General Information

Aphexda is a hematopoietic stem cell mobilizer.

Aphexda is specifically indicated for use 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 is supplied as an injection for subcutaneous use.

Dosing/Administration:

Premedicate all patients before each dose of Aphexda to reduce the risk of hypersensitivity and injection site reactions.

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.

Mechanism of Action

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 of 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.

Clinical Trial Results

The FDA approval of Aphexda was based on results from the 2-part, Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Aphexda (motixafortide) plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.

The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. Aphexda plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of ≥ 6 × 106 CD34+ cells/kg within two apheresis sessions, versus 9.5% for the placebo plus filgrastim regimen, as measured by central laboratory. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the Aphexda arm and 21.4% in the placebo arm, as measured by local laboratories.