, if a hemophilia patient comes in and says I need 1000 units of ADVATE, nobody questions them. If a patient with sickle cell comes in and says I need two grams of Dilaudid, everybody’s questioning them.
Miller: Wait, that’s pain medication?
Wong: Yes, a pain medication. So yes, there is a stigma to opioids and there needs to be some amount of thinking about opioids before you just prescribe it. But also if it is the right medication for a patient, we would like them to be believed to say I have 10 out of 10 pain. I need treatment.
Miller: And certainly we’ve heard over the years, many studies have found that when Black patients interact with the medical system, their pain is discounted in ways that white patients’ pain is not.
Wong: Yes, it’s actually been published and I hope that study has been disproven in the past in the intervening decades. But yes, there’s actually been studies that have shown Black [people] tolerate pain better, which is not true.
Miller: So Trisha Wong, let’s turn to these new treatments. What was your reaction?
When you heard the final news, there had been sort of incremental progress towards it. I’m sure you were aware of it. Well, before many of us knew about this sort of incremental progress. But last week in the big news, the FDA said yes to these two new treatments. What went through your mind?
Wong: It was my first thought because we knew the packets had been submitted, but we were not expecting anything until, I was thinking January. But Friday was also the first day of our American Society of Hematology giant meeting in San Diego. So I think maybe the timing was to hit the big meeting announcement, but it was excitement. It was unknown. It was, “oh, there’s going to be a lot of logistics to figure out.” It was quickly to look up at the package insert to figure out what it was approved for. Obviously, the approvals were based on clinical trials and there was very strict eligibility criteria for those clinical trials. And FDA, what they market it for, sometimes follows it exactly. And sometimes they change it a little bit. So that was my first thought, who’s going to be able to get this?
Miller: What is the therapy, especially the CRISPR one, going to entail?
Wong: They’re about both the same in that a patient who is qualified and insurance approval– and that’s going to be a whole another ball game–would come in and get their own peripheral blood collected that is riched for stem cells. The stem cells are going to be shipped to a very high tech…
Miller: Let me see if I even understand that part. So, but over weeks…
Wong: Over weeks, yeah.
Miller: My understanding is because there isn’t that much of these stem cells in a pint of blood, so over time, a patient would donate their own blood…
Wong: You get a medication to kind of stimulate stem cells and then you can get it collected, ideally in one shot. But we have learned that you have to undergo one to four collections of stem cells.
Miller: And then those get sent to a lab somewhere.
Wong: Yeah. And it’s a high tech manufacturing plant actually. And I always joke that they’re in New Jersey for some reason.
Miller: And then what happens?
Wong: They get manipulated - very high tech. And this is the science that’s been happening for 20 years. They get manipulated to the point where the stem cells and specifically the DNA in the stem cells are manipulated so that the hemoglobin is not sticky. So if I said at the beginning, the mutation is that the hemoglobin sticks end to end. So it just does it, it makes it unsticky. Is that a word? Unsticky. And then it’s frozen and shipped back to the patient’s bedside and when the time is right, the patient undergoes chemotherapy very high doses of chemotherapy to empty out their sickle stem cells and then these manipulated, treated stem cells are re-infused over the next three weeks. They set up shop, they hone into the bone marrow, and then you can slowly start seeing these back-to-being round squishy cells emerging from the bone marrow.
Miller: So basically, your own stem cells are taken out and then re-engineered in a way using this gene editing technology to make the healthy red blood cells and then that stuff is put back inside your body. And ideally, and this has been shown in the trials, then you’ll make healthy shaped cells. How is the process of putting the gene editing stem cells back in your body, different from the existing bone marrow transplant protocol? Is it that different?
Wong: The beginning part is not all that different and then after you get the infusion, it’s not that different. But what does save having to find a match to donor - a bone marrow transplant requires you to have as close of a match as possible - and people of different ethnicities other than Caucasian have a much harder time finding a match bone marrow. So it takes away having to find a matched bone marrow donor. And then after years, months later, there’s something called graft versus host that when you’re not exactly matched, the graft can cause chronic health problems. So it takes away that because it’s your own stem cells.
Miller: Even though it’s been edited, your body still recognizes it as it’s close enough that it’s not graft versus host, it’s host and host.
Wong: Exactly.
Miller: Let’s turn to the price though because the reports I’ve seen say that these two treatments, the sticker price is $2 million or $3 million, a mind boggling sum. But I also don’t know if it’s a real number. Is insurance going to pay for that?
Wong: I think that’s the hope. And there are some programs set up and I am not a health economist, but there are some programs set up that if it doesn’t work, the insurer will get paid back by the manufacturer. So that’s kind of in the works. That’s a novel model in health care. And $2 million, my understanding is just the product that’s not going to include the three weeks admitted to the hospital and the four collections of stem cells that go ahead of time.
Miller: Oh, so it could be hundreds of thousands of dollars more.
Wong: A million more maybe.
Miller: So always add a zero when in doubt, when we’re talking about the American healthcare system?
Wong: It’s probably a fair suggestion.
