X4 Pharmaceuticals Announces Publication of Mavorixafor Phase 2 Clinical Data for Treatment of WHIM Syndrome in ‘Blood’ - the Official Journal of the American Society of Hematology
Manuscript further details positive clinical results and long-term tolerability of mavorixafor in ongoing Phase 2 study
Company continues to advance mavorixafor in Phase 3 pivotal trial in WHIM using optimal dose and key endpoints from Phase 2 trial
About the Phase 2 Trial. The Phase 2 clinical trial enrolled eight patients with a pathogenic CXCR4 mutation, an absolute neutrophil count (ANC) ≤400/μL and/or absolute lymphocyte count (ALC) ≤650/μL. Patients were given doses escalating from 50 mg up to 400 mg mavorixafor orally once daily based on the threshold-adjusted area under the curve for ANC and ALC over 24-hours (AUCANC and AUCALC). Primary objectives evaluated safety, tolerability, and the dose required to achieve a consistent increase in circulating neutrophils and lymphocytes. Exploratory objectives evaluated the efficacy of long-term mavorixafor treatment on infection rate, wart burden, white blood cells counts (WBCs), ANCs, ALCs, and absolute monocyte counts (AMCs). The Time Above Threshold for ANC (TATANC) was defined as the time, in hours, during which ANC was maintained above 500 cells/μL and TATALC as the time, in hours, during which ALC remained above 1,000 cells/μL. Patients were treated up to a maximum duration of 28.6 months with a median of 16.5 months; as of the date of publication, five patients remain on the extension study.
Key Results. In the study, mavorixafor 400 mg once daily was established as a therapeutically effective dose, demonstrating dose-dependent increases in patients’ WBCs, ANCs, ALCs, and AMCs. The 400 mg dose allowed the largest number of patients to increase their AUCANC and TATANC. Mavorixafor significantly reduced the annualized infection rate, with further reductions observed on extended treatment. Mavorixafor effected a 75% reduction in the number of cutaneous warts. To date, mavorixafor has been well tolerated.
What’s New in the Publication? The authors provide a detailed description of the pharmacodynamic response to mavorixafor, including patient-level data regarding the effect on neutrophils and lymphocytes. Also presented for the first time is the effect of increasing doses of mavorixafor on total white blood cell counts and monocytes in this population, adding to the understanding of the pleiotropic effect of mavorixafor on multiple cell types. In addition, the manuscript provides the most up-to-date long-term pharmacokinetic data, and, importantly, presents a detailed analysis of the clinical benefit of extended mavorixafor therapy on infections and warts, further substantiating its durable clinical efficacy compared to current therapeutic options for WHIM syndrome.
“Given these clinical data, the demonstrated therapeutic benefit of long-term mavorixafor treatment on infection rate and wart burden, and the favorable tolerability profile seen to date in this trial, we are optimistic that we will see similar results from the ongoing Phase 3 study of mavorixafor in patients with WHIM syndrome,” said
The full Blood manuscript is available here: https://bit.ly/2EZ82XW.
About Mavorixafor in WHIM Syndrome
WHIM is a rare, inherited, primary immunodeficiency disease caused by gain-of-function mutations in the chemokine receptor CXCR4, resulting in a reduced mobilization and trafficking of white blood cells from the bone marrow. The company estimates there to be more than 3,500 diagnosed and undiagnosed WHIM patients in the
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” or other similar terms or expressions that concern X4's expectations, strategy, plans or intentions. Forward-looking statements include, without limitation, statements regarding X4’s plans for clinical development of mavorixafor, including the timing of completion and results of its global Phase 3 clinical trial in patients with WHIM syndrome. Any forward-looking statements in this press release are based on management's current expectations and beliefs. Actual events or results may differ materially from those expressed or implied by any forward-looking statements contained herein, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in X4’s Quarterly Report on Form 10-Q filed with the
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Source: X4 Pharmaceuticals