ASH 2025 | First promising results of exa-cel in pediatric patients with TDT or SCD and recurrent severe VOCs

So, we are very grateful for ASH for allowing us to present the data for the exa-cel study. This is the first data on patients who are 5 to 11 years of age, and we presented data on 11 subjects with sickle cell disease and 13 subjects with the transfusion-dependent beta thalassemia, who are between the ages of 5 and 11. The inclusion criteria for both pediatric studies was similar to what we have reported in the pivotal trial. Basically, transfusion-dependent beta thalassemia patients needed to have a transfusion regimen of at least 100 mL per kilogram per year in the last two years prior to enrollment. And for those with sickle cell disease, they needed to have a minimum of two vaso-occlusive crises per year in the last two years. And what we have seen is actually that the collections, those pediatric patients collected much better in less cycles than what we have seen in our adult patients, but very similar to what we have seen in our adolescent cohort, up to 18 years of age. And every patient collected with three or less mobilization cycles. 

Now, when you look at the results, if you look at the transfusion-dependent beta thalassemia, every single patient stopped transfusions at a median of around one, one and a half months. And if you look at the six patients that had enough follow-up, meaning at 12 consecutive months of follow-up after the last red blood cell transfusion, 100% of the patients met our primary endpoint of being transfusion-independent with a normal hemoglobin adjusted for age, which is quite encouraging because what we see is that the patients responded extremely well to this therapy. Similarly, in those with sickle cell disease, none of the patients after therapy developed any vaso-occlusive crises. And for those patients that had long enough follow-up, again, 100% of the patients met our primary endpoint, which is being free of vaso-occlusive crises for a year, or being hospital-free from admissions, which was our secondary endpoint. And again, all these patients achieved a hemoglobin, which is normal, adjusted for age, and a minimum fetal hemoglobin of 40%. 

So again, if you look at our data in the adult, then the adolescent, then the pediatric data, this data clearly shows that individuals treated at a younger age in this situation, 5 to 11 years of age, did very well. And this is what you expect because you are actually treating before you start any potential side effects, correct? So a lot of individuals with sickle cell and beta thalassemia have irreversible damage from their disease as they grow older. And treating them early before these complications happen actually speaks very well to the fact that they respond very well by the fact that we had 100% response in TDT and 100% response in sickle cell disease. 

The safety profile was consistent with what you expect with high-dose chemotherapy with busulfan and autologous transplant. Two of the individuals with transfusion-dependent beta-thalassemia developed a complication called veno-occlusive disease of the liver, and unfortunately, one of them passed away related to that complication, which has been reported as a side effect of potential busulfan chemotherapy. The rates of VOD in the TDT patients are very similar to what people have reported in individuals undergoing allogeneic transplant for TDT. So our results are very encouraging. And again, it solidifies the idea that treating early is potentially better for patients than treating later after you develop side effects.

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