X4 cues up FDA verdict in April for WHIM syndrome drug

The FDA has started a priority review of X4 Pharma’s mavorixafor, angling to become the first therapy for the rare disease WHIM syndrome, with a decision due by 30th April next year.

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare congenital immunodeficiency that affects fewer than 1,000 people in the US and is caused by a mutation in the gene for CXCR4, a chemokine receptor involved in immune functioning.

As its name suggests, patients with WHIM syndrome are prone to developing warts, recurrent infections and bone marrow problems, as well as some forms of cancer, and have persistently low counts of white blood cells called neutrophils (neutropenia).

Mavorixafor is an oral antagonist of CXCR4 and, if approved, could be the first drug that targets the underlying mechanism in the disease.

At the moment, WHIM patients are treated off-label with injectable G-CSF or GM-CSF drugs like filgrastim or sargramostim to combat neutropenia, or receive immunoglobulin replacement therapy delivered by injection or infusion, and tend to need regular antibiotics to reduce the frequency of chronic bacterial infections.

X4’s FDA filing draws on a phase 3 clinical trial – codenamed 4WHIM – that enrolled 31 adolescents and adults with the disease and compared a 200 mg dose of mavorixafor given once daily to a placebo for 52 weeks, followed by an open-label trial extension.

The study met its primary endpoint of time above threshold for absolute neutrophil count (TAT-ANC) of 500 cells per ml compared to placebo, as well as a secondary endpoint looking at counts above 1,000 cells per ml. It was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events.

More than 90% of the eligible participants opted to receive treatment with mavorixafor in the open-label extension phase.

X4’s chief executive Paula Ragan said the company will work closely with the FDA during the review “with the goal of bringing mavorixafor to people with WHIM syndrome as quickly as possible.”

If approved, the programme could provide X4 with a coveted FDA priority review voucher (PRV) that can be used to reduce the standard review time to six months and can be worth over $100 million if sold to another drug developer.

WHIM syndrome is hard to diagnose, particularly as patients may not exhibit all the characteristic symptoms, so X4 may have its work cut out identifying patients eligible for treatment with the drug.

The company is planning to extend its uses into other disorders and has a phase 3 programme on the go in patients with idiopathic, cyclic and congenital neutropenia. GlobalData has predicted sales could reach around $70 million in 2033.