Motixafortide

APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. APHEXDA, a hematopoietic stem cell mobilizer, is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

Motixafortide is an inhibitor of the C-X-C Motif Chemokine Receptor 4 (CXCR4) and blocks the binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12). SDF-1α and CXCR4 play a role in the trafficking and homing on human hematopoietic stem cells to the marrow compartment. Once in the marrow, stem cell CXCR4 can help anchor these cells to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules. Treatment with motixafortide resulted in leukocytosis, and elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation in mice, rats, dogs, and humans. Stem cells mobilized by motixafortide were capable of engraftment with long-term repopulating capacity in a rodent transplantation model.

2 DOSING AND ADMINISTRATION Initiate APHEXDA treatment after filgrastim has been administered daily for 4 days. Recommended dosage is 1.25 mg/kg actual body weight by subcutaneous injection 10 to 14 hours prior to initiation of apheresis. A second dose of APHEXDA can be administered 10 to 14 hours prior to a third apheresis. See Full Prescribing Information for instructions on preparation and administration.

APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide. History of serious hypersensitivity to APHEXDA.

Anaphylactic Shock and Hypersensitivity Reactions: Premedicate all patients with a combination of an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor prior to each APHEXDA dose. Administer APHEXDA in a setting where personnel and therapies are available for immediate treatment. Observe for signs and symptoms and manage promptly. Injection Site Reactions: The addition of analgesic premedication (e.g., acetaminophen) is recommended. Tumor Cell Mobilization in Patients with Leukemia: APHEXDA may mobilize leukemic cells and should not be used in leukemia patients. Leukocytosis: Increased circulating leukocytes have been observed. Monitor white blood cell counts during APHEXDA use. Potential for Tumor Cell Mobilization: Tumor cells may be released from marrow during HSC mobilization with APHEXDA and filgrastim. Effect of reinfusion of tumor cells is unknown.

The following clinically significant adverse reactions are discussed in other sections of the labeling: Anaphylactic Shock and Hypersensitivity Reactions Injection Site Reactions Potential for Tumor Cell Mobilization in Patients in Leukemia Leukocytosis Potential for Tumor Cell Mobilization Most common adverse reactions (incidence >20%) are injection site reactions, injection site pain, injection site erythema, injection site pruritus, pruritus, flushing, and back pain.

Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Discard prepared reconstituted solution after 24 hours storage under refrigeration 2°C to 8°C (36°F to 46°F) or at room temperature 20°C to 25°C (68°F to 77°F) protected from light.