RARE Daily

X4 Pharmaceuticals’ Phase 2 WHIM Treatment Data Published in the Journal Blood

September 2, 2020

Rare Daily Staff

X4 Pharmaceuticals said that comprehensive data from its mid-stage trial of mavorixafor for the treatment of adult patients with the rare genetic syndrome WHIM was published in Blood, the official journal of the American Society of Hematology.

“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.,” said Paula Ragan, president and CEO of X4 Pharmaceuticals.

WHIM syndrome is a rare, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. It is named for the characteristic clinical symptoms of the syndrome – warts, hypogammaglobulinemia, infections, and myelokathexis (reduction of circulating white blood cells). 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. The overall cancer risk in patients with WHIM is estimated to be 30 percent by 40 years of age. There are no approved therapies for WHIM.

Mavorixafor is a potential first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4, and is currently being investigated in a pivotal phase 3 global clinical trial for the treatment of WHIM syndrome.

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.

The phase 2 trial enrolled eight patients with a pathogenic CXCR4 mutation who were treated up to a maximum duration of 28.6 months with a median of 16.5 months, with five patients remaining on the extension study. The study established 400 mg once daily as a therapeutically effective dose, resulting in clinically meaningful increases in absolute neutrophil counts, absolute lymphocyte counts, reductions in infection rates, a 75 percent reduction in wart burden, and a safety profile showing that mavorixafor is well-tolerated.

The published report provides a detailed description of the pharmacodynamic response to mavorixafor, including patient-level data regarding the effect on neutrophils and lymphocytes. It also presents for the first time the effect of increasing doses of mavorixafor on total white blood cell counts and monocytes in this population. The manuscript also provides the most up-to-date long-term pharmacokinetic data, and 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.

Mavorixafor is currently being studied as a once-daily oral therapy in the phase 3 4WHIM trial, 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 anticipated to enroll up to 28 subjects in approximately 20 countries, followed by an open-label extension trial. Phase 3 results are expected in 2022.

“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 Dale, 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.”


Photo: Paula Ragan, president and CEO of X4 Pharmaceuticals



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