Motixafortide: A New Drug to Mobilize Stem Cells Prior to Stem Cell Transplant

Many of us, myeloma patients, are familiar with the process to mobilize stem cells [also known as CD34+ cells] prior to harvest (and subsequent infusion after the receipt of melphalan). The harvesting process [apheresis] is tedious and, depending on the number of cells harvested can stretch over multiple days to yield an adequate number of cells needed for transplant. Some patients may never collect a sufficient number of stem cells for transplant. 

A presentation at the most recent ASH conference discussed the use and outcomes of the drug motixafortide as a novel option for stem cell mobilization. The quantity/dose of stem cells and progenitor cells is one of the most reliable clinical parameters to predict the quality of engraftment. The authors of the published abstract state, “A minimum HSPC dose of 2-2.5 million CD34+ cells/kg is considered necessary for reliable engraftment, while optimal doses of 5-6 million CD34+ cells/kg are associated with faster engraftment, as well as fewer transfusions, infections, and antibiotic days.” [Emphasis added]

Motixafortide is a member of a small class of drugs called selective inhibitors of the CXCR4 chemokine receptor. “CXCR4, is a well validated therapeutic target that is involved in the mobilization and trafficking of hematopoetic stem cells, immune cells and cancer cells from the bone marrow and the lymph nodes to the peripheral blood.” There is currently an FDA approved CXCR4 chemokine receptor antagonist already in clinical use in the US : the drug Mozobil (plerixafor) marketed by Sanofi-Aventis (and approved on December 15, 2008).

The ‘Standard of Care’ for stem cell mobilization is to inject patients with filgrastim (Granulocyte-Colony Stimulating Factor [G-CSF]) daily starting about 4 days prior to stem cell harvest. The developer of motixafortide (BiolineRx) has reported on the completed clinical study that compared a number of outcomes in two study arms with myeloma patients:

• Cohort 1 : was given the ‘traditional’ G-CSF injections PLUS a single dose of motixafortide
• Cohort 2 : was given the G-CSF injections plus a placebo

The results can be summarized as follows after ONE day of stem cell harvest:

• In Cohort 1 the harvest yielded a median of 10.8 million total cells/kg vs. only 2.3 million for cohort 2 (4.7x more).
• In addition, those patients dosed with the combination motixafortide + G-GCSF yielded:
  • 5.6x more stem cells;
  • 3.5x more multi-factor progenitor cells (MFP)
  • 5.6x more granulocyte macrophage progenitor cells (GMP)

These last two subgroups of cells add to the overall quality of the cell harvest.

• Eighty-nine percent of the patients in the motixafortide + G-CSF patients yielded more than enough stem cells needed to proceed to transplant after only one day of apheresis (compared to, typically, multiple days seen in current clinical practice). This is something that we would have appreciated when we went through the stem cell harvesting process (and that surely will be appreciated by future transplant patients).
• “Investigators also shared that the number of days needed for engraftment, success of engraftment, and the durability of engraftment at 100 days after transplant, all supported the novel combination.”
• “Additionally, infusion of higher numbers of [stem cells and  granulocyte macrophage progenitor cell] subsets was independently associated with faster [time to platelet engraftment], suggesting these more committed progenitors may play a critical role in early engraftment.” The faster engraftment will also not be lost on those of us who have gone through the stem cell transplant process as it speeds up the recovery from transplant and gets us back home faster too.

The BIG question you may have now is how motixafortide stacks up against the product currently used in clinical practice [Mozobil (plerixafor)]. We cannot yet make a direct comparison between the two agents because no ‘head-to-head’ clinical study has been completed yet. An indirect comparison, using the data generated for motixafortide, in the paper presented at ASH, referenced above, and the statistical analysis that was part of the FDA’s review process for plerixafor seems to indicate that the treatment effect of motixafortide is about 2x higher [see page 14] than that of Mozobil.

BiolineRx has indicated that they will file a New Drug Application (NDA) for motixafortide during the first half of 2022. If so, then there is a realistic chance that they may receive FDA approval towards the end of 2022 (assuming that their NDA file will meet all the stringent requirements demanded by US FDA).

Overall, this is good news for future patients in that this product will, hopefully, make life a little easier for those going through the stem cell transplant process. Many of us have ‘been there, done that’ and surely wish that things between the induction and consolidation phases of our myeloma journey would have gone faster and maybe with less knuckle-biting.