• 2 September 2020
    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

    X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, today announced the publication of comprehensive safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy data of mavorixafor from an ongoing Phase 2, open-label, dose-escalation and extension study in adult patients with genetically confirmed WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. The manuscript, published in Blood, the official journal of the American Society of Hematology, expands on previously presented data.

    Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals commented on the news: “The publication of our positive Phase 2 safety and efficacy data in a prestigious journal like Blood not only elevates the visibility of the severely underserved patient population suffering from WHIM syndrome, but also provides key third-party validation of our clinical strategy, including the selection of the dose, biomarkers, and clinical endpoints for our ongoing pivotal Phase 3 clinical trial. The published results continue to reinforce our belief that by down-regulating CXCR4/CXCL12 signaling, mavorixafor has the potential to be the first disease-modifying therapy for the more than 3,500 estimated diagnosed and undiagnosed WHIM patients in the U.S. We are eager to continue exploring mavorixafor’s compelling clinical profile and, if approved, bring this promising therapy to patients as expeditiously as possible.”

    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 David C. Dale, M.D., Professor of Medicine at the University of Washington School of Medicine, Seattle, WA, lead investigator of the Phase 2 and Phase 3 clinical trials, and an author of the publication. “With no approved therapies targeting the molecular mechanism of WHIM, I believe mavorixafor represents a promising new hope for WHIM patients.”

    The full Blood manuscript is available here: