X4 Pharmaceuticals Reports Positive Interim Data from Phase 2 Trial of Mavorixafor in Chronic Neutropenia and Starts Phase 3 Trial

X4 Pharmaceuticals, a company committed to improving the lives of individuals with rare immune system diseases, has reported promising clinical results from its Phase 2 trial of mavorixafor for treating chronic neutropenia (CN). This announcement highlights the drug’s safety and efficacy in increasing absolute neutrophil counts (ANC), a key measure for CN patients. Mavorixafor, an oral CXCR4 antagonist, has shown durability and tolerability as a monotherapy and when combined with stable doses of granulocyte colony-stimulating factor (G-CSF), the only U.S.-approved therapy for severe chronic neutropenia.

The Phase 2 study is an open-label, six-month trial involving 23 participants with idiopathic, congenital, or cyclic CN. The interim analysis, based on data up to May 14, 2024, focused on two groups: mavorixafor monotherapy and mavorixafor with stable-dose G-CSF, reflecting the participant population in the ongoing Phase 3 4WARD trial. Fifteen participants were part of these two groups; seven completed the study, and five continue to participate. Results from a third group receiving mavorixafor and dose-adjusted G-CSF are anticipated later this year.

Key findings from the interim analysis include that all evaluable participants who completed the six-month study achieved target ANC increases with once-daily mavorixafor, with or without stable-dose G-CSF. Participants on mavorixafor monotherapy reached mean ANC levels above the lower limit of normal for CN at three and six months. Additionally, mavorixafor monotherapy significantly increased ANC in participants with severe CN, maintaining mean ANC levels of approximately 800-1,000 cells/µL at various points during the study.

In combination with stable-dose G-CSF, mavorixafor led to increased mean ANC levels of over 1,000 cells/µL at months one, three, and six. Across all 23 participants, mavorixafor was generally well tolerated, with no serious drug-related adverse events reported. Three participants discontinued due to non-serious adverse events, consistent with previous studies.

Dr. Jean Donadieu, a pediatrician and coordinator of the French registry for chronic neutropenia, praised the findings, noting that they align with earlier Phase 1b results but now demonstrate a durable effect and good tolerability over six months. He emphasized the significance of these results for CN patients, who currently have limited treatment options.

X4 Pharmaceuticals has also initiated the Phase 3 4WARD trial, a global, pivotal study aiming to enroll 150 participants. This 52-week, randomized, double-blind, placebo-controlled, multicenter trial evaluates the efficacy, safety, and tolerability of once-daily mavorixafor, with or without G-CSF, in patients with congenital, acquired primary autoimmune, or idiopathic CN experiencing recurrent or serious infections. The trial's primary endpoint includes annualized infection rates and positive ANC responses.

Paula Ragan, Ph.D., President and CEO of X4 Pharmaceuticals, expressed optimism about the interim results, highlighting the potential of mavorixafor to significantly improve the lives of CN patients. She noted the momentum from mavorixafor’s first U.S. approval in April and the company’s commitment to advancing the 4WARD trial to provide another treatment option for patients in need.

Chronic neutropenia is a rare blood disorder characterized by persistently low neutrophil levels, leading to increased infection risk and reduced quality of life. Mavorixafor works by downregulating the CXCR4 receptor, mobilizing neutrophils from the bone marrow into the bloodstream, which has shown effectiveness across various diseases.

X4’s ongoing efforts in clinical trials aim to establish mavorixafor as a viable oral treatment option for chronic neutropenia, providing a significant advancement for patients who currently rely on injectable therapies with notable side effects.