Motixafortide (Aphexda): uses, effects and side effects

Together with filgrastim, motixafortide helps collect a person’s own blood-forming stem cells before a stem cell transplant for multiple myeloma. The medicines move stem cells from bone marrow into the blood, where they can be collected and later returned to the same person. Because serious hypersensitivity reactions and other reactions can occur, premedication and medical monitoring are part of its use.

What is motixafortide?

Motixafortide is sold under the brand name Aphexda. It is a synthetic cyclic peptide—an artificially made molecule of amino acids connected in a ring. It blocks the CXCR4 receptor, helping collect enough of a person’s own blood-forming stem cells before transplantation for multiple myeloma. During development it was known as BL-8040 and BKT140. It was approved in the United States in 2023.

How does motixafortide work?

A signal in bone marrow keeps blood-forming stem cells there: the signaling molecule CXCL12, also called SDF-1, binds to CXCR4 receptors on their surface. Motixafortide also binds strongly to this receptor and blocks it for an extended period. It is therefore described as a long-acting CXCR4 antagonist. Blocking the receptor interrupts the retention signal, allowing stem cells to enter the blood. They can then be collected by apheresis, a procedure that separates selected components from blood.

Motixafortide is used with the growth factor filgrastim, which also mobilizes stem cells from bone marrow into the blood. The combination can increase the number of cells collected. An autologous transplant, in which a person receives their own stem cells, requires enough cells to be collected. Achieving this in fewer apheresis sessions reduces the collection burden.

In the phase 3 GENESIS trial, significantly more patients receiving motixafortide plus filgrastim reached the target collection amount within up to two apheresis sessions than those receiving filgrastim alone. The measured cells were CD34-positive: they carry a surface marker used to identify the collected stem cells. This result concerns stem cell collection before transplantation. 1

Is motixafortide FDA-approved?

Yes. The US Food and Drug Administration approved motixafortide in combination with filgrastim in 2023. The combination mobilizes stem cells for collection before autologous transplantation in people with multiple myeloma. Motixafortide is injected subcutaneously, meaning under the skin. Before the injection, patients receive medicines intended to reduce the risk of reactions. 2

What is motixafortide prescribed for?

Motixafortide is prescribed with filgrastim in preparation for autologous stem cell transplantation for multiple myeloma. The medicines move blood-forming stem cells from bone marrow into the bloodstream, where they can be collected. “Autologous” means that the stem cells come from the person receiving treatment. Before administration, the person receives an antihistamine and other premedication to reduce the risk of reactions.

What side effects can occur?

The US prescribing information [2] lists common side effects including:

• Injection-site pain, redness and itching
• Flushing, a sudden reddening of the skin with a feeling of warmth
• Back pain and nausea

More serious risks include:

• Severe hypersensitivity reactions or reactions affecting the whole body. Patients therefore receive premedication and are monitored during use.
• Possible mobilization of tumor cells: these too could move from bone marrow into the blood. For this reason, motixafortide is not used in leukemia.
• Possible harm to the embryo or fetus, termed embryo-fetal toxicity.