Xolremdi (Mavorixafor) Is a New Treatment for the Rare Disorder WHIM Syndrome

Xolremdi (Mavorixafor) Is a New Treatment for the Rare Disorder WHIM Syndrome

X4 Pharma’s Xolremdi (mavorixafor) has received FDA approval, becoming the first drug specifically indicated for WHIM syndrome. This breakthrough treatment is set to improve the lives of patients with WHIM syndrome by increasing neutrophil and lymphocyte counts.

X4 Pharmaceuticals, based in Boston, is a clinical-stage biopharma company dedicated to developing and advancing innovative treatments for rare diseases. Recently, X4 announced that the US Food and Drug Administration (FDA) granted approval for its Xolremdi (mavorixafor) capsules.

This medication is designed for patients with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes. This approval marks a significant milestone as Xolremdi becomes the first drug specifically indicated for patients with WHIM syndrome.

“The approval of Xolremdi is a transformational milestone both for X4 and, more importantly, for the WHIM syndrome community,” said Paula Ragan, president and CEO of X4 Pharmaceuticals, in the company’s news release.

What Is WHIM Syndrome?

WHIM syndrome is a rare condition that involves primary immunodeficiency and chronic neutropenia. It is caused by dysfunction in the CXCR4 receptor, which hinders the effective release of white blood cells from the bone marrow into the peripheral circulation.

Individuals with WHIM syndrome typically exhibit low levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), leading to increased susceptibility to recurrent and severe infections. It is currently estimated that at least 1,000 individuals in the US are diagnosed with WHIM syndrome.

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How Does Xolremdi Work?

Xolremdi is designed to help patients with WHIM syndrome by increasing the number of mature neutrophils and lymphocytes in their bloodstream. It works by blocking a specific receptor called CXCR4, which normally binds to a substance called stromal-derived factor-1α (SDF-1α) or CXC chemokine ligand 12 (CXCL12). By blocking this receptor, Xolremdi prevents the usual response to CXCL12 that occurs in WHIM syndrome. This helps more neutrophils and lymphocytes move from the bone marrow into the bloodstream, where they can help fight infections.

Efficacy and Safety of Xolremdi

The FDA approved Xolremdi based on promising results from the 4WHIM Phase III clinical trial. Compared to the placebo, Xolremdi significantly increased the time above the threshold (≥500 cells/microliter) for absolute neutrophil count and the time above the threshold (≥1000 cells/microliter) for absolute lymphocyte count.

The trial also showed an approximate 40 percent reduction in the total infection score, weighted by severity, in patients treated with Xolremdi compared to those given the placebo. Additionally, Xolremdi treatment resulted in a 60 percent decrease in the annualized infection rate compared to placebo-treated patients.

Common adverse reactions among Xolremdi recipients included thrombocytopenia (low platelet counts), pityriasis (skin rash), rash, rhinitis (stuffy nose), epistaxis (nosebleed), vomiting and dizziness.

“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 CEO of the Immune Deficiency Foundation (IDF), in X4’s news release.

What Is the Price of Xolremdi?

X4 has set the annual wholesale acquisition cost (WAC) for Xolremdi at $496,400 for patients weighing more than 50 kilograms and $372,300 for patients weighing 50 kilograms or less.

Mavorixafor is also being tested for other conditions, including certain chronic disorders characterized by low levels of neutrophils.

According to Brookline Capital Markets analyst Leah Cann, approval to treat WHIM syndrome could result in sales of mavorixafor $54.6 million in 2024. With an additional approval for a second indication in 2025, sales could potentially grow to $450.9 million by 2027.

Current Treatment Options for WHIM Syndrome

Treating WHIM syndrome often involves immunoglobulin replacement therapy and drugs like granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF). These treatments help increase the production and maturation of neutrophils, reducing the risk of infections.

Mozobil (plerixafor), developed by Sanofi, works as a CXCR4 antagonist and is used with G-CSF to move hematopoietic stem cells into the bloodstream. A Phase III clinical trial showed that Mozobil might increase the absolute lymphocyte count (ALC) in WHIM patients more effectively than G-CSF. However, it did not perform better than G-CSF in reducing the total infection severity score (TISS) in WHIM patients.

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