2023 ended with an exciting biotech breakthrough for sickle cell patients. A gene-editing therapy using the revolutionary CRISPR technology provides new hope and options for the nearly 100,000 Americans with sickle cell disease. In this episode, we talk with the company behind one of the life-changing therapies, CASGEVY, and speak with two advocates for sickle cell patients.
2023 ended with an exciting biotech breakthrough for sickle cell patients. A gene-editing therapy using the revolutionary CRISPR technology provides new hope and options for the nearly 100,000 Americans with sickle cell disease. In this episode, we talk with the company behind one of the life-changing therapies, CASGEVY, and speak with two advocates for sickle cell patients.
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Theresa Brady (00:51):
Welcome to the first episode of our spring 2024 season. We start the season with an exciting biotech breakthrough. Sickle disease made headlines at the end of 2023 when the FDA approved the first treatments for the disease using the revolutionary CRISPR technology. This news provides hope to the nearly 100,000 Americans effected by sickle cell disease. Today, we talk with the company behind one of these life-changing therapies and we catch up with guests from a previous episode called Sickle Cell Saviors. We also discuss the racism and discrimination faced by too many sickle cell patients and we talk about how we can make resources more accessible to this community. I'm Theresa Brady and you're listening to I Am BIO.
(02:02):
Sickle cell disease is a common genetic disorder. It's caused by an inherited mutation in the gene for hemoglobin, the protein that carries oxygen through the body. This disease can have devastating consequences. Many people who have sickle cell disease experience symptoms like debilitating pain crises or failing organs. For some, it can even mean their life is cut short. For years, the most promising treatment was a bone marrow transplant. But, like most transplant procedures, a bone marrow transplant has barriers. Finding available donors, potentially life-threatening infections, the exorbitant cost, long hospital stays, and the risk of rejection.
(02:52):
The disease was neglected for decades. It wasn't until recently that more options became available, like Oxbryta. And with the approvals announced last year, patients may have more choices. Our first guest is from Vertex Pharmaceuticals, the company that developed the life-changing gene editing therapy, CASGEVY.
David Altshuler (03:17):
My name is David Altshuler and I'm the Chief Scientific Officer at Vertex Pharmaceuticals.
Theresa Brady (03:22):
David walks us through how CASGEVY was developed and the potential for sickle cell disease patients.
David Altshuler (03:29):
In 2015, Vertex and CRISPR formed a collaboration to develop a one-time gene editing treatment for sickle cell disease and beta thalassemia, as well as other diseases. Since then, we've worked together to discover, develop and now launch CASGEVY. CASGEVY is a one-time treatment for a potential lifetime of benefit. And the way it works is, it makes a change in the DNA of the cells, just of the blood cells, so that they express something called fetal globin. It's a type of hemoglobin that all of us have that's actually on when we're fetuses and in the first year of life and it can substitute for the mutant hemoglobin.
(04:14):
And the evidence from our clinical trials is that having CASGEVY treatment results in a dramatic reduction in the pain crises. In fact, over 90% of the people in our clinical trial had no pain crises after treatment with CASGEVY. And in addition, 100% of the patients had no hospitalization for pain crises after this time. So, it looks thus far to be a very effective medicine. CASGEVY was approved by the FDA in December of 2023 for people age 12 and above.
Theresa Brady (04:49):
People sometimes ask if CASGEVY is a cure.
David Altshuler (04:54):
We think of it as a one-time treatment with a potential for lifetime benefit. And I say that because while CASGEVY does address the underlying cause of the disease and the clinical data to date shows a dramatic reduction in vaso-occlusive crises, many people with sickle cell disease may already have organ damage because the disease led to a challenge for their kidney or their lung or some other tissue. And unfortunately, CASGEVY can't restore the function to an organ that was damaged. But the hope is that by addressing the underlying cause, the pain crises can be reduced or eliminated, the patient has improved quality of life. Or for patients who choose to have it earlier in life, hopefully that can reduce the amount of organ damage that they might suffer from.
Theresa Brady (05:38):
CASGEVY is promising. However, the patient must endure a lengthy and taxing process to undergo the treatment. David outlines the steps.
