• 27 Jan 2025
• Admin
• News Article

EMA Validates X4 Pharma’s Marketing Authorization Application

X4 Pharmaceuticals, a company driven to improve the lives of people with rare diseases of the immune system, announced that its Marketing Authorization Application (MAA) for mavorixafor for the treatment of WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis), a rare primary immunodeficiency, has been validated for review and is now under evaluation with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The EMA previously granted orphan designation to mavorixafor in WHIM syndrome. In April 2024, mavorixafor received US Food and Drug Administration approval as Xolremdi, an oral, once-daily treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes.

“Making mavorixafor available to those in the European Union living with WHIM syndrome is a top priority for X4 and this submission demonstrates our continued ability to deliver on our key milestones and generate growth,” said Paula Ragan, Ph.D., president and chief executive officer of X4 Pharmaceuticals. “With our MAA now validated for review by the EMA, we expect to enable our recently announced European partner, Norgine, to provide this much-needed treatment to patients as rapidly as possible should it be approved. We look forward to working alongside the EMA as they assess our application.”

Mavorixafor is a small-molecule antagonist of the CXCR4 receptor being developed as a once-daily oral therapy for people with rare primary immunodeficiencies, including WHIM syndrome. The global, pivotal, 4WHIM phase 3 trial that X4 conducted met its primary endpoint, a key secondary endpoint, and was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events. Additionally, in the 4WHIM trial, once-daily oral mavorixafor resulted in reductions in the rate, severity, and duration of infections in participants with WHIM syndrome.

If approved by the EMA, mavorixafor would be the first drug indicated for patients with WHIM syndrome in Europe, a population estimated to be approximately 1,000 people. Earlier this month X4 announced an exclusive licensing and supply agreement with Norgine to commercialize mavorixafor in Europe, Australia, and New Zealand.

WHIM syndrome is a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 receptor dysfunction that results in impaired mobilization of white blood cells from the bone marrow into peripheral circulation. WHIM syndrome is named for its four classic manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, although only a minority of patients experience all four manifestations in the acronym. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience serious and/or frequent infections. It is estimated that at least 1,000 people are currently diagnosed with WHIM syndrome in the US, with another 1,000 estimated in Europe.

Xolremdi (mavorixafor) is a selective CXCR4 receptor antagonist approved in the US as an oral, once-daily treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. CXCR4 receptor stimulation by its ligand, CXCL12, has been shown to play a key role in the movement of white blood cells (leukocytes) to and from the bone marrow compartment. Treatment with Xolremdi results in increased mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation.

X4 Pharmaceuticals is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs.