Motixafortide

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

_In vitro_ studies have shown motixafortide to have an IC₅₀ towards CXCR4 of 0.42 – 4.5 nM, with a binding affinity and dissociation rate that allows receptor occupancy to be maintained >72 hours. In healthy volunteers administered motixafortide monotherapy, CD34+ cell counts increased over time and reached maximal levels at 16 hours postdose. In the GENESIS study, motixafortide in combination with filgrastim mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures compared to filgrastim with placebo, while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs.

Motixafortide is an inhibitor of C-X-C Motif Chemokine Receptor 4 (CXCR4) that blocks the binding of its ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12). Both CXCR4 and SDF-1α play a role in the trafficking of hematopoietic stem cells to the bone marrow compartment, with CXCR4 helping to anchor stem cells to the marrow matrix (via SDF-1α or the induction of other adhesion molecules). The inhibition of CXCR4 thus results in elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation, facilitating their collection for the purposes of autologous transplantation.

Following subcutaneous injection, motixafortide Tmax ranged from 0.25 to 1.17 hours.

In animal studies in which radiolabeled motixafortide was administered, approximately 80% of the radioactive material was excreted in the urine. No parent drug was detected in the urine, and no single metabolite exceeded 30% of the total clearance.

In a typical patient, the estimated volume of distribution to the central compartment is 27 liters.

In a typical patient, the apparent total clearance of motixafortide is 46.5 L/h.