Miller: Who do you think is going to qualify for this? From what I understand, another huge wrinkle here is just very few centers currently and none in Portland, the closest is in Seattle, are authorized to do this. And there could be a real logjam at the factories themselves, that they’re very limited so far just in terms of the number of stem cells that they can edit right now. Which means that even if money weren’t an issue, this is sort of resource limited. So who’s going to qualify for this?
Wong: Medicine is always a little bit, the squeaky wheel gets the oil. So I do think it’s going to be the more vocal people who are advocating with their insurance to get it. It probably will start in the big centers who have a higher sickle cell population so Children’s Health Hospital of Philadelphia, Atlanta, Oakland will probably be the highest priority. And then we are hopeful that there’s no reason why somebody who happens to live in Oregon should have less access to these. So it is our intention to get qualified, but we are just not at the top of the priority list.
Miller: But that is your hope at some point to have OHSU be on the list.
Wong: Yes, that is definitely my hope. And we have talked to both manufacturers. So that is again, as I think, a reasonable, a cautious hope.
Miller: Jayla what went through your mind when you heard about this treatment that’s now been approved?
Jayla Eddins: I was kind of curious about it. I know my mom talked to me about it and me and my friends talked about it as well.
Miller: Friends who also have sickle cell?
Jayla Eddins: Yeah. So back in Philly, there’s a couple camps for people who have sickle cell and then they put us all in one big camp and then we go somewhere for a week and then come back to CHOP.
Miller: What’s it like to be around people where you don’t have to explain yourself?
Jayla Eddins: It’s nice. We have many things in common. A lot of them have the same type of sickle cell I have. So we kind of share our experiences, share the same things we do with each other. But besides that, we just have fun. It’s nice.
Miller: You’re just friends, too.
Jayla Eddins: Yeah.
Miller: So was there excitement among your friends when you shared this news or questions?
Jayla Eddins: Some of them were questioned about it. Some of them didn’t really like the idea of it because they were kind of suspicious of editing genes. Yeah. So it’s a lot of, unless some of them were not even sure if it was like a real thing. So it’s more confusion than excitement than anything.
Miller: Tricia Wong, that all makes sense to me. I mean, this is the very first approved treatment from the federal authorities that uses this particular technology. The other one is a still new but already approved gene editing technology. But what kinds of conversations do you think you’re going to have with your patients in the coming years?
Wong: Yeah. Right now, we have patients who are already reaching out and interested in how to get into this. So I think there are families who are ready to go and “sign me up.” “Where do I need to go and where do I need to sign?” And so that population who’s been following it and certain a little bit. But even then, we have to just be a little bit more honest and real and bring them down more into a realistic realm that this is not going to be…We’re not quite calling these cures yet. I do see lay people calling this cure. I think we’re more calling this a transformative therapy as opposed to curative because the CRISPR one we’ve only been studying for three to four years. We don’t know what the long term effects are. So transformative is a term we’re using now. So we don’t want people going in thinking this is a cure and walking in the park.
Then there’s other people who have lots of questions and unsure and not even sure this is real. So we’re hoping we also have a much smaller foundation for people living with sickle cell to have like a ZOOM so we can answer all these questions together and have a little bit more of a hopefully open safe conversation about what we think. But also as a provider, I have to be very careful about not leading anybody one way or another.
Miller: Jamie, earlier, when you were talking about going to the hospital for the first time when you moved to Oregon, you said you’re trying to remind Jayla that she now needs to be her own advocate because you’re not going to be there always. I mean, it does remind me that Jayla is a senior. So you’re dealing with something that so many parents deal with, getting ready to have their kids leave the nest. I’m wondering what happens when you layer sickle cells on top of that?
Jamie Eddins: Well, I know Jaya’s looking for certain schools. So I tell her if she’s going to go to college that’s near a hospital that treats people with sickle cell, for example, go to a climate friendly state if she plans to leave Oregon. Because with sickle cell, if you’re too hot, that can put you into a sickle cell crisis. If you’re too cold, that can put you in a sickle cell crisis. So I don’t wanna try to limit her, but I’m telling her the reality of things. Go to a place where you’re less likely to have a weather-related crisis, in a place that can treat you.
Miller: That you’re in a place that knows where you’re not the very first sickle cell patient that a doctor has seen.
Jamie Eddins: Exactly.
Miller: Jayla, What are your hopes for next year?
Jayla Eddins: Well, I’m still looking at some colleges. I’m honestly really not sure what’s going to come up for next year. I’m not sure if I’m going to stay with my mom and go to college where she’s going to go or if I’m going to go to a different college somewhere else and have to stay on my own. So I really don’t know how next year is going to be.
Miller: Well, Jayla and Jamie Eddins, thanks very much for coming in.
Jamie Eddins: Thank you.
Jayla Eddins: Thank you.
Miller: And Tricia Wong, thank you as well.
Wong: Thank you.
Miller: Trisha Wong is a pediatric-hematologist oncologist at OHSU. Jayla and Jamie Eddins joined us as well. Jayla is a 17-year old high school senior in Salem. Her mother is Jamie Eddins.
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