ASH 2021 | GENESIS: Motixafortide prior to HCT in patients with MM
John DiPersio, MD, PhD, Washington University School of Medicine, Saint Louis, MO, presents results from the Phase III double blind GENESIS trial (NCT03246529) of motixafortide, a CXCR4 antagonist, as a mobilizing agent prior to autologous hematopoietic cell transplantation in patients with multiple myeloma. Patients received motixafortide once every two days as it was longer-acting in patients and when combined with granulocyte-colony stimulating factor (G-CSF), a statistically significant number of patients attained the number of CD34+ cells necessary for transplant. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
So the GENESIS trial is a trial designed to study a new drug and its easier name to pronounce is BL-8040, which is now Motixafortide, I think. And this is a CXCR4 inhibitor that is slightly different than Plerixafor. First of all, it’s slightly more active in preclinical models. Number two, it blocks for a much longer period of time. For instance, Plerixafor blocks very transiently and it’s washed off the receptor...
So the GENESIS trial is a trial designed to study a new drug and its easier name to pronounce is BL-8040, which is now Motixafortide, I think. And this is a CXCR4 inhibitor that is slightly different than Plerixafor. First of all, it’s slightly more active in preclinical models. Number two, it blocks for a much longer period of time. For instance, Plerixafor blocks very transiently and it’s washed off the receptor. So it has a very high off rate. BL-8040, this Motixafortide has a very long occupancy rate and a very slow off rate. So it actually continues to mobilize. And so you only need one dose every two days. So that’s a big benefit. So more active, longer acting. And the goal was to combine this CXCR4 inhibitor like we did with our previous studies with Plerixafor that was approved by the FDA in 2008, 2010. I can’t even remember, but the same concept. And we combined it with GCSF and randomized myeloma patients to receive either GCSF alone as a mobilizing agent or GCSF plus Motixafortide, which is BL-8040.
And the differences between the two groups were dramatic. This was a prospective double blind randomized trial, so it has all the trappings of a well-designed clinical trial. It was a two to one randomization to the combination of BL-8040 and GCSF versus the control group. And at one day of phoresis, approximately 90% of the patients reached the target of 6×10^6 CD34 per kilogram, versus only 9% in the control group. So a dramatic difference. And by two days, the difference was 92% to about 16%. So there was a huge difference between the two groups and that’s highly statistically significant. The drug was also very well tolerated, with only slight injection site reactions. And so now we have, for the first time, a second alternative CXCR4 inhibitor that actually, on paper, looks more active, has a lower off rate and a higher binding affinity to CXCR4, and when combined with GCSF dramatically synergizes the mobilization of stem cells in myeloma patients. And this trial will be a registration study, is a registration trial which will be used for FDA approval in the next few months.
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