NewsFlash – Xolremdi Approved to Treat WHIM Syndrome

The U.S. Food and Drug Administration (FDA) approved X4 Pharmaceuticals’ Xolremdi^™ (mavorixafor) capsules on April 26, 2024. A selective CXC chemokine receptor 4 (CXCR4) antagonist, it treats the extremely rare condition known as warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome. Indicated for patients as young as 12 years old, the recommended dose of Xolremdi is 300mg (three capsules) for those who weigh 50kg (110 pounds) or less; and 400mg (four capsules) for patients weighing more than 50kg. All capsules should be taken in the morning after no food during the night and one-half hour or more before breakfast. An exact launch date has not been announced, but the manufacturer actively is contacting specialists to inform them about WHIM syndrome and Xolremdi. Its wholesale acquisition cost (WAC) is $340 per capsule. Complete prescribing information for Xolremdi is here.

At a Glance

• Brand (Generic) Name: Xolremdi (mavorixafor)
• Manufacturer: X4 Pharmaceuticals
• Date Approved: April 26, 2024
• Indication: to increase the number of circulating mature neutrophils and lymphocytes for patients at least 12 years old who have WHIM syndrome
• Dosage Forms Available: 100mg oral capsules
• Launch Date: not yet available
• Estimated Annual Cost: $372,300 for the 300mg/day dose; $496,400 for 400mg/day
• WHIM syndrome is an inherited autoimmune disease caused by mutations in the CXCR4 gene. Overactivity of CXCR4 traps mature neutrophils and leucocytes in the bone marrow, so fewer reach general circulation.
• Characterized by low blood levels of neutrophils and leucocytes, WHIM syndrome predisposes patients to recurring, often serious, bacterial infections, as well as to human papillomavirus (HPV) infections.
• Although symptoms typically appear in young children, diagnosis often is delayed because symptoms are vague, general, and inconsistent.
• X4 Pharmaceuticals estimates that WHIM syndrome is currently diagnosed in approximately 1,000 Americans.
• Xolremdi blocks CXCR4 to help release active neutrophils and leucocytes into the bloodstream from bone marrow.
• Among the 31 patients in the phase III 4WHIM clinical study, more of those taking Xolremdi achieved and maintained target levels of neutrophils and lymphocytes than participants who were taking placebo capsules. Additionally, patients taking the active drug averaged a 60% drop in their annualized infection rates over one year.
• The most frequent side effects for participants in clinical trials were dizziness, low platelets, nose bleeds, rashes, rhinitis, and vomiting.
• No other drugs are approved to treat the cause of WHIM syndrome.
• Plerixafor injection, a CXCR4 inhibitor indicated to move stem cells into peripheral circulation before a stem cell transplant, is used off-label for some patients who have WHIM.
• Other current therapy includes immunoglobulin replacement to help prevent infections, a granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), to increase neutrophil counts and standard treatments for infections and other symptoms of WHIM syndrome.
• Patients also should be vaccinated against bacterial infections and HPV.
• With a Breakthrough Therapy designation, Xolremdi was approved under the FDA’s Priority Review process. It also was granted a Rare Pediatric Disease Priority Review Voucher that X4 Pharmaceuticals can use to expedite a future new drug application or sell to another company.