FDA Approves Mavorixafor for Treatment of WHIM Syndrome


WHIM syndrome is characterized by low levels of neutrophils and lymphocytes in the blood due to dysfunction in the CXCR4 receptor, which results in serious and frequent infections.

The FDA approved mavorixafor (Xolremdi) to treat warts, hypogammaglobulinemia, infections and myelokathexi (WHIM) syndrome in patients 12 years of age or older, X4 Pharmaceuticals announced in a release.1 Mavorixafor is the first approved therapy that’s specifically indicated for patients with the rare inherited immunodeficiency disease.

FDA Approves Mavorixafor for Treatment of WHIM Syndrome / everythingpossible - stock.adobe.com

FDA Approves Mavorixafor for Treatment of WHIM Syndrome / everythingpossible - stock.adobe.com

WHIM syndrome is characterized by low levels of neutrophils and lymphocytes in the blood due to dysfunction in the CXCR4 receptor, which results in serious and frequent infections. There are currently around 1000 patients in the United States diagnosed with the disease. Mavorixafor is a small-molecule selective CXCR4 receptor antagonist that helps to increase the mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation.

About 4WHIM

Trial Name: Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome

Clinicaltrials.gov Identifier: NCT03995108

Sponsor: X4 Pharmaceuticals

Summary: This study has a double-blind, Randomized Placebo-Controlled Period and an Open-Label Period. The primary objective of the Randomized Placebo-Controlled Period is to demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by increasing levels of circulating neutrophils compared with placebo, and relative to a clinically meaningful threshold. The primary objective of the Open-Label Period is to evaluate the safety and tolerability of mavorixafor in participants with WHIM syndrome. Participants are allowed to continue treatment in the Open-Label Period, if regionally applicable, until mavorixafor becomes commercially available, or until the study is terminated by the Sponsor.

“Until now, supportive care for people with WHIM syndrome has focused on symptom management and not the underlying cause of disease—the dysfunction of the CXCR4 pathway,” Teresa K. Tarrant, MD, a principal investigator in the 4WHIM trial, said in a release.1 “I am thrilled that with the approval of Xolremdi, a therapy designed to address dysregulated CXCR4 pathway signaling, we now have a targeted treatment that has demonstrated the ability to elevate absolute neutrophil and lymphocyte counts, increasing WHIM patients’ ability to fight infections.”

The approval of mavorixafor was based on data from the 4WHIM trial (NCT03995108), in which the therapy met its primary endpoint of time above threshold for absolute neutrophil count versus placebo. Mavorixafor treatment also resulted in reductions in the rate, severity, and duration of infections, and was generally well-tolerated with no treatment-related serious adverse events.2

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The 4WHIM trial was a phase 3, randomized, double-blind, multicenter, placebo-controlled study that evaluated the efficacy and safety of mavorixafor in patients aged 12 years and older diagnosed with WHIM. The study cohort included 31 patients with confirmed CXCR4 variant and absolute neutrophil count or total white blood cell count of ≤400 cells/µL. Patients randomly received mavorixafor 400 mg once daily or placebo for 52 weeks.

The study found that, of 14 patients who received treatment, mean absolute white blood cell counts, absolute neutrophil counts, and absolute lymphocyte counts increased from baseline into normal range and were sustained at each assessed time point over the study period. Compared to placebo, those treated with mavorixafor had a 60% lower annualized infection rate and a 40% lower total infection score, which was defined as a combination of infection number and severity.3

The most common adverse reactions reported by patients treated with mavorixafor included thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.

“Effective and innovative treatments are critical for those diagnosed with a primary immunodeficiency,” Jorey Berry, president and CEO of the Immune Deficiency Foundation, said in a release.1 “The approval of Xolremdi marks an important advancement for people living with WHIM syndrome, who are susceptible to serious and frequent infections. We are very pleased to have been a partner to X4 in their journey to bring this much-needed treatment to this underserved rare disease community.”

READ MORE: FDA Updates Resource Center

1. X4 Pharmaceuticals Announces FDA Approval of XOLREMDI™ (mavorixafor) Capsules, First Drug Indicated in Patients with WHIM Syndrome. News Release. X4 Pharmaceuticals. April 29, 2024. Accessed April 29, 2024. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-fda-approval-xolremditm-mavorixafor
2. X4 Pharmaceuticals Announces FDA Acceptance with Priority Review of U.S. NDA for Mavorixafor in WHIM Syndrome. News Release. X4 Pharmaceuticals. October 31, 2023. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-fda-acceptance-priority-review-us
3. Badolato R, Donadieu J. S180: RESULTS OF A PHASE 3 TRIAL OF AN ORAL CXCR4 ANTAGONIST, MAVORIXAFOR, FOR TREATMENT OF PATIENTS WITH WHIM SYNDROME. Hemasphere. 2023;7(Suppl ):e684700a. Published 2023 Aug 8. doi:10.1097/01.HS9.0000967632.68470.0a
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