European Regulators Recommend Approval of First WHIM Syndrome Treatment
Key Insights
The European Medicines Agency (search)'s CHMP issued a positive opinion recommending approval of mavorixafor (XOLREMDI (search)®) for WHIM syndrome (search) treatment in patients aged 12 years and older.
The recommendation is based on results from the pivotal Phase 3 4WHIM trial, which demonstrated significant improvements in neutrophil and lymphocyte counts and a 40% reduction in infection scores.
Final approval decision from the European Commission is expected in Q2 2026, potentially making this the first authorized treatment for WHIM syndrome (search) in Europe.
The European Medicines Agency (search)'s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of mavorixafor for treating WHIM syndrome (search) in patients aged 12 years and older, marking a significant milestone toward the first authorized treatment for this ultra-rare immune disorder in Europe.
The CHMP recommendation supports granting marketing authorization under exceptional circumstances for XOLREMDI (search)® (mavorixafor) to increase the number of circulating mature neutrophils and lymphocytes in WHIM syndrome (search) patients. The European Commission will now review the recommendation, with a final decision expected in the second quarter of 2026.
Addressing Critical Unmet Medical Need
WHIM syndrome (search) is an ultra-rare, inherited primary immunodeficiency (search) and chronic neutropenic disorder caused by CXCR4 (search) receptor dysfunction. The condition impairs the release of white blood cells from bone marrow into circulation, leading to recurrent and severe infections. Named for its four classic manifestations - warts, hypogammaglobulinemia, infections, and myelokathexis - only a minority of patients experience all four symptoms.
"This positive opinion from the CHMP for mavorixafor represents a key milestone toward making this treatment available to WHIM syndrome (search) patients in the EU," said Adam Craig, M.D., Ph.D., Executive Chairman of X4 Pharmaceuticals. "WHIM syndrome is an ultra-rare disease with a significant unmet medical need."
Strong Clinical Trial Results Support Approval
The CHMP's positive opinion is supported by results from the pivotal Phase 3 clinical trial (4WHIM), a global, randomized, double-blind, placebo-controlled, 52-week multicenter study that evaluated the efficacy and safety of mavorixafor in 31 people aged 12 years and older diagnosed with WHIM syndrome (search).
The trial demonstrated that mavorixafor treatment significantly increased time above threshold (≥500 cells/microliter) for absolute neutrophil count compared to placebo (p<0.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count versus placebo (p<0.0001).
Analysis of individual components of a composite endpoint showed approximately 40% reduction in total infection score, weighted by infection severity, in mavorixafor-treated patients compared with placebo-treated patients. Treatment also resulted in a 60% reduction in the annualized infection rate compared with placebo-treated patients.
Safety Profile and Administration
The most common adverse reactions reported in the 4WHIM trial (≥10% and more frequently reported than placebo) were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness. There was no difference in total wart change scores between the mavorixafor and placebo treatment arms over the 52-week period.
Mavorixafor is a selective CXC chemokine receptor 4 (CXCR4 (search)) antagonist that binds to the CXCR4 receptor, preventing its interaction with CXCL12. The therapy is administered as an oral, once-daily treatment and is currently approved in the United States under the trade name XOLREMDI (search)® for WHIM syndrome (search) treatment.
Commercial Partnership for European Launch
Norgine and X4 Pharmaceuticals entered into a licensing and supply agreement in January 2025, under which Norgine will commercialize mavorixafor in Europe, Australia and New Zealand following regulatory approval. Under the agreement terms, X4 will receive up to €226 million contingent upon achieving certain regulatory and commercial milestones, plus escalating double-digit royalties of up to the mid-twenties on future net sales in licensed territories.
"At Norgine, we have built deep expertise in delivering rare and specialty medicines across Europe, Australia and New Zealand and the positive CHMP opinion for mavorixafor reflects the type of innovation our organisation is designed to bring to patients in need," said Janneke van der Kamp, Chief Executive Officer, Norgine.
All marketing authorizations in the licensed territories will be transferred to Norgine, which will assume responsibility for all market access and commercialization activities. X4 will continue to manufacture and supply mavorixafor to Norgine under the partnership arrangement.