Norgine announced that the European Commission has granted marketing authorization for Xolremdi (mavorixafor) for WHIM syndrome, making it the first therapy authorized for this condition in the European Union. The authorization, which follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use, was granted under exceptional circumstances given the ultra-rare nature of the disease. Norgine will lead commercialization across Europe under a licensing agreement with X4 Pharmaceuticals, the US-based company that originated and holds intellectual property rights to the molecule.
Xolremdi is indicated in patients aged 12 years and older for the treatment of WHIM syndrome — an acronym for warts, hypogammaglobulinemia, infections, and myelokathexis — to increase the number of circulating mature neutrophils and lymphocytes. The condition is caused by gain-of-function mutations in the CXCR4 receptor, which impairs the release of white blood cells from bone marrow into peripheral circulation, leaving affected individuals vulnerable to recurrent and severe infections. The EC authorization was granted under exceptional circumstances, a regulatory pathway applied when applicants cannot provide comprehensive efficacy and safety data due to the rarity of a condition; additional post-authorization data will be required.
The authorization is supported by results from NCT03995108, a Phase III randomized, double-blind, placebo-controlled, 52-week multicenter study that enrolled 31 patients aged 12 years and older with confirmed WHIM syndrome. The trial evaluated the efficacy and safety of mavorixafor against placebo, with results published in Blood in 2024 by Badolato and colleagues. The study met its primary endpoint, demonstrating that mavorixafor increased the duration of time that absolute neutrophil and lymphocyte counts remained above defined thresholds compared with placebo.
WHIM syndrome has until now been managed primarily through off-label use of filgrastim, a recombinant granulocyte colony-stimulating factor originally developed by Amgen that raises neutrophil counts but has no effect on lymphocytes, monocytes, or the wart burden associated with the condition. Plerixafor, a subcutaneously administered CXCR4 antagonist approved for stem cell mobilization, was evaluated in a Phase III crossover trial against G-CSF in WHIM syndrome but was not advanced to regulatory submission for this indication. Mavorixafor, as an oral once-daily CXCR4 antagonist that mobilizes both neutrophils and lymphocytes, occupies a distinct position as the only therapy carrying an approved label specifically for WHIM syndrome in either the US or the EU. X4 Pharmaceuticals received US FDA approval for Xolremdi in 2024. Beyond WHIM syndrome, mavorixafor is under active Phase III investigation in congenital and acquired chronic neutropenic disorders, with trial NCT06056297 currently recruiting.
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