Clinical-stage biopharma company X4 Pharmaceuticals announced the initiation of a Phase 1b clinical trial of mavorixafor (X4P-001) for the treatment of Severe Congenital Neutropenia (SCN), a group of rare blood disorders characterized by abnormally low levels of neutrophils.
The Phase 1b trial is a 14-day, proof-of-concept trial designed to assess the safety and tolerability of daily, oral mavorixafor in participants with SCN and other selected congenital neutropenia disorders. In addition, the trial will evaluate the neutrophil response in this patient population as an independent agent or in combination with granulocyte-colony stimulating factor (G-CSF). The trial will enroll up to 45 patients in total. mavorixafor (X4P-001), is a potential first-in-class, once-daily, oral inhibitor of CXCR4, currently in a Phase 3 clinical trial for the treatment of WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene.
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40% of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.
According to the NIH, approximately 20% of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence. Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.
In a press release, Lynne Kelley, MD, FACS, Chief Medical Officer of X4 Pharmaceuticals said, “SCN often presents as a diagnostic challenge for physicians, and there is an unmet clinical need for targeted treatment options that may be better tolerated than existing therapies. Current treatments are limited to non-specific stimulation of the bone marrow with daily injections of G-CSF and antibiotics for infections, although G-CSF can cause bone pain as well as injection site reactions. Additionally, in rare instances, high chronic doses of G-CSF have been associated with myelodysplasia and acute myeloid leukemia in this patient population. We are interested in exploring whether mavorixafor may provide a safe and well-tolerated treatment alternative for these patients.”
About Severe Congenital Neutropenia
Severe Congenital Neutropenia (SCN) comprises a group of rare hematological diseases that may result from mutations in many different genes. These genes play a role in the maturation and function of neutrophils. In these patients, neutropenia may result from impaired maturation of neutrophils, increased cell death, or impaired function. Affecting an estimated 2,000 to 3,000 people in the US and Europe, patients with SCN are prone to recurrent, often life-threatening infections beginning in their first months of life. Patients with SCN may be treated with daily sub-cutaneous injections of G-CSF, which causes bone pain in a subset of patients and may increase the risk of myelodysplasia and acute myeloid leukemia.
