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General Information
Xolremdi (mavorixafor) is a CXC chemokine receptor 4 antagonist.
Xolremdi is specifically indicated in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.
Dosing/Administration
Xolremdi is supplied as capsules for oral administration. The recommended dosage of Xolremdi is:
- Weight more than 50 kg: 400 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food;
- Weight less than or equal to 50 kg: 300 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
Swallow the capsules whole. Do not open, break, or chew capsules.
If a dose of Xolremdi is missed, the next dose should be taken as scheduled. Do not take more than one Xolremdi dose each day.
Mechanism of Action
Xolremdi (mavorixafor) is an orally bioavailable CXC Chemokine Receptor 4 (CXCR4) antagonist that blocks the binding of the CXCR4 ligand, stromal-derived factor-1α (SDF-1α)/CXC Chemokine Ligand 12 (CXCL12). SDF-1/CXCR4 plays a role in trafficking and homing of leukocytes to and from the bone marrow compartment. Gain of function mutations in the CXCR4 receptor gene that occur in patients with WHIM syndrome lead to increased responsiveness to CXCL12 and retention of leukocytes in the bone marrow. Mavorixafor inhibits the response to CXCL12 in both wild‑type and mutated CXCR4 variants associated with WHIM syndrome. Treatment with mavorixafor results in increased mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation.
Side Effects
Adverse effects associated with the use of Xolremdi may include, but are not limited to, the following:
- thrombocytopenia
- pityriasis
- rash
- rhinitis
- epistaxis
- vomiting
- dizziness
Clinical Trial Results
The FDA approval of Xolremdi was based on results of the pivotal, 4WHIM Phase 3 clinical trial, a global, randomized, double-blind, placebo-controlled, 52-week multicenter study that evaluated the efficacy and safety of Xolremdi in 31 people aged 12 years and older diagnosed with WHIM syndrome. The efficacy of Xolremdi was determined by improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections. In the 4WHIM trial, Xolremdi treatment demonstrated increased time above threshold (≥500 cells/microliter) for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count (TAT-ALC) v. placebo (p<0.0001). The efficacy of Xolremdi was further assessed in a composite endpoint consisting of total infection score and total wart change score using a Win-Ratio method. Analyses of the individual components of this composite endpoint showed an approximate 40% reduction in total infection score, weighted by infection severity, in Xolremdi-treated patients compared with placebo-treated patients. There was no difference in total wart change scores between the Xolremdi and placebo treatment arms over the 52-week period. Treatment with Xolremdi also resulted in a 60% reduction in the annualized infection rate compared with placebo-treated patients.
Approval Date: 2024-04-01
Company Name: X4 Pharmaceuticals