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Patients with primary chronic neutropenia haven't had a new approved therapy in over 30 years — but that could change. The phase 3 4WARD trial is evaluating mavorixafor, an oral CXCR4 antagonist, against placebo on top of standard therapy. Phase 2 data showed 2–3× increases in neutrophil counts and allowed many patients to reduce or stop G-CSF injections.
For patients with primary chronic neutropenia, injectable G-CSF has been the only FDA-approved treatment for roughly 30 years — and it comes with real downsides like bone pain, splenomegaly, and long-term risks of myelodysplastic syndrome. Now, the phase 3 4WARD trial is testing whether mavorixafor (Xolremdi), an oral once-daily CXCR4 antagonist, can change that. By blocking the signal that keeps neutrophils trapped in the bone marrow, the drug encourages them to circulate into the bloodstream — a fundamentally different mechanism from G-CSF.
Phase 2 results, presented at the 2025 EHA Congress, were encouraging: patients on mavorixafor monotherapy saw mean neutrophil count fold changes of up to 2.6× over 6 months, and those with severe baseline neutropenia saw even greater gains. In the combination cohort, 9 of 12 patients were able to reduce their G-CSF dose, with 3 stopping it entirely. Side effects were mostly mild GI issues early in treatment.
By the Numbers:
Why it matters: If the 4WARD trial succeeds, mavorixafor could become the first new approved therapy for chronic neutropenia in three decades — offering patients an oral alternative to injections with a distinct mechanism and potentially fewer long-term risks.
