HQ Team
April 30, 2024: The Food and Drug Administration has cleared X4 Pharmaceutical’s drug to treat a rare genetic disease that occurs in one in five million births.
The WHIM syndrome — warts, infections, hypogammaglobulinemia and myelokathexis — causes the body’s immune system not to function properly, according to an FDA statement.
The US health regulator approved the drug branded as Xolremdi, chemically known as mavorixafor, for patients above 12 years of age.
The effectiveness of Xolremdi was evaluated in a 52-week trial that enrolled 31 adolescents and adults with WHIM syndrome.
Blood cell count
Xolremdi improved absolute neutrophil counts and absolute lymphocyte counts, assessed over 24 hours four times throughout the study, the FDA stated.
Infection scores were calculated for each patient based on their infection rate and infection severity.
Xolremdi decreased the infection score by 40% over the 52-week treatment period compared to placebo. Xolremdi did not improve warts, according to the FDA statement.
The drug increases the number of circulating mature neutrophils and lymphocytes in the body. The disease reduces both the types of white blood cells that fight infections.
While symptoms vary, patients with WHIM syndrome can have recurrent infections, including pneumonia, sinusitis, and skin infections and are at risk for life-threatening bacterial and viral infections.
Breakthrough Therapy Designation
The FDA had granted Breakthrough Therapy Designation to mavorixafor in WHIM syndrome.
It evaluated the New Drug Application under Priority Review, a designation for therapies that have the potential to provide significant improvement in the treatment, diagnosis, or prevention of serious conditions.
According to the National Organisation for Rare Disorders patients with WHIM syndrome are more susceptible to potentially life-threatening bacterial infections.
To a lesser extent, they are also predisposed to viral infections. Affected individuals are particularly susceptible to human papillomavirus, which can cause skin and genital warts and potentially lead to cancer.
Affected individuals have extremely low levels of certain white blood cells (neutrophils) leading to a condition called neutropenia. In most patients, WHIM syndrome is caused by changes (mutations) in the CXCR4 gene.
$496,400 a year
In the US the the drug is set to cost $496,400 on an annual basis for patients greater than 50 kilograms, reflecting a 400 milligram daily dose.
It will cost $372,300 for patients less than or equal to 50 kilograms, reflecting a 300-milligram daily dose, according to Securities and Exchange Commission filing.
Teresa K. Tarrant, MD, Associate Professor of Medicine, Rheumatology, and Immunology at Duke University School of Medicine and a principal investigator in the 4WHIM trial said the main outcome was that the patients would now be able to fight infections.
“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.
“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 said.