David Altshuler (05:48):
CASGEVY does involve a fairly significant experience for the patient and the doctors. The process involves three steps, each of which can take months. The first step is actually for the patient, to work with their doctor and their family and to decide if this is right for them. To learn about it, to undergo testing to see if they have all the different things checked that need to be checked, and to decide to proceed. The second step is to collect stem cells from their blood. They're shipped to a facility where they have the gene editing done. And then, the cells are checked for quality and that everything's ready. And then, they're shipped back to the doctor.
(06:30):
The third step is a bone marrow transplant. In order to benefit from the treatment, it's necessary to replace their existing blood cells with their own blood cells, except those that have this editing. And so, that involves a bone marrow transplant. They have to be treated with something called Busulfan, which is involved in chemotherapy. And that basically eliminates their existing blood cells. And then, they are given their own cells back with the edit. And they're in the hospital typically for four to six weeks to be monitored, to make sure that everything goes well, and if they need any supportive care to get the supportive care. And after four to six weeks, after their cells have engrafted, then they can go home and go on with their lives.
Theresa Brady (07:13):
As David explains, the CASGEVY procedure has less risk of rejection and benefits can last a lifetime.
David Altshuler (07:21):
One other thing about CASGEVY treatment, which is treating people with their own blood cells, what's called autologous bone marrow transplant, because they're receiving back their own cells, just with the genome edit is, there's no risk of rejection of those cells. Sometimes when people hear about a bone marrow transplant, they can also hear of those cells being rejected or what's called graft versus host disease. But actually, that can't happen with CASGEVY because it's not someone else's cells that might be rejected, it's actually your own cells that are the cells you had before, just with one precise and specific change to turn back on fetal globin so that the underlying cause and the symptoms of sickle cell disease no longer happen.
Theresa Brady (08:00):
Since the treatment is making changes to the DNA, we talk with David about whether these changes could be past from one generation to the next.
David Altshuler (08:09):
When people hear the letters DNA, they often think of inheritance, like parents passing along genes to children. But when we talk about CASGEVY editing the DNA, it's important to understand, this is only in the blood cells. So, there's no gene editing inside the body, because what's called ex vivo gene editing. The cells are taken out of the person with sickle cell disease, they're sent to a laboratory. The only cells that have gene editing are those blood stem cells that only give rise to white blood cells, red blood cells and platelets.
(08:44):
And then, when the cells are reintroduced in the body, there's no CRISPR left. So, there's no possibility of editing other cells. People often worry, and I think it's legitimate, about the concept of what's called germline gene editing, things that might be passed along to the children. That's not possible with CASGEVY, because the gene editing is only in these blood stem cells. And Vertex is not ever going to work on a germline gene editing. We are only working on people with serious life-threatening diseases and for whom there's no other treatment.
Theresa Brady (09:23):
The patient and caregiver voice is significant when developing new treatments and medicines. David tells us how Vertex put the patient first when developing CASGEVY.
David Altshuler (09:34):
In thinking about developing CASGEVY for patients with sickle cell disease, it has been really important and will remain very important that we work with the sickle cell community. This is a community that has been underserved over time and it's a community that for good reasons does not necessarily have the greatest faith in the medical system or in biotech or pharmaceutical companies. And so, from day one, we started to try and build relationship with people in the sickle cell community. Certainly it'll be incredibly important for us to continue to honor them and to work with them to figure out how this therapy can potentially be of benefit.
(10:18):
And we're really, I would say, proud of the fact that when this new technology of CRISPR came along, it has potential to help people with many diseases, we felt that sickle cell disease was among the group of patients who had the greatest unmet need, who might benefit the most from it. And that they shouldn't have to wait until others got in line in front of them and had the benefits. I trust we will continue to work with them and build on that relationship. It's critically important that we earn their trust and that we maintain that trust. And we take that very seriously at Vertex.
Theresa Brady (10:52):
Life is not easy for sickle cell patients and caregivers. Our next guest is a caregiver and advocate for sickle cell patients and someone you may know from our previous episode, Sickle Cell Saviors.
Mapillar Dahn (11:05):
My name is Mapillar Dahn and I am the Founder and CEO of the MTS Sickle Cell Foundation.
Theresa Brady (11:13):
Mapillar is the mother of three daughters. All three have sickle cell disease. She updates us on how they're doing.
