FDA approves first drug for WHIM syndrome, a rare disorder that can lead to recurrent, life-threatening infections

Action

The U.S. Food and Drug Administration has approved Xolremdi (mavorixafor) capsules in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.

Disease or Condition

WHIM syndrome is a rare genetic disease that causes the body’s immune system to not function properly. WHIM syndrome reduces the number of mature neutrophils and lymphocytes (types of white blood cells important in fighting infection) circulating within the body. It is estimated to occur in about 1 in 5 million live births. Approximately 60 cases have been reported in the medical literature.

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.

Effectiveness

The effectiveness of Xolremdi was evaluated in a 52-week, randomized, double-blind, placebo-controlled trial that enrolled 31 adolescents and adults with WHIM syndrome (NCT03995108). Xolremdi improved absolute neutrophil counts and absolute lymphocyte counts, assessed over a 24-hour period four times throughout the study. Absolute neutrophil counts below 500 cells/µL and absolute lymphocyte counts below 1000 cells/µL are associated with an increased risk of infections. The average length of time over 24 hours that counts were above these levels was significantly longer with Xolremdi compared to the placebo group (15.0 hours compared to 2.8 hours for absolute neutrophil counts; 15.8 hours compared to 4.6 hours for absolute lymphocyte counts).

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.

Safety Information

The most frequently reported adverse reactions were thrombocytopenia (low platelet counts), rash, rhinitis (stuffy nose), epistaxis (nosebleed), vomiting, and dizziness. Xolremdi can cause fetal harm, so women of childbearing potential should be advised to use effective contraception. Xolremdi can also interact with some medicines, supplements, and grapefruit. Consult the prescribing information for more details about Xolremdi’s risks.

Designation

This application received priority review, Fast Track, Rare Pediatric Disease, and orphan drug designations.