X4 Pharmaceuticals Initiates Pivotal Phase 3 Clinical Trial of Mavorixafor for the Treatment of WHIM Syndrome
Global 4WHIM trial marks first-ever Phase 3 study in patients with WHIM syndrome
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
“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
Recently, X4 announced a partnership with
For more information on the 4WHIM Phase 3 trial (NCT 03995108), please visit www.clinicaltrials.gov.
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
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
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include statements regarding plans for, or progress, scope, cost, duration or results or timing for the initiation, completion or availability of results of development of mavorixafor (X4P-001) or any of our other product candidates or programs, including regarding the Phase 3 clinical trial of mavorixafor for the treatment of patients with WHIM syndrome, the Phase 2a portion of the Phase 1/2 clinical trial of mavorixafor in combination with axitinib in ccRCC, or plans to commence clinical trials of mavorixafor in SCN and WM, the target indication(s) for development, the size, design, population, location, conduct, objective, duration or endpoints of any clinical trial, or the timing for initiation or completion of or reporting of results from any clinical trial, the potential benefits of mavorixafor, or any other product candidate or program or the commercial opportunity in any target indication as well as the expected offerings and benefits of the PATH4WARD program and X4’s relationship with
2 McDermott, D and Murphy P, WHIM syndrome: Immunopathogenesis, treatment and cure strategies. Immunological Reviews. 2019;287: 91-102.
3 Arnolds K and Spencer J, CXCR4: A Virus’s Best Friend Infect Genet Evol. 2014 July 25 146-156.
4 Beaussant Cohen S, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry.
5 Badolato R, et al. How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. Blood. 2017 130: 2491-2498.
6 Boyle JM, Buckley,
7 Gathmann B, Grimbacher B, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006–2008. Clin Exp Immunol. 2009 Sep;157 Suppl 1:3-11.
8 Modell V, Gee B, et al. Global study of primary immunodeficiency diseases (PI) — diagnosis, treatment, and economic impact: an updated report from the
Westwicke, an ICR company
Westwicke, an ICR company