Mavorixafor: a CXCR4 antagonist for WHIM syndrome

WHIM syndrome is a rare primary immune deficiency and chronic neutropenia caused by overactivation of the C-X-C motif chemokine receptor 4/C-X-C motif chemokine ligand 12 (CXCR4/CXCL12) signaling pathway. On April 26th, 2024, Xolremdi (mavorixafor) capsules received its approval from US FDA, is the first targeted treatment specifically for patients aged ≥12 years with WHIM syndrome. Mavorixafor, as a selective CXCR4 antagonist, is able to increase the number of mature neutrophils and lymphocytes in the blood.

This review is to describe the pharmacological properties of mavorixafor and evaluate its clinical efficacy and safety profile.

A literature search was conducted using keywords mavorixafor, XOLREMDI, AMD070, AMD11070, X4P-001, WHIM Syndrome, and CXCR4/CXCL12 on Web of Science, Google Scholar, and PubMed. Drug information was obtained from the FDA website.

In the pivotal 52-week phase III trial, time above absolute neutrophil count threshold (TAT_ANC) values in the mavorixafor group were higher than those in the placebo group at 4 different time points (15.04 h vs 2.75 h; p < 0.0001), and mavorixafor group had lower infection frequency, severity and duration. The most common adverse events are thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.

Mavorixafor 400mg daily effectively increases WBC count, reduces disease symptoms and infection burden in WHIM syndrome patients ≥12 years. Future clinical programs will continue to evaluate the safety and efficacy of mavorixafor in patients with chronic neutropenic disease.