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The FDA approved mavorixafor (Xolremdi) capsules as the first therapy specifically for WHIM syndrome, a rare primary immunodeficiency and chronic neutropenic disorder, on Monday.

Caused by CXC chemokine receptor 4 (CXCR4) pathway dysfunction, WHIM syndrome manifests as warts, hypogammaglobulinemia, infections, and myelokathexis. The syndrome is characterized by neutropenia and lymphopenia that makes patients susceptible to life-threatening bacterial infections and human papillomavirus (HPV).

Mavorixafor, a selective CXCR4 antagonist, is designed to increase circulating mature neutrophils and lymphocytes and thereby reduce the risk of infection in patients 12 years and up.

The supported the approval. The multinational phase III study randomized 31 patients at least 12 years of age to mavorixafor or placebo, with the CXCR4 antagonist demonstrating significant improvements in neutrophil and lymphocyte counts.

Over 52 weeks, patients assigned to mavorixafor experienced increased time above threshold for absolute neutrophil counts (≥500 cells/μl) and absolute lymphocyte counts (≥1,000 cells/μl; P<0.0001 for both):

• Neutrophils: least squares (LS) mean 15 vs 2.8 hours
• Lymphocytes: LS mean 15.8 vs 4.6 hours

Furthermore, annualized infection rates were 60% lower with mavorixafor (LS mean 1.7 vs 4.2 with placebo) and total infection scores were 40% lower. No difference in total wart change score was demonstrated.

"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 investigator Teresa Tarrant, MD, of Duke University School of Medicine in Durham, North Carolina, in a statement from the drugmaker.

"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," she added.

Adverse events occurring in 10% or more of patients on mavorixafor, and more frequently than with placebo, included thrombocytopenia (21% vs none with placebo), pityriasis (14% vs none), rash (14% vs none), rhinitis (14% vs none), epistaxis (14% vs 6%), vomiting (14% vs 6%), and dizziness (14% vs 6%).

Mavorixafor comes in 100-mg capsules and should be taken on an empty stomach after fasting overnight and at least a half-hour prior to eating. According to the , the recommended dosage is 400 mg once-daily for individuals weighing more than 50 kg and 300 mg once-daily for those weighing 50 kg or less.

The selective CXCR4 antagonist is contraindicated with drugs highly dependent on CYP2D6 for clearance. Mavorixafor is expected to cause fetal harm and patients should be monitored for QTc interval prolongation. The drug is not recommended for those with severe renal or hepatic impairment.

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