This post was originally published on Sacramento Observer
By Genoa Barrow | OBSERVER Senior Staff Writer
The U.S. Food and Drug Administration (FDA) has approved two sickle cell treatments with curative potential. Longtime SCD physician Dr. Marcia Treadwell sat down with The OBSERVER to talk about the “transformative” gene therapies and what they mean for people living with sickle cell.
GENOA BARROW. The FDA recently approved two new gene therapies. What does that mean in layman’s terms?
MARCIA TREADWELL. The two FDA-approved gene therapies actually act a little bit differently. The first one is called Casgevy. When you’re in utero, in your mother’s womb, then you’re making what’s called fetal hemoglobin. As you get older and pass around six months or so, then you stop making fetal hemoglobin and start to make, in the case of a person with sickle cell disease, the hemoglobin S, and of course, when you have the two genes for sickle cell disease, then you have some very serious issues related to the vaso-occlusive episodes [crises] and increased risk of infection and so on.
The aim was really to stop that fetal hemoglobin from being what’s called “knocked out.” There’s a regulator that would make the fetal hemoglobin stop being produced normally. And what the Casgevy does, using the CRISPR technology, is make a small change in the genome so that the fetal hemoglobin continues to be produced or is reproduced, because the patients are older who are going to get this. Basically, what it’s doing is making a small change in the genome.
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The second one, called Lyfgenia, actually adds a functional beta-globin gene to the patient’s stem cells. It does the same thing in the end, where you’re going to make more fetal hemoglobin, but the Lyfgenia actually adds a beta-globin gene so that both of those are considered editing – one makes a change to the genome, and the second inserts a functional beta-globin gene because that’s what’s dysfunctional in sickle cell disease.
GB: Are these therapies a treatment for SCD or an actual cure?
MT: We say that these two therapies have curative potential. The reason that we put it that way is that it’s not necessarily an instant change in how the disease is expressed. But we certainly call it, as well, transformative.
What was seen in both clinical trials for these two therapies is people were in the trial if they had a number of vaso-occlusive pain episodes. The data that was presented at the American Society of Hematology was really pretty impressive in the sense that they were looking at complete resolution of the vaso-occlusive episodes after about six months. They saw that in 88% of patients who were in the study.
So, for 2,832 patients, they had a resolution of all of these pain episodes, and there were a lot. They were having a lot over the two years prior to when they got into the study. Once they got the Lyfgenia, there was a pretty impressive resolution to the vaso-occlusive episodes. That has the potential to really transform a person’s life because those episodes interrupt schooling, social activities — just everything. Every aspect of a person’s life.
GB: UCSF Benioff Oakland has been at the forefront of studying the CRISPR technology. Was it hard to get people to participate in the clinical trials? How important is Black participation in medical research and was it hard to get people to participate given historical mistrust of the medical system?
MT: People who are trusted by the person with sickle cell disease and their families are the best to explain these therapies. The sickle cell specialist should be explaining these therapies and assuring families that we are going to work in partnership with your transplant team to just make sure that you’re OK.
The reason why we don’t say it’s totally curative is [because] if a person has chronic kidney disease or chronic lung disease, those things aren’t necessarily going to get better. So that’s where we don’t say, “You’re completely cured,” because you may have had damage to your organs and bones and so on, and that definitely could continue after this treatment, so we work with the people who we treat and care for and really let them know that in the case of [our] sickle cell center, we have 50 years of having done trials, and really important trials like prophylactic penicillin.
People actually had to literally risk the life of their child in those studies to show that when you start penicillin at two months of age, then you’re going to stop the deaths in sickle cell that have been seen before and that are seen in other countries.
With that said, we’re able to explain that we’re here for you, we’re partnering with you, we’ve worked on other clinical trials over the years. We appreciate that the Black community has mistrust, but we actually are here to advocate, and make sure that you’re getting the proper monitoring and follow-up to make sure that things turn out in the best possible way. Given those partnerships, we were able to get people enrolled in those trials. The other thing that we’re doing is working really closely with sickle cell warriors to consider all of the challenges that people might face.
GB. When is the expected rollout?
MT. The rollout is already happening in terms of training. There’s something called qualified treatment centers, which we are one here at UCSF Benioff Children’s Hospital, in Oakland. The whole center has received specialized training to administer the complex gene therapy, and then further, it’s partnered with the comprehensive sickle cell center so that we have both the transplant or the gene therapy team and the sickle cell team has the expertise of genetic counseling, social work, and nurse practitioners. In the case of the sickle cell program, sickle cell specialists, community health workers, the manufacturer of Lfygenia established this network of qualified treatment centers that are all over the country.
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That’s what people should really look for – a qualified treatment center that’s partnered with a comprehensive sickle cell center so that they can get their personalized support so that everything can be explained to them about their particular situation: what they can expect, what’s going to be potentially transformed in relationship to the gene therapy, and what they may need to continue to have treatment on if they’re older and they have some other chronic condition.
GB: Cost of the treatments is a concern.
MT: That’s a huge issue. People have seen the press releases, and they see that one of the treatments has a price tag of $3 million. The second one has a price tag of $2 million. Dr. Walters, who is our [researcher] here at UCSF Benioff Children’s Hospital Oakland, is working in collaboration with UCLA and UC Berkeley on the CRISPR trial. And at UC Berkeley, there is a program called the Innovative Genomics Institute that is looking very carefully at how to bring the cost down, but also at how to make sure that the health care system and individuals aren’t burdened by these costs.
So, with Medicaid at the table, people certainly don’t have to be reassured that Medicaid will continue to pay people’s regular medical bills and for the hospital admission. The CRISPR technology, it is expensive. And again, at the Innovative Genomics Institute, they’re working together with Dr. Walters, myself, and sickle cell warriors to really think about how we can bring the cost down.
GB: Will the average sickle cell patient be able to afford this?
MT: There have been studies on the lifetime costs of living with sickle cell disease and the lifetime costs in terms of the interrupted employment and undereducation and underemployment. That price tag does balance out, but someone has to pay for the bill up front and then look to recoup that as the person lives a long and productive life and doesn’t have unexpected hospitalizations and so on from these vaso-occlusive episodes. The problem hasn’t been completely figured out, honestly, but there’s a lot of work to do.
Trials are still being conducted to improve sickle cell treatments. For more information, visit the UCSF Sickle Cell Center of Excellence’s website, sicklecell.ucsf.edu.
Editor’s note: For more on Dr. Marcia Treadwell’s work with sickle cell warriors, and that of local UCD physician Dr. Oyebimpe Adesina, see OBSERVER Senior Staff Writer Genoa Barrow’s in-depth series, “Painfully Aware: Understanding Sickle Cell and Its Impact on The African American Community.
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