X4 Pharmaceuticals announced that the United States Food and Drug Administration (FDA) has accepted for filing the company's New Drug Application (NDA) for once-daily, oral mavorixafor to treat individuals aged 12 and older with WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, primary immunodeficiency. The FDA granted Priority Review of the mavorixafor NDA, establishing a goal of six months review from the date of acceptance and assigning a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024. The FDA's acceptance of mavorixa for NDA with priority review represents yet another significant step forward towards a potential treatment for those with WHIM syndrome, a rare disease for which there are currently no approved therapies.

Mavorixafor is an investigational small-molecule antagonist of the CXCR4 receptor being developed as a once-daily oral therapy for WHIM syndrome and certain chronic neutropenic disorders. For the WHIM syndrome indication, mavorixafor has been granted Breakthrough Therapy Designation, Fast Track Designation, and Rare Pediatric Disease (RPD) Designation in the U.S., and Orphan Drug Status in both the U.S. and European Union. Upon FDA approval of a product with RPD designation, the sponsor can receive a Priority Review Voucher that can be used to obtain priority review for a subsequent application or sold to another drug sponsor.

The NDA is supported by the results of the global, pivotal, 4WHIM Phase 3 clinical trial of once-daily, oral m flavorixafor in individuals with WHIM syndrome. The 4WHIM trial met its primary endpoint of time above threshold for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001), a key secondary endpoint, and was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events.

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. An open-label extension phase of the clinical trial is ongoing (NCT03995108). Following successful completion of a global, pivotal, Phase 3 clinical trial, the company are seeking U.S. approval of oral, once-daily Mavorixafor for the treatment of people aged 12 years and older with WHIM syndrome.

The company also currently planning a Phase 3 clinical program evaluating mavorixafor in certain chronic neutropenic disorders".