• 26 June 2019
    X4 Pharmaceuticals Initiates Pivotal Phase 3 Clinical Trial of Mavorixafor for the Treatment of WHIM Syndrome

    X4 Pharmaceuticals, Inc. (Nasdaq:XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, today announced the initiation of 4WHIM, a pivotal Phase 3 global clinical trial of mavorixafor (X4P-001) for the treatment of WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, inherited, primary immunodeficiency disease.

    The global 4WHIM trial is a 52-week, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of mavorixafor in genetically confirmed WHIM patients. The trial is designed to enroll up to 28 subjects in approximately 20 countries, followed by an open-label extension trial.

    The primary efficacy endpoint for the trial will compare the level of circulating neutrophils relative to a clinically meaningful threshold (500 cells/µL), in response to mavorixafor versus placebo measured during multiple 24-hour periods over the course of 52 weeks. Secondary endpoints include infection rates, wart burden, and assessments of immune system function and quality of life.

    Mavorixafor is a potentially first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4. Proof of concept in WHIM patients has been demonstrated with meaningful increases in neutrophil and lymphocyte counts, both important biomarkers of CXCR4 signaling and immune function. Mavorixafor has been well tolerated in prior early phase clinical studies.

    “We are very excited to initiate our global Phase 3 4WHIM trial as we seek to confirm mavorixafor’s transformative potential as a novel therapy for patients with WHIM,” said Lynne Kelley, M.D., FACS, Chief Medical Officer of X4 Pharmaceuticals. “Despite the severity of the disease and its significant burden on patients’ long-term health and daily quality of life, WHIM is often overlooked and misdiagnosed. As the first-ever late-stage clinical trial for the treatment of WHIM syndrome, initiation of this study is a critical step in bringing a new treatment option to this underserved patient population.”

    “This marks an important milestone for X4 as we advance our lead drug candidate into the company’s first pivotal Phase 3 clinical trial,” commented Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “Following on the success of our Phase 2 clinical trial, we are excited to build on our progress and commitment to innovate for patients throughout the world suffering from rare diseases such as WHIM.”

    Recently, X4 announced a partnership with Invitae Corporation to support confirmation of a WHIM diagnosis, among other inherited primary immunodeficiencies. Through the collaborative PATH4WARD program, X4 and Invitae will provide genetic testing at no charge to patients to help clinicians expedite the diagnosis of these disorders.

    For more information on the 4WHIM Phase 3 trial (NCT 03995108), please visit

    About WHIM Syndrome

    WHIM syndrome is a rare, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene and is named for the characteristic clinical symptoms of the syndrome – Warts, Hypogammaglobulinemia, Infections, and Myelokathexis.1 Patients with WHIM may experience significant morbidity beginning in early childhood and continuing throughout life with an increased likelihood of various recurrent, potentially life-threatening infections, and may also be susceptible to malignancies such as HPV-related cervical cancer and lymphomas.1,2,3 The overall cancer risk in patients with WHIM is estimated to be 30 percent by 40 years of age.4 There are no approved therapies for WHIM, and current standards of care are limited to treatment of acute infections with antibiotics or prevention of infections mainly through immunoglobulin substitution or G-CSF.5 The exact prevalence of WHIM is unknown, however, in the U.S. alone there are between 15,000 and 100,000 patients classified as having a primary immunodeficiency disease of unknown origin – of which WHIM is one.6,7,8

    About Mavorixafor

    X4 Pharmaceutical’s lead product candidate, mavorixafor (X4P-001), is a potentially first-in-class, once-daily, oral inhibitor of CXCR4, currently in Phase 3 development for the treatment of WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. Mavorixafor has demonstrated proof of concept in WHIM in a Phase 2 trial, including clinically meaningful increases in neutrophil and lymphocyte biomarker counts, as well as a trend of reduction in infection rates and wart burden, and a favorable safety profile. Mavorixafor was designated orphan drug status by the U.S. Food and Drug Administration in 2018 for the treatment of WHIM and is also in development for Severe Congenital Neutropenia (SCN), Waldenström’s macroglobulinemia (WM), and clear cell renal cell carcinoma (ccRCC).