FDA Grants Fast Track Designation to Mavorixafor for Chronic Neutropenia

The US Food and Drug Administration (FDA) has granted Fast Track designation to mavorixafor, an oral CXCR4 antagonist, for the treatment of chronic neutropenia (CN).

Announced by X4 Pharmaceuticals on 10 June 2025, the agent is currently being examined in an ongoing phase 3 study called the 4WARD trial.1

“We are thrilled that the FDA has recognized the unmet needs in the chronic neutropenia community and granted us Fast Track designation for mavorixafor for the treatment of CN,” said Christophe Arbert-Engels, MD, PhD, Chief Medical Officer of X4 Pharmaceuticals. “We look forward to working with the FDA and leveraging the benefits of the designation, which include more frequent communication with the agency and the potential for accelerated approval and/or priority review if certain criteria are met and maintained.”1

Mavorixafor was previously approved in 2024 for the treatment of WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) in patients ≥12 years. According to X4 Pharmaceuticals, the treatment is the first specifically indicated in patients with WHIM syndrome and was granted Breakthrough Therapy Designation prior to its application approval in September 2023.2

Chronic neutropenia, a rare blood disease, is characterized by low levels of circulating neutrophils, which increases risk of infections and reduces quality of life. Neutrophils are typically contained in bone marrow by the CXCR4/CXCL12 axis, which create a reserve of cells. Mavorixafor downregulates the CXCR4 receptor, which has been shown to mobilize functional neutrophils from the bone marrow into the peripheral blood.1

Currently, the only FDA-approved treatment for CN is a human recombinant granulocyte-colony stimulating factor (G-CSF), delivered intravenously. G-CSF is known to cause several side effects, including splenomegaly, thrombocytopenia, glomerulonephritis, vasculitis, osteoporosis, and bone pain. Long-term treatment is also associated with increased risk of leukemia in patients with congenital neutropenia, particularly at high doses.1

Because of these often dose-limiting toxicities, patients do not usually receive the optimal dosage recommendation. To that end, X4 Pharmaceuticals believes that mavorixafor has the potential to benefit those with certain primary CN conditions.1

In 2024, X4 Pharmaceuticals announced positive results from a 6-month phase 2 trial of mavorixafor in CN, which displayed durable and meaningful elevations in patients’ mean absolute neutrophil counts (ANC). Additionally, it allowed for substantial reductions in G-CSF dosing while maintaining ANC. The trial itself was an open-label clinical trial enrolling 23 patients diagnosed with idiopathic, congenital, or cyclic chronic neutropenia. Patients were split into two cohorts: one received mavorixafor, and the other received a combination with G-CSF treatment. In the latter cohort, 9 of 12 had their G-CSF dosing reduced; 8 had it reduced at the earliest possible time point, and 3 were taken off treatment altogether.3

X4 Pharmaceuticals is currently conducting a global phase 3 clinical trial, 4WARD, evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor, with or without injectable G-CSF. Specifically examining patients with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections, the study aims to enroll 150 participants with confirmed trough ANC levels <1000 cells/microliter at baseline and histories of ≥2 serious and/or recurrent infections in the year before.1

4WARD is a randomized, double-blind, placebo-controlled, multicenter study that will last 52 weeks. Its primary endpoint is based on 2 separate outcome measures: annualized infection rate and positive ANC response.1

“With enrollment ongoing in our phase 3 4WARD trial of mavorixafor in CN, we continue to expect full enrollment in the third or fourth quarter of this year and potential top-line data in late 2026,” Arbert-Engels said.1

References

1. X4 Pharmaceuticals, Inc. X4 Pharmaceuticals Granted Fast Track Designation for Mavorixafor for the Treatment of Chronic Neutropenia by U.S. FDA. June 10, 2025. Accessed June 10, 2025. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-granted-fast-track-designation-mavorixafor

2. Campbell, P. FDA Approves Mavorixafor (XOLREMDI) as First Drug Indicated for WHIM Syndrome. April 29, 2024. Accessed June 10, 2025. https://www.hcplive.com/view/fda-approves-mavorixafor-first-drug-indicated-for-whim-syndrome

3. X4 Pharmaceuticals, Inc. X4 Pharmaceuticals Announces Positive Results from Completed 6-Month Phase 2 Trial of Mavorixafor in Chronic Neutropenia (CN). November 13, 2024. Accessed June 10, 2025. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-positive-results-completed-six