Mapillar Dahn (11:21):
Tully, who is now getting ready to be 20, she is in college. She recently sadly had a hip replacement surgery, which led to a pulmonary embolism. So, we were all very scared for a while because she was in and out of the hospital. But, she has bounced back, as she usually does, and as most sickle cell patients usually do, because they're so resilient. She is ready to get back to school and just continue life. Deej, my middle daughter is 18. She's working. She's in school as well. Both of them go to the same school. I- I saw that coming, because they're so close (laughs).
(12:05):
She's still doing monthly blood transfusion. She had a stroke when she was in the second grade. Hajar, the baby, she's currently 14. She's in high school now. We found out a little over a year ago that she is high risk of stroke. So, she has went from being the least impacted by sickle cell disease to being majorly impacted because she has no recognitive issues from just not getting enough oxygen to her brain. And now she is at high risk of stroke, so she does monthly transfusions.
Theresa Brady (12:44):
According to a study published by Critical Care Nursing Quarterly in 2021, 50% of sickle cell patients waited at least two hours before treatment for their symptoms. Mapillar shares her experience about getting care for her daughters.
Mapillar Dahn (13:01):
The impact of dealing with a condition that is invisible just makes it so hard to get the help that a person or the caregivers may need, because oftentimes you're met with skepticism as to, "I know you say you're sick, but are you really sick? I don't, I don't see any (laughs) blood. You know? I don't see your arm in a sling." That's the most frustrating part, because that- that is essentially they're in an emergency room for hours in excruciating pain, but the level of emergency is not elevated to that of some other people who may come in.
(13:46):
But, this is someone who could have a stroke. This is someone who could have a heart attack. There's so many things that could be going on. But, because they're not hollering and screaming and you don't see blood, you minimize what they're going through. And even for caregivers, I mean, I have been fired from jobs because my kids were in the hospital and my employers were not sensitive to the fact that that's where I have to be.
Theresa Brady (14:14):
Unfortunately, stories like Mapillar's are all too common in the sickle cell community. Why aren't patients taken seriously? Why are their options so limited? Why aren't they getting the care they need? Our next guest is Ted Love, a medical doctor, biotech entrepreneur and an advocate for sickle cell patients.
(14:40):
After the break, Ted helps us explore these issues and what drove him to develop a breakthrough medication.
(14:58):
Do you have a question about biotech, but don't know who to ask? Ask us. In an upcoming episode of the I Am BIO podcast, our experts are standing by to inform, engage and educate you on what your curious about. Visit bio.org/podcast to submit your question about biotechnology. We hope to hear you on our podcast.
Ted Love (15:32):
I'm Ted Love. I'm Chairman of Bio and also former Chairman and CEO of Global Blood Therapeutics.
Theresa Brady (15:40):
Sickle cell disease effects millions of people around the world. However, in the United States, it mainly impacts people of color. For example, one in every 365 Black Americans is born with sickle cell disease. Ted explains why.
Ted Love (15:57):
Sickle cell disease is a genetic disorder which actually provides a survival advantage in areas of the world where malaria is very prevalent. And that's why it is more common in people who are descendants of areas where malaria was prevalent, like the Sub-Sahara Africa and, of course, Africans were imported to the United States. This is why African-Americans have more sickle cell disease.
Theresa Brady (16:26):
Although sickle cell is a common genetic disease, many patients, especially Black Americans are not getting the care they need. There are many reasons. Inadequate funding, lack of research, and limited access to healthcare. But what is at the root of it all?
Ted Love (16:44):
I first treated sickle cell patients when I was a medical student at Yale. And two things that struck me, one is that the poor options that we had for these patients compared to many other diseases. And also, the racism that these patients faced. A lot of skepticism about them pretending that they were sick and having pain in order to get access to pain medications. I've always said that sickle cell patients need more options and that was one of the most frustrating things to me when I was in medical training, the absolute dearth of options. I'll use cystic fibrosis as an example. When I was in medical school, CF was just as deadly as sickle cell disease. But at Yale, we had a special part of the hospital where those patients went. They got really optimized care.
(17:41):
And Yale was not unique. There were 100 such expert centers around the United States, because treating those patients was challenging and you wanted experts who knew how to provide the comprehensive care they needed. We don't have that for sickle cell. I- I think the neglect for innovation and science in sickle cell disease probably does relate to racism. I think it also relates to the belief that you could not make a good business if you were focused on sickle cell disease, which is why Global Blood Therapeutics, GBT was so important to me and why I came out of retirement. I wanted to prove that we could do both. We could make very innovative therapies to help these patients in a dramatic way, and we could build a valuable business while doing so.
