Potential for Cure with Gene Therapy and Final Thoughts

Key opinion leaders consider the possibility of cure for patients with sickle cell disease receiving gene therapy, and end the discussion by providing some closing thoughts. 

Biree Andemariam, MD: There was another assumption in my question about the cost of gene therapy compared with the evolving standard of care. The assumption was that gene therapy is potentially curative. Is it?

Julie Kanter, MD: We don’t know yet. I’m involved in quite a few trials, and I hesitate to use the word curative in any of them. What I tell patients very honestly is that I can guarantee they’ll be heavily disease modified if successful, but we won’t be able to determine cure. Then again, there are still some things about stem cell transplant. We know it’s a cure, because we know we biologically change the type of hemoglobin those individuals are producing, but we don’t completely know if it cures their organ dysfunction or if it completely cures some of the other adverse effects and complications of this disease. We have to look at it in those terms. We’re getting there. I don’t think we can quite say that. It’s important, and I tell patients all the time that all gene therapies are not created equal. One gene therapy is not the same as another, and we’re going have to figure out that there are going to be stopping rules. Some gene therapies shouldn’t continue, and there are going to be some that are better than others. We’re going to have make sure. I’m on the cure panel to create the way that we’re going to be able to analyze these gene therapies and compare them with one another, and I hope to compare them with stem cell transplant in a way that we can really understand the outcomes.

Biree Andemariam, MD: I want to thank all of you for this very informative discussion. But before we conclude, I’d like to get final thoughts from each of you. Michael?

Michael DeBaun, MD, MPH: I like Wally’s statement about utilitarian approach for this disease. At some level, we have to understand that the science that cures an individual with this disease is just as exciting as the science that informs a family about their risk of having a child with the disease so they can make an informed decision about whether they want a child with the disease. And that science is just as important as understanding environmental risk factors for mental health challenges that our families have. As we celebrate truly state-of-the-art science developed in the laboratory, I hope that we can start to celebrate, or at least have on the agenda, resources to better understand the social determinants of health in this population and to better understand ways to inform primarily a miseducated Black population in this country about their risk of having a child with sickle cell disease so that they can make informed decisions. Too often, I see a family whose newborn is 3 months old, and they say, “Nobody ever told me that I could have a child with sickle cell disease.” This happens in 2020, and there’s no effort by our leaders to address the lack of formal education and programs to better identify this.

Last, but not least, I’d like to comment on our burden as providers and leaders to understand the humanitarian requirement to expand the scope and research of sickle cell disease to the lower middle-income countries where 95% of the children with this disease are born and where pregnant women, in most of the countries in Africa, have a 10% rate of death. Nowhere in the world would that be tolerated, but on the continent of Africa, where pregnant women are associated with a 10% risk of death. I am excited about the basic science with curative therapy. I am cautious about expenditure of resources that don’t go to the greater good. That has to be a strategy where we learn to have all contingencies at the table when we talk about helping our families with sickle cell disease.

Biree Andemariam, MD: Thank you, Michael, for all those highlights that are deeply rooted in social justice. We really appreciate that. Julie, some last thoughts from you?

Julie Kanter, MD: It’s an exciting time to be a provider in sickle cell disease. We are finally getting to offer our patients options; something they’ve never had. Elliott said it really well earlier: Sickle cell disease sadly embodies the health inequities in our country. My goal is to really improve access to care, and I believe if we can do it here, then we can translate these findings to other places. But with a population that’s as small as ours is, compared with some of the larger populations of individuals with sickle cell disease, we’re not doing a good enough job. We have to figure out how to do our job better so that we can spread this other places. The science is exciting, and it is going to provide the pathway to improving access to care.

Biree Andemariam, MD: Thank you, Julie. Wally, some final thoughts?

Wally Smith, MD: Recently, I’ve been comparing our quest to climbing Mount Everest. We’ve got the backpacks and the Sherpas. We see the top of the mountain. We know what it means to go up there. We are nearing, perhaps, Base Camp 1. We’re picking up people and taking them with us to get to Base Camp 1. We need more people to come. After Base Camp 1, it’s going to get steeper and steeper, and we really have to begin with the end in mind and start the journey with enough resources, planning, and forethought to actually get to the top of Mount Everest.

Biree Andemariam, MD: I love the metaphor. Thank you, Wally. Elliott, take us home. What are your final thoughts?

Elliott Vichinsky, MD: I agree with what the other doctors said. You cannot stop science. There’s been an explosion of new therapies and understanding targets. These have the potential to benefit sickle cell significantly. That goes without question. So I support ongoing scientific trials. These drugs and therapies have real benefit.

What I’m troubled about is the historical, immoral approach to society about providing basic care prep for them. I have difficulty in focusing only on new therapies if the families don’t get the education, the mental health, and the basic standard of care that will allow them to make quality-of-life decisions. We can do better with developing an infrastructure for care. I don’t think we’re in that case, and I actually believe these drugs will pull the universities further into sickle cell care. In a lot of ways, it’s harder to get outpatient counseling and things done than it is to get on to a gene therapy trial right now. But just don’t forget where sickle cell was in the past. It was always a scientific disease that was great to study, but also remember what Michael said. We all remember what Linus Pauling, who made some incredible discoveries, did. He came out with a proposal that wasn’t thought out that trait carriers should have that tattooed across their foreheads so they would know that they were carriers.

I’m in favor of the science. It needs to be a partnership between the health care plan community and the scientists. We need an organization as we have for cancer in children. We need a real organization that works out multidrug trials. We need an organization that looks into the statistical and other variables that affect outcome and biomarkers. We need to approach this the same way we would cancer or leukemia. You would not do 1 drug at a time. You would have an organization that looked at that and correlated it. I’m excited that if we stick together, we’ll get there. Thank you.

Biree Andemariam, MD: Well, thank you. Thank you to all of you. I really appreciate your insights, and I’m sure our audience does as well. Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box.

Transcript Edited for Clarity