New FDA Approval: XOLREMDI™
1 minute
The Food and Drug Administration (FDA) recently approved XOLREMDI™ – a CXC chemokine receptor 4 (CXCR4) antagonist 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.
Read the InpharmD clinical summary below:
| Drug Name |
XOLREMDI™ (mavorixafor) |
| Active Ingredient |
mavorixafor |
| Date of Approval |
April 26, 2024 |
| Manufacturer |
X4 Pharmaceuticals, Inc. |
| Approval Pathways and Indications |
Indication: XOLREMDI™ is a CXC chemokine receptor 4 (CXCR4) antagonist 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.
Approval Pathway: NDA |
| Therapeutic Class |
CXC Chemokine Receptor 4 (CXCR4) Antagonist |
| Formulation |
Capsules |
| MoA |
Mavorixafor is an orally bioavailable 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. |
| Dosing and Administration |
Capsules: 100 mg
Recommended dosage:
• Weight more than 50 kg: 400 mg orally once daily.
• Weight less than or equal to 50 kg: 300 mg orally once daily.
• Administer XOLREMDI™ on an empty stomach after an overnight fast, and at least 30 minutes before food. |
| Administered by self or by HCP |
Administered by self |
| Place in Therapy |
Prior to XOLREMDI™, 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. XOLREMDI™ is a targeted treatment that has demonstrated the ability to elevate absolute neutrophil and lymphocyte counts, increasing WHIM patients’ ability to fight infections. |
| Expected Market Launch Date |
Anticipated availability is currently unknown. |
| New Molecular Entity (NME) or Existing Formulation |
NME |
| Expected Cost |
Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
The efficacy of XOLREMDI™ in patients aged 12 years and older with WHIM syndrome was demonstrated in the 52-week, randomized, double-blind, placebo-controlled portion of Study 1 [NCT03995108]. Enrolled patients had a genotype-confirmed variant of CXCR4 consistent with WHIM syndrome, and a confirmed absolute neutrophil count (ANC) ≤400 cells/µL. Patients were permitted to continue (but not initiate) immunoglobulin therapy at the same dose. Use of other CXCR4 antagonists was not permitted.
Thirty-one patients were randomized 1:1 to receive either placebo (N=17) or XOLREMDI™ (N=14) once daily for 52 weeks. The efficacy of XOLREMDI in the treatment of patients with WHIM syndrome was based on improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections. For ANC, the mean time (hours) above ANC threshold (TAT-ANC) of 500 cells/μL over a 24-hour period was assessed 4 times throughout the study (every 3 months for 12 months). The results over the 52- week period showed that TAT-ANC was statistically significantly greater in patients treated with XOLREMDI™ (LS mean [SE] 15.0 [1.89] hours) compared with placebo (2.8 [1.52] hours) (p value <0.0001).
For ALC, the mean time (hours) above ALC threshold (TAT-ALC) of 1,000 cells/μL over a 24-hour period was assessed 4 times throughout the study (every 3 months for 12 months). The results over the 52-week period showed that TAT-ALC was statistically significantly greater in patients treated with XOLREMDI™ (LS mean [SE] 15.8 [1.39] hours) compared with placebo (4.6 [1.15] hours) (p value <0.0001). |
| Sources |
X4 Pharmaceuticals announces FDA approval of XOLREMDITM (mavorixafor) capsules, first drug indicated in patients with WHIM syndrome. X4 Pharmaceuticals, Inc. (2024, April 29). https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-fda-approval-xolremditm-mavorixafor |
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