Theresa Brady (18:30):
Improving access to treatment and resources is the first step to addressing the neglect of and discrimination against sickle cell patients. Ted shares how Pfizer's acquisition of GBT advances this goal.
Ted Love (18:44):
We think the sale of GBT to Pfizer benefited sickle cell patients in a number of ways. One way is that it really proved that you could build a valuable company (laughs) by focusing on sickle cell disease. So, the acquisition for $5.8 billion, uh, really did prove and in- in a clear way that our focus on sickle cell disease not only helped patients, but built value for investors. The only reason it was important is that sickle cell disease is a very common disease in many low resourced countries around the world. And GBT was working toward being a company which could make the therapy available at very low cost in those parts of the world, but Pfizer immediately has that capacity, given its, uh, much different financial position than a startup company.
Theresa Brady (19:37):
Making the treatment available and affordable is an exciting outcome of the Pfizer investment. Earlier, Ted talked about the treatment centers available for cystic fibrosis patients. He says, "We need similar solutions for sickle cell disease."
Ted Love (19:54):
This country needs to invest in doing that for sickle cell. And one of the things that I continue to work on is the passage of the Sickle Cell Treatment Act, so that we can fund approximately $535 million each year to establish these kind of centers around the country and also support many of the support groups, like the, uh, community-based organizations that need our support. But we need to also improve the treatment ecosystem around the country and that really is something that our federal government needs to step up and do.
Theresa Brady (20:31):
Vertex's David Altshuler also talks to us about what needs to be done to expand care for sickle cell disease.
David Altshuler (20:38):
I also think it's really critical that we improve the care for all patients with sickle cell disease in America. I think the patients who've been underserved and sometimes have not had access to the basic are they need. And one hope I have that might come from the attention to sickle cell that this CRISPR therapy has brought, because there has been a fair amount of attention to it, I hope it also leads to greater funding and support from the government and the healthcare systems for all patients, even those who can't yet benefit from CASGEVY or who choose not to, just improve the basic healthcare they have. So, we're happy to be spokespeople for that.
Theresa Brady (21:14):
As Ted and David said, it is important to expand awareness and resources for sickle cell patients and caregivers. That is something Mapillar is working on at the MTS Sickle Cell Foundation.
Mapillar Dahn (21:26):
So, the MTS Sickle Cell Foundation is a national organization that is dedicated to raising awareness, support and sensitivity surrounding sickle cell disease. This year, we are gearing up in April for a therapeutic summit. There needs to be a lot of education surrounding gene therapy and even some of the other therapies that have been approved. So, the therapeutic summit is going to help to educate the community about these different therapies that exist for sickle cell disease. We forged a partnership last year with the Georgia Public Library Service. It's an awareness initiative. There are over 400 public libraries in- in the state of Georgia. And through that partnership, we have sickle cell awareness, um, information in all of those branches throughout the state of Georgia.
(22:22):
We offer services like our temporary financial support service when resources allow. Through that initiative, we help pay rent, utilities, sadly, bereavement expenses. We have a scholarship initiative. Over the last two years, we've provided 20 scholarships to scholars who are impacted by sickle cell disease. Those are patients, siblings of sickle cell patients, children of sickle cell patients. We sent out care packages throughout the country to sickle cell patients. We do different things to be a source of support to families who are impacted by sickle cell.
Theresa Brady (23:10):
While the development of new treatments and medicines for sickle cell patients is a positive step, it's critical to recognize that there is still much work to be done to ensure a more hopeful future for those living with sickle cell disease. I want to thank our guests, David, Mapillar and Ted for helping us understand the treatment options for sickle cell disease patients and shedding light on the disparities in our healthcare system. And thank you for listening. I'm Theresa Brady and I produced this episode with help from Lynne Finnerty and Kourtney Gastinell. It was engineered and mixed by Jay Goodman, with theme music created by Luke Smith and Sam Brady. Make sure to subscribe, rate and/or review this podcast and follow us on X, formerly Twitter, Facebook and Instagram @iambiotech. And subscribe to Good Day BIO at BIO.org/goodday.