EBMT 2025 | The status of gene therapy in sickle cell disease

Gene therapy for sickle cell disease has been in development for the last several decades, but fortunately, because of some developments in the field of human genetics where we have identified globin regulation much better now than we used to know before, identification of transcription factors such as BCL11A that are responsible for the globin switching and development of gene editing tools such as CRISPR-Cas9, we are now in a position to actually use all this information together to provide a genetic cure for patients with sickle cell disease. 

So as you probably know, there were two different genetic therapies that were approved in 2023. One which uses a lentiviral gene addition technique, it’s called lovo-cel, and the other technique which uses CRISPR-Cas9 and gene editing known as exa-cel. And both of these therapies have had remarkable results in the patients that have been treated on pivotal clinical trials. 

I think it’s safe to say that almost 90% of the patients have had either complete elimination of their painful vaso-occlusive crisis, or they’ve had significant reduction in the number of instances that these patients have to go to an emergency department or have a pain crisis, clearly showing the efficacy of these therapies. 

However, one thing that the entire medical community is sort of dealing with right now is these are very, very new therapies based on very novel gene editing platforms. And so we don’t really have long-term consequences, long-term outcomes of these patients. We follow these patients for maybe about three to five years. We don’t know what is going to happen to these patients in 15, 20, 25 years from now. So as we start treating more and more patients, especially younger patients, a number of these questions about… What sort of immune reconstitution will they have after gene therapy? What are the complications that they may or may not have after gene therapy? Is gene therapy truly a cure or is it more like a disease attenuation? Risk of leukemia, can patients develop leukemia after undergoing gene therapy for sickle cell disease? I think all of these questions are out there and they will be answered slowly as we gather more data on these patients who have received these therapies, so long-term follow-up is really essential, but it is an exciting time to be in the field because now we have so many different treatments for these patients which until a few years ago we did not.

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