FDA Approves Mavorixafor (XOLREMDI) as First Drug Indicated for WHIM Syndrome

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FDA approves mavorixafor (XOLREMDI) for WHIM syndrome, the first approved treatment for the rare disease.

US FDA logo in black over a white background. | Credit: US Food and Drug Administration

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved mavorixafor (XOLREMDI) capsules for the treatment of WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) in patients aged 12 years or older.

Announced by X4 Pharmaceuticals on April 29, 2024, the decision makes the CXC chemokine receptor 4 antagonist the first therapy specifically indicated in patients with WHIM syndrome and is based on data from the phase 3 4WHIM trial.1

“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,” said Teresa K. Tarrant, MD, associate professor of Medicine, Rheumatology, and Immunology at Duke University School of Medicine.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.”

Specifically indicated to increase the number of circulating mature neutrophils and lymphocytes in patients 12 years or older with WHIM syndrome, mavorixafor had been granted a Breakthrough Therapy Designation and its application for approval, which was submitted in September 2023, was evaluated under Priority Review. The approval was based on data from the phase 3, global, randomized, double-blind, placebo-controlled 4WHIM trial.1,2

Launched in 2019, the 4WHIM trial randomized 31 people aged 12 years and older diagnosed with WHIM syndrome in a 1:1 ratio to 400 mg mavorixafor (n=14) or placebo (n=17) orally once daily for 52 weeks. The trial’s primary outcome of interest was the effect of treatment on time above threshold (≥500 cells/microliter) for absolute neutrophil count (TATANC) relative to placebo therapy over 24-hour periods at 4 time points throughout the 52-week trial.1,3,4

Results of the trial suggested use of mavorixafor was associated with a clinically and statistically superior effect relative to placebo, with use associated with increased TATANC)(P <.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count (P <.0001). Additional analyses from the trial suggested used was associated with improved total infection score and total wart change score using a win-ratio method.1,3

According to the release from X4 Pharmaceuticals, mavorixafor is contraindicated with drugs highly dependent on CYP2D6 for clearance and the most common adverse reactions with use were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness. The company noted plans to make the agent commercially available in the US through their specialty pharmacy partner PANTHERx® Rare.1

“Effective and innovative treatments are critical for those diagnosed with a primary immunodeficiency. The approval of XOLREMDI marks an important advancement for people living with WHIM syndrome, who are susceptible to serious and frequent infections,” said Jorey Berry, president and chief executive officer of the Immune Deficiency Foundation.1 “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.”

References:

  1. X4 Pharmaceuticals, Inc. X4 Pharmaceuticals announces FDA approval of XOLREMDITM (mavorixafor) capsules, first drug indicated in patients with WHIM syndrome. X4 Pharmaceuticals, Inc. 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, Inc. X4 Pharmaceuticals announces submission of New Drug Application (NDA) to U.S. FDA for mavorixafor in whim syndrome. X4 Pharmaceuticals, Inc. September 5, 2023. Accessed April 29, 2024. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-submission-new-drug-application-nda.
  3. X4 Pharmaceuticals, Inc. X4 Pharmaceuticals announces positive phase 3 results showing mavorixafor reduced the rate, severity, and duration of infections vs. placebo in participants diagnosed with Whim Syndrome. X4 Pharmaceuticals, Inc. May 16, 2023. Accessed April 29, 2024. https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-positive-phase-3-results-showing.
  4. Efficacy and safety study of MAVORIXAFOR in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (whim) syndrome - full text view. ClinicalTrials.gov. Accessed April 29, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03995108.
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