X4 Pharmaceuticals Targets 2028 Phase III Data for Mavorixafor in Chronic Neutropenia

Key Points

• X4 Pharmaceuticals expects to complete enrollment in its pivotal Phase III 4WARD trial of mavorixafor for primary chronic neutropenia by late 2026, with top-line results expected in the first quarter of 2028 and potential FDA approval in late 2028 or early 2029.
• The 126-patient trial will evaluate whether once-daily oral mavorixafor improves absolute neutrophil counts and reduces annualized infections, both as a standalone treatment and alongside G-CSF. X4 reported no new safety signals in blinded data so far.
• X4 estimates an initial U.S. commercial opportunity of about 15,000 patients, potentially expanding to 30,000 depending on the eventual label. The company also plans a 2027 Phase II study testing whether mavorixafor can reduce or eliminate patients’ reliance on G-CSF injections.

X4 Pharmaceuticals NASDAQ: XFOR said it expects to complete enrollment in its pivotal Phase III 4WARD trial of mavorixafor for primary chronic neutropenia, or PCN, by the end of the fourth quarter of 2026, with top-line data anticipated in the first quarter of 2028.

Executive Chairman Adam Craig said positive results could support a potential U.S. Food and Drug Administration approval in late 2028 or early 2029. The company also said it has cash runway into 2029 and is focusing its spending on clinical development.

Mavorixafor is a once-daily oral CXCR4 antagonist intended to increase circulating neutrophils and lymphocytes by mobilizing white blood cells from the bone marrow into the bloodstream. X4 is evaluating the therapy as a monotherapy and in combination with granulocyte colony-stimulating factor, or G-CSF, injections.

Phase III 4WARD trial enrollment and endpoints

John Volpone, X4’s president and chief operating officer, said the global, double-blind, placebo-controlled 4WARD study is designed to enroll 126 patients with congenital, autoimmune or idiopathic chronic neutropenia. Eligible participants must have an absolute neutrophil count, or ANC, below 1,000 cells per microliter and at least two infections requiring intervention during the prior 12 months.

Participants are randomized equally to mavorixafor or placebo, with or without G-CSF. The co-primary endpoints are ANC response, defined as an ANC above 500 cells per microliter, and annualized infection rate. X4 said the study is powered at 93% for the ANC endpoint and 89% for the infection-rate endpoint in the intent-to-treat population.

Based on blinded pooled data from September 2026, the median participant age was 36, 70% of participants were female, and median baseline ANC was 483 cells per microliter. X4 said 68% of participants had experienced at least three infections at baseline, while 37% were receiving concurrent G-CSF. Volpone said the company had not observed new safety signals to date.

During the question-and-answer session, Volpone said the infection endpoint is powered to identify a 30% improvement in annualized infection rate for mavorixafor versus placebo. He said the company believes blinded data are tracking toward that planned reduction or better, while cautioning that the trial remains blinded.

Planned 4STEPS study targets reduced G-CSF use

X4 also introduced 4STEPS, a planned single-arm, open-label Phase II study evaluating whether patients can safely reduce G-CSF use after beginning mavorixafor. The company expects to enroll the first participant in the first quarter of 2027 and report top-line results alongside 4WARD data in the first quarter of 2028.

The trial is expected to enroll about 25 patients with acquired autoimmune or idiopathic PCN who are on stable G-CSF and have baseline ANC of at least 1,000 cells per microliter. After an observation period and an eight-week mavorixafor run-in, patients may reduce G-CSF doses in steps of 25%, 50% and 75%, potentially discontinuing G-CSF entirely.

The study’s efficacy measures at six months include the percentage of patients who discontinue G-CSF, the percentage reduction in average daily G-CSF dose, and the percentage achieving a G-CSF reduction of at least 75%.

Company estimates 15,000-patient initial U.S. opportunity

Michael Massello, senior vice president of market strategy and development, said X4’s claims analyses and physician and patient research identified approximately 95,000 U.S. patients aged 12 and older with a primary chronic neutropenia diagnosis in 2025. The company estimated that about 30,000 had ANC below 1,000 cells per microliter and at least one infection, while roughly 15,000 had at least two infections, including emergency-room visits and hospitalizations.

X4 said it expects an initial commercial focus, if mavorixafor is approved, on the approximately 15,000 patients who more closely resemble the 4WARD population. The potential opportunity could extend to 30,000 symptomatic patients depending on the eventual FDA label, according to the company.

Massello said company research found that roughly one-third of symptomatic patients receive G-CSF and about one-half receive antibiotics. He cited challenges including injection fatigue, bone pain, fatigue and inconsistent neutrophil levels associated with G-CSF, while noting that antibiotics do not address underlying neutropenia and may contribute to resistance with long-term use.

X4’s survey research of 100 hematologists found that approximately 90% said they would intend to prescribe mavorixafor after reviewing an assumed approved product profile, Massello said.

Clinicians describe high disease burden

Julia Warren, a pediatric hematologist and physician-scientist at Children’s Hospital of Philadelphia, said chronic neutropenia can cause painful oral ulcers, mucositis, infection fears and substantial strain on children and families. She said G-CSF is currently the only approved treatment approach she uses prophylactically in practice.

Shreyans Gandhi, a consultant hematologist at King’s College Hospital in London, said patients experience significant emotional, employment and social burdens, and that there is a need for additional treatment options beyond G-CSF. Both clinicians said an oral therapy could offer a meaningful alternative if clinical results are positive and the product receives approval.

About X4 Pharmaceuticals (NASDAQ:XFOR)

X4 Pharmaceuticals, Inc is a biotechnology company focused on developing and commercializing therapies for rare diseases caused by disorders of the immune system. The company's research centers on the CXCR4 pathway, which plays a role in the movement and function of immune cells.

X4's lead product, XOLREMDI (mavorixafor), is an oral CXCR4 antagonist approved by the U.S. Food and Drug Administration for use in patients aged 12 and older with WHIM syndrome, a rare primary immunodeficiency disorder.

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