Mavorixafor in WHIM Syndrome
X4 is developing mavorixafor as an oral, once-daily treatment for patients with WHIM syndrome. WHIM syndrome is a rare genetic primary immunodeficiency that results from “gain-of-function” mutations in the single gene that encodes for the CXCR4 receptor. These genetic mutations cause premature truncations in the CXCR4 protein, causing the receptor to remain in an “on” state longer than normal, resulting in compromised immune cell maturation and mobilization.
We have achieved clinical proof of concept for mavorixafor in a Phase 2 trial of WHIM syndrome where we observed reduction in severe neutropenia and significant lymphopenia; overall, mavorixafor was well tolerated. Additionally, patients experienced reduced infection rates, as reported by patients and the trial investigators. Substantial and visible reductions in wart lesions were also reported in a patient with a history of untreatable severe wart lesions. Based on the positive Phase 2 results, we initiated a global Phase 3 pivotal trial of mavorixafor in adults and pediatric patients with WHIM syndrome (4WHIM) and have now completed enrollment in the trial.
Currently, there are no approved therapies for the treatment of WHIM syndrome. Care is limited to the treatment of the different symptoms of WHIM and is mainly focused on the prevention and management of infections. None of these treatments, however, has been clinically proven to be effective for treating WHIM nor do they address the underlying cause of this multi-faceted disease, the genetic defect of the CXCR4 receptor. Mavorixafor has the potential to become the first disease-modifying therapy for the WHIM syndrome community.