Mavorixafor: a CXCR4 antagonist for WHIM syndrome

Abstract

Background: 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.

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

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AMD070; Cxcr4/cxcl12; WHIM syndrome; XOLREMDI; mavorixafor.