X4 Pharma Reports Positive Top-Line Results from Pivotal Phase 3 Trial of Mavorixafor in WHIM Syndrome

X4 Pharmaceuticals reported positive top-line results from the global, pivotal 4WHIM phase 3 clinical trial of its lead investigational therapy, mavorixafor in people with WHIM syndrome.

Photo: Paula Ragan, president and CEO of X4

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 investigational small-molecule antagonist of CXCR4 being developed as a once-daily oral therapy to correct the dysfunction resulting from the underlying genetic causes of WHIM.

The 4WHIM phase 3 clinical trial was a global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of oral, once-daily mavorixafor in people with genetically confirmed WHIM syndrome. Originally designed to enroll 18-28 patients, the trial enrolled 31 patients aged 12 and older who received either 400 mg mavorixafor or placebo orally once daily for 52 weeks.

The study met its primary endpoint, with mavorixafor achieving clinical and statistical superiority over placebo when measuring TATANC, or the length of time that participants’ absolute neutrophil counts (ANC) remained above a clinically meaningful threshold of 500 cells per microliter (severe neutropenia), over 24-hour periods at 4 time points throughout the 52-week trial. Mean TATANC, was 15.04 hours in the treatment group versus 2.75 hours in the placebo group.

The study also met a key secondary endpoint, with mavorixafor achieving clinical and statistical superiority over placebo when measuring TATALC, or the length of time that participants’ absolute lymphocyte counts (ALC) remained above a clinically meaningful threshold of 1,000 cells per microliter (lymphopenia), over 24-hour periods at 4 time points throughout the 52-week trial. Mean TATALC was 15.80 hours in the treatment group versus 4.55 hours in the placebo group.

Increases in both TATANC and TATALC were maintained versus placebo and baseline across 52 weeks, demonstrating durability of treatment effect during the trial.

Mavorixafor was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events.

Following completion of the placebo-controlled portion of the trial, more than 90 percent of the eligible participants opted to receive treatment with mavorixafor in the open-label trial extension.

Additional data review and analysis of the secondary and exploratory endpoints of the 4WHIM trial are ongoing, with plans to present detailed results at a future medical meeting.

“These data not only give us strong confidence in the potential of mavorixafor to make a difference in the lives of those with WHIM syndrome and their families, but also strengthen our resolve to further evaluate mavorixafor in people living with chronic neutropenic disorders beyond those with WHIM,” said Paula Ragan, president and CEO of X4.

Based on these results, X4 Pharmaceuticals preparing to meet with U.S. regulatory authorities in the first half of 2023 to discuss next steps in advancing mavorixafor further towards a submission for regulatory approval and commercialization as the potential first treatment for people with WHIM syndrome.

For the WHIM indication, mavorixafor has been granted Breakthrough Therapy, Fast Track, and Rare Pediatric designations in the United States, and Orphan Drug Status in both the U.S. and European Union.

Author: Rare Daily Staff