FDA Assigns Goal Date for Mavorixafor for Rare Immunodeficiency Disease


If approved, mavorixafor would be the first therapy for WHIM syndrome, an ultra-rare disease that can cause recurrent lung infections, papillomavirus-related warts, and an increased risk of developing certain types of cancer. The PDUFA date is April 30, 2024.

The FDA has accepted for priority review X4 Pharmaceuticals’ new drug application for mavorixafor to treat patients aged 12 and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024.

WHIM is an extremely rare immunodeficiency disease caused by reduced mobilization of white blood cells from the bone marrow due to oversignaling of the CXCR4/CXCL12 pathway. People with WHIM syndrome have very low blood levels of neutrophils and lymphocytes. About 60 cases have been reported in the medical literature, according to the Immune Deficiency Foundation.

Symptoms can vary but patients often experience recurrent infections with a high risk of lung disease, refractory warts from underlying human papillomavirus (HPV) infection, and an increased risk of developing certain types of cancer. Current treatment involves intravenous immunoglobulin or granulocyte colony-stimulating factor (G-CSF), an immune-cell-growth molecule. These treatments, however, do not specifically target the CXCR4 genetic defect,

Mavorixafor is an investigational small-molecule antagonist of CXCR4 being developed as a once-daily oral therapy.

The NDA is supported by the pivotal 4WHIM phase 3 clinical trial, which enrolled 31 patients. In the trial, mavorixafor treatment resulted in reductions in the rate, severity, and duration of infections in trial participants versus placebo. Mavorixafor was generally well tolerated, with no treatment-related serious adverse events reported and no discontinuations for safety events.

In May 2023, the company announced results of this trial, which showed that mavorixafor treatment results in about a 60% reduction in annualized infection rate, a greater than 75% reduction in the percentage of patients experiencing severe infections and a greater than 70% reduction in mean total days with infections.

These and additional 4WHIM phase 3 data were published in oral presentations at the annual meetings of both the Clinical Immunology Society and European Hematology Association.

X4 Pharmaceuticals continues research of mavorixafor in chronic neutropenic disorders, and is enrolling a phase 2 trial for people with idiopathic, cyclic, and congenital chronic neutropenia. A phase 3 trial is expected to begin in the first half of 2024 in certain chronic neutropenic disorders.

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