Norgine gets first EU approval for WHIM syndrome therapy

Patients in the EU with the ultra-rare disease WHIM syndrome now have their first approved treatment, after Norgine's Xolremdi was cleared by the European Commission.

Oral CXCR4 antagonist Xolremdi (mavorixafor) – licensed from X4 Pharma of the US – can be used to treat patients aged 12 and over with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, a congenital, primary immunodeficiency characterised by low neutrophil counts.

It is caused by a mutation in the gene for CXCR4, a chemokine receptor involved in immune functioning and, as its name suggests, leads to warts, recurrent infections, and bone marrow problems, as well as some forms of cancer. The drug is thought to work by mobilising white cells from the bone marrow into the blood.

It is estimated that there are fewer than 500 people with WHIM in the EU, according to figures from the EMA. However, because WHIM is often undiagnosed or misdiagnosed, the actual number of people with the genetic mutation may be higher than those currently in patient registries.

Netherlands-headquartered Norgine's chief executive, Janneke van der Kamp, said the approval is a "meaningful milestone" for WHIM patients in the EU, adding that the company will now work with "health authorities, healthcare professionals and the rare disease community to help make mavorixafor available to eligible patients as quickly as possible."

In the phase 3 4WHIM study, which enrolled 31 adolescents and adults with the disease, a 200 mg once-daily dose of Xolremdi raised the time above the threshold for absolute neutrophil count (TAT-ANC) of 500 cells per mL – the trial's primary endpoint.

Norgine licensed rights to Xolremdi in Europe, Australia and New Zealand in early 2025 for €28.5 million ($33 million) upfront, a few months after X4 picked up its first approval for the drug in the US. Under the terms of the agreement, X4 could receive up to €226 million, contingent upon the achievement of regulatory and commercial milestones, plus double-digit royalties on sales in the licensed territories.

The drug made $6.5 million in US sales in 2025, its first full year on the market, with $2.3 million of that total coming in the fourth quarter.

Xolremdi is also being developed for chronic neutropenia in the phase 3 4WARD trial, which is expected to yield results in the latter half of this year, and Norgine will also have rights in its territories for that indication, if approved.

X4 has previously said that expanding Xolremdi's label to include chronic neutropenia could unlock a $1 to $2 billion global market in the US alone, where there are an estimated 15,000 patients, compared to fewer than 1,000 with WHIM.