X4 Pharmaceuticals Reports Positive Phase 2 Trial Results for Mavorixafor in CN

X4 Pharmaceuticals, a company focused on enhancing the lives of individuals with rare immune system diseases, has reported promising results from its completed Phase 2 clinical trial of mavorixafor, an oral CXCR4 antagonist, for treating chronic neutropenia (CN). The six-month study demonstrated that daily oral mavorixafor significantly elevated the mean absolute neutrophil counts (ANC) of participants. Furthermore, when used in conjunction with injectable granulocyte colony-stimulating factor (G-CSF), mavorixafor allowed for substantial reductions in G-CSF dosage while maintaining normal ANC levels.

Dr. Teresa Tarrant from Duke University School of Medicine highlighted the unmet need for an optimal long-term treatment for severe chronic neutropenia, stating that the Phase 2 results are encouraging. The results showed not only an increase in circulating neutrophils but also confirmed their functionality in a sub-study population. She looks forward to the larger Phase 3 mavorixafor CN trial, expressing optimism about its potential to provide a much-needed treatment innovation.

Paula Ragan, Ph.D., President and CEO of X4 Pharmaceuticals, expressed satisfaction with the six-month Phase 2 study results, which align with previous findings of mavorixafor significantly increasing ANC in the CN population. These results offer insights into the potential real-world application of mavorixafor, pending approval, and bolster confidence in the success of the ongoing Phase 3 4WARD trial.

The Phase 2 study involved 23 participants with idiopathic, congenital, or cyclic chronic neutropenia, divided into two treatment groups: mavorixafor monotherapy and mavorixafor combined with G-CSF. Results from the monotherapy group showed a durable increase in mean ANC, reaching normal levels by the third and sixth months. Participants with severe CN saw more than a two-fold increase in mean ANC levels over six months. In the combination group, physicians reduced G-CSF dosing for nine of twelve eligible participants, with mean reductions of 52% at three months and 70% at six months, all while maintaining normal ANC levels.

A sub-study comparing the functionality of neutrophils in CN participants to healthy donors found that the mean percentage of functional neutrophils in CN participants was comparable to that of healthy donors after six months of mavorixafor treatment. This marks the first clinical demonstration of the functionality of neutrophils mobilized by mavorixafor, reinforcing the company’s confidence in the Phase 3 4WARD trial.

Chronic neutropenia is a rare blood disorder characterized by an increased risk of infections and a reduced quality of life due to low neutrophil levels. Neutrophils are typically retained in the bone marrow by the CXCR4/CXCL12 axis. Mavorixafor, an orally active CXCR4 antagonist, mobilizes neutrophils from the bone marrow into the blood, as demonstrated across multiple disease states.

The Phase 1b/Phase 2 clinical trial evaluated oral mavorixafor with or without G-CSF in participants with chronic neutropenia. The initial Phase 1b study showed a 100% response rate to mavorixafor, with favorable tolerability. The Phase 2 portion assessed the safety and impact of daily mavorixafor over six months.

The ongoing Phase 3 4WARD trial is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of oral mavorixafor (with or without G-CSF) in individuals with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia experiencing recurrent infections. Aiming to enroll 150 participants, the trial’s primary endpoint is based on annualized infection rate and positive ANC response.

X4 Pharmaceuticals is advancing patient care by developing innovative therapies for rare immune system diseases, leveraging their expertise in CXCR4 and immune system biology. Mavorixafor has received U.S. approval as XOLREMDI® capsules, and its potential use in additional indications is being explored.