The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for mavorixafor (X4P-001) to treat adults with WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome.
A Breakthrough Therapy Designation is awarded to treatments in which preliminary clinical evidence demonstrates that it may provide substantial improvements over any available therapy on at least one clinically significant endpoint. With this designation, the FDA will expedite the review process from the standard 10 months to 6 months. That review process has not started yet since the drug is being investigated in a Phase III clinical trial. However, data from the Phase II study presented at the 23rd Congress of the European Hematology Association (EHA) in June 2018 showed the drug to be safe and effective.
WHIM syndrome is a primary immunodeficiency disease due to mutations in the CXCR4 receptor gene. The syndrome is named for the characteristic symptoms often present – Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Due to the nature of the symptoms, it can be years before these patients are properly diagnosed.
In an exclusive interview with CheckRare, Lynne Kelley, MD, FACS, Chief Medical Officer of X4 Pharmaceuticals said, “There are probably a number of patients that are seen by pediatricians, internal medicine, or primary care doctors – they don’t know that the patient has a potentially treatable issue because they’re seeing them for independent infections.”
Dr. Kelley noted that children with undiagnosed WHIM syndrome may be a child with two or three infections over the course of the year or a series of multiple ear infections, or have warts that do not respond to standard therapy. In that regard, Dr. Kelley and her team are raising awareness about the condition to the medical community to let them know that a treatment option is in development for this rare condition. “To get the diagnosis, you have to have the genetic test and you also have to have the doctor be aware that there’s a genetic test available and that requires putting all the pieces together.”
Mavorixafor is a CXCR4 antagonist that specifically targets the pathophysiology of WHIM syndrome.
Dr Kelley said, “The CXCR4 receptor is a critical component of immune cell trafficking,” said Dr. Kelley, adding that in WHIM syndrome, there is gain of function mutation in the receptor so that the receptor is always on and mavorixafor is an allosteric inhibitor than can turn the receptor off allowing WHIM syndrome patients to transition towards more normal immune cell movement.
If left untreated, symptoms will only worsen, and many will be at greater risk of developing HPV-related cervical cancer and lymphomas. The constant ear infections can also lead to permanent deafness. There is currently no approved therapy for WHIM syndrome, and current standards of care are limited to treatment of acute infections with antibiotics or prevention of infections mainly through immunoglobulin substitution or G-CSF.
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