With the approval of X4 Pharmaceuticals’ first product mavorixafor, there’s a new commercial rare disease player in town.
Following a 10-year development journey, the FDA on Monday approved mavorixafor in patients 12 and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis).
The oral drug will be sold under the brand name Xolremdi at a wholesale acquisition cost (WAC) of $496,400 per year for patients that weigh more than 50 kg and around $372,300 for patients less than or equal to 50 kg, according to a securities filing.
With the approval, Xolremdi has become the first drug specifically FDA-approved to treat WHIM, which is a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by an oversignaling of the CXCR4 pathway. The condition causes white blood cells to get stuck in a patient’s bone marrow, preventing them from circulating and protecting the body from infection.
The syndrome is named for its four classic manifestations: warts, hypogammaglobulinemia (low antibody levels), infections, and myelokathexis (low white blood cell count). Because WHIM patients characteristically have low blood levels of neutrophils and lymphocytes, they often struggle with serious and frequent infections. WHIM patients who suffer repeated infections may potentially develop loss of lung function and hearing loss.
In an interview with Fierce Pharma, X4 president and CEO Paula Ragan, Ph.D., likened living with the condition to the world’s initial experience with COVID-19, when infections could become “life-threatening at any moment.”
Up until now, treatment of WHIM has been targeting the symptoms, often involving antibiotics or immunoglobulins, Ragan explained.
Xolremdi, as a CXCR4 inhibitor, seeks to tackle the root cause of WHIM by dampening the oversignaling pathway and allowing white blood cells to move out of the bone marrow and into the bloodstream to circulate, survey for infection and hopefully nip it in the bud, Ragan said. X4 also figures Xolremdi could enhance patients’ long-term immune memory, potentially helping them both acutely and chronically, she added.
Results from the phase 3 4WHIM study showed that Xolremdi helped slash infection rates and raise patients’ levels of neutrophils and lymphocytes.
X4 currently estimates that there are around 1,000 WHIM patients in the U.S. However, given the ultra-rare nature of the disease and the fact that it is likely underdiagnosed, “we will ultimately know what the true prevalence is once the drug is approved over many years,” Ragan said, suggesting “if you build it, they will come.”
To prepare for Xolremdi’s approval, X4 has been working to improve education and awareness around the disease, including the website What if it’s WHIM, Ragan pointed out. X4 is also offering free genetic testing in a bid to identify more WHIM patients, she added.
As for the company’s launch plans, “we are ready day one,” Ragan said. X4 has been hiring and training its field force of about two dozen people to cover the entire U.S. in advance of the FDA decision, and it has been building products in channel to support the launch, Ragan said.
Xolremdi’s approval marks the culmination of a decade-long journey for X4, which broke cover back in 2015 after picking up mavorixafor—then known as X4P-001—from Sanofi.
Ragan now expects the drug’s approval to show that X4 is “not only capable of R&D but a sustainable R&D commercial business that can hopefully join the ranks of many of these great companies [that] brought truly impactful rare disease therapies to the business like Vertex and BioMarin and others.”
Aside from WHIM, X4 is also testing mavorixafor in chronic neutropenia, with plans to kick off a late-stage trial in the condition later this year, Ragan said. Additionally, the Xolremdi approval has furnished X4 with a priority review voucher, which the company could use to secure a speedy FDA review on another regulatory filing or potentially sell to another drugmaker.