ASH 2025 | Fixed-dose vs weight-based plerixafor in patients with SCD receiving BEAM-101 in the BEACON trial

Yeah, in the BEACON analysis, we talked about our mobilization strategy using a fixed-dose plerixafor of 20 milligrams for individuals less than 83 kilograms versus per kilo dosing, which is what has been used in other gene therapy trials of 0.24 milligram per kilogram. And this was limited to individuals with sickle cell disease. And there were 31 patients that were infused with the BEAM-101 product. 

So what we did is we did pharmacokinetic modeling, and we have shown that giving a fixed dose of plerixafor of 20 milligrams can potentially increase the plerixafor AUC for those who are less than 83 kilograms. And the exposure was very stark for the patients who weighed less than 83, and it was very similar to what you expect in individuals who are 83 kilograms or larger. And what we have done is the protocol was amended in September of 2024 to give fixed dosing to everybody that weighs less than 83 kilograms. And if you look at our data that we presented at ASH, those who received fixed dosing mobilized better in less cycles of mobilization, which was actually very encouraging. And more importantly, we were able to collect patients for four consecutive days, which is quite novel in the gene therapy world, because most gene therapy products in the past have mobilized patients and collected them over two or potentially three days. But for the first time, we reported that collecting cells over four days is not only feasible, it’s also safe for patients with sickle cell disease. They tolerated it very well. And those receiving higher dose plerixafor at a fixed dosing of 20 milligrams mobilized better and more efficiently. And their CD34 count prior to mobilization was higher, and the yield in the stem cells was higher. 

Now, also, I reported in the same presentation on the engraftment in the BEACON trial, and what we have shown is a robust early engraftment of neutrophil and platelets, and the median times was less than 20 days for the neutrophils. And what we also have shown is that a third of the patients that received this therapy did not require platelet transfusion, which is also quite impressive, knowing that most gene therapy patients will require multiple transfusions after busulfan chemotherapy. And we also reported on the efficacy, although it is early and we continue to follow these patients. And none of the patients developed any VOCs that are reported by the principal investigators for these individuals over the period of the follow-up that we have shown. 

And one important point that we also talked about is because the BEAM-101 is manufactured in-house, there is in-house manufacturing, and it is a closed efficient system. The products were released much faster than what we have seen in other gene therapy trials. The median time to release the product was 2.9 months, which is around three months from the time you finish the collection to the product being ready to be shipped. 

So these results are very encouraging. Again, using a fixed dose plerixafor at 20 milligrams fixed dosing for those weighing less than 83 kilograms showed great promise with less cycles of mobilization and better stem cell yield, allowing patients to undergo less mobilization cycles and thus decreasing the journey for patients and decreasing the potential side effects of multiple collections. We also reported on the safety after infusion of the product, and the safety is very comparable with what we expect with busulfan chemotherapy and autologous transplant. And we unfortunately reported that one patient, which we talked about before in prior meetings, passed away secondary to an idiopathic pneumonia syndrome related to busulfan and not related to the product. So these are very encouraging early data and very robust data in mobilization for individuals with sickle cell disease.

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