EBMT 2025 | The main benefits and challenges of gene therapy for sickle cell disease

Gene therapy has really opened up the doors for patients with sickle cell disease who did not have a matched donor available previously. Now, matched donors are available for less than 20% of patients. So one in five patients with sickle cell disease have a matched donor available. For the remaining four out of five, they didn’t have an option previously. Now alternative donor transplants have really improved, we are now using haploidentical transplants for patients with sickle cell disease and the outcomes are getting better, but with the use of an alternative donor, we have to really focus on the immune complications such as graft rejection, graft failure, graft versus host disease. These patients often need GvHD prophylaxis for an extended period of time between 6 to 12 months, which also involves frequent visits to the hospital for monitoring of the levels of the GvHD prophylaxis medications. So all this is very, very burdensome. 

In contrast, gene therapy is available to almost everybody because you don’t have to find a donor. You are your own donor. So that opens up the opportunity to many more patients to undergo gene therapy. And then again, once they’ve received the gene therapy product, the immune system is back to normal rather quickly in contrast to allogeneic transplantation. There is no need for any GvHD prophylaxis. These patients should technically not have graft rejection or GvHD. And so the post-infusion follow-up is relatively milder as compared to allogeneic transplantation, which is a huge advantage for many of these patients as well. 

So there are certainly these advantages, but gene therapy is very, very new. It’s complicated. It’s hard to explain. We have been doing transplants for sickle cell disease for almost 40 years now. Gene therapy has been around for less than 10 years. And so we don’t have the same degree of data to advise our patients about gene therapy. There are several thousands of patients who have received transplantation for sickle cell disease and other hemoglobinopathies. For gene therapy, I think there are maybe about between 100 and 200 patients worldwide who have received gene therapy, any kind of gene therapy. So there is a lot less data to counsel patients about the long-term effects, both short and long-term effects, of gene therapy. 

And then, of course, the big elephant in the room is the price tag. The two commercially available gene therapies, they are priced between $2 to $3 million. And I think insurance programs, payers everywhere are still trying to figure out how are we going to support these therapies? Once again, the clinical trials for gene therapy were only conducted in North America and Europe. Whereas if you look at the population density of sickle cell disease and thalassemia, these diseases are most prevalent in Africa, Southeast Asia, and South America. And none of these therapies are currently available in those parts of the world where the majority of patients with sickle cell disease and thalassemia live. So I think those are definitely challenges of access and equity that we have to figure out ways of making them more accessible. And in this regard, educational and academic institutions such as my own institution, St. Jude, and many other institutions around the world are developing low-cost methods of making these gene therapies accessible through partnership with other academic institutions and governments around the world.

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