RARE Daily

X4 Pharmaceuticals Reports Positive Phase 3 Results for Mavorixafor in Patients with WHIM Syndrome

May 17, 2023

Rare Daily Staff

X4 Pharmaceuticals highlighted new data from its global, pivotal, 4WHIM phase 3 clinical trial of once-daily, oral mavorixafor in individuals with WHIM syndrome that focuses on the impact of mavorixafor on the rate, severity, and duration of infections in trial participants.

Highlights included a 60 percent reduction in annualized infection rate seen in the mavorixafor arm vs. placebo; greater than 75 percent reduction in the percentage of individuals experiencing severe infections in the mavorixafor group vs. placebo group; and greater than 70 percent reduction in mean total days with infections (2 weeks on mavorixafor treatment vs. 7 weeks on placebo.

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare, inherited, combined immunodeficiency disease caused by reduced mobilization and trafficking of white blood cells from the bone marrow due to over-signaling of the CXCR4/CXCL12 pathway. People with WHIM syndrome characteristically have very low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience frequent, recurrent infections with a high risk of lung disease, refractory warts from underlying human papillomavirus (HPV) infection, limited antibody production due to low levels of immunoglobulin, and an increased risk of developing certain types of cancer.

Mavorixafor is an experimental small-molecule antagonist of CXCR4 being developed as a once-daily oral therapy to correct the dysfunction resulting from the underlying causes of WHIM. For the WHIM indication, mavorixafor has been granted Breakthrough Therapy, Fast Track, and Rare Pediatric designations in the U.S., and Orphan Drug Status in both the U.S. and European Union. Should mavorixafor be approved in the U.S. for the indication of WHIM syndrome, X4 could be eligible to receive a Priority Review Voucher (PRV).

“Today, we’re announcing that mavorixafor treatment demonstrated statistically significant and clinically meaningful improvements across a number of key infection metrics versus placebo in our pivotal, phase 3 trial in those diagnosed with WHIM Syndrome,” said Paula Ragan, president and CEO of X4 Pharmaceuticals. “Given that frequent, severe, and long-lasting infections remain the most challenging burden for individuals with WHIM syndrome, we believe that demonstration of these clinical benefits in the 4WHIM trial are an important step in delivering a much-needed breakthrough for patients and their caregivers.”

The data will be presented at the upcoming annual meetings of the Clinical Immunology Society and the European Hematology Association. X4 Pharma recently completed a pre-NDA meeting with the FDA and remains on track to submit for U.S. approval of mavorixafor for WHIM syndrome early in the second half of 2023.

Based on the results from the 4WHIM trial, X4 also plans to advance mavorixafor as a potential treatment for the estimated 50,000 patients in the United States diagnosed with idiopathic, cyclic, and congenital chronic neutropenia.

Photo: Paula Ragan, president and CEO of X4 Pharmaceuticals

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