X4 Pharmaceuticals, a partner of Abbisko Therapeutics, recently presented positive biomarker, efficacy and safety data from the ongoing Phase 2 trial of Mavorixafor in patients with WHIM syndrome at the 25th European Hematology Association (EHA) Annual Congress.

WHIM syndrome is a rare innate immune-deficient disease which usually cause the development of Warts, Hypogammaglobulinemia, Infections, and Myelokathexis in patients. C-X-C chemokine receptor 4 (CXCR4) mutations, which lead to aberrant activation CXCL12-CXCR4 signaling and subsequent inhibition of neutrophil release from bone marrow, are the major pathogenic factor for WHIM syndrome. By far, there are no approved targeted therapies on the market for this disease. 

Mavorixafor is a first-in-class, orally-available, small molecule antagonist of of CXCR4 . Inhibition of the CXCR4 receptor creates the potential for Mavorixafor to provide therapeutic benefit across a wide variety of diseases, including primary immunodeficiencies and certain types of cancer. Mavorixafor has demonstrated good safety and tolerability in nearly 200 patients in various clinical trials. Promising efficacy data from WHIM trials has been recognized by the U.S. FDA and led to a Breakthrough Therapy Designation. It also received an Orphan Drug Designation in the USA and the EU. The efficacy and safety of Mavorixafor are currently being evaluated in a global Phase 3 clinical trial in patients with WHIM syndrome, and in two Phase 1b clinical trials – in combination with ibrutinib in patients with Waldenström’s macroglobulinemia, and as monotherapy in patients with severe congenital neutropenia (SCN).

Clinical data highlight presented at EHA:

- Sustained, dose-dependent increases in WBC (white blood cells), ANC (absolute neutrophil count), and ALC (absolute lymphocyte count) were achieved;

- higher doses of Mavorixafor were shown to shorten the time to achieve number threshold of absolute ANC;

- A decreased yearly infection rate from 4.63 [95%CI 3.3,6.3] events in the 12 months prior to the trial, to 2.27 [95%CI 1.4, 3.5] events when treated with Mavorixafor at higher doses once daily;

- The patients with cutaneous warts on hands and/or feet at baseline achieved an average 75% reduction in the number of warts;

- Mavorixafor was well-tolerated for the extended duration of up to more than two years without any attributable serious adverse effects;