X4 Pharmaceuticals Announces Positive Outcome from FDA Type C Meeting
FDA alignment on a smaller 4WARD Phase 3 trial design may accelerate X4’s mavorixafor path toward a potential sNDA in chronic neutropenia.
Rhea-AI Summary
X4 Pharmaceuticals (XFOR) reports a positive outcome from an FDA Type C Meeting on its global 4WARD Phase 3 chronic neutropenia trial. The FDA agreed that reducing the trial sample size from 176 to 126 participants maintains adequate statistical power for the co-primary endpoints of annualized infection rate reduction and positive absolute neutrophil count (ANC) response. The agency also indicated that the proposed safety database would be acceptable to support a potential supplemental new drug application (sNDA) for mavorixafor in chronic neutropenia.
X4 expects to complete enrollment in 4WARD by year-end 2026 and to report topline data in the first half of 2028. The 52-week, randomized, double-blind, placebo-controlled, multicenter trial will enroll 126 patients aged 12 and older with chronic neutropenia and recurrent and/or serious infections. Mavorixafor, an oral CXCR4 antagonist already marketed in the U.S. as XOLREMDI in another indication, has Fast Track designation from the FDA for treating chronic neutropenia.
Positive
- 4WARD sample size cut from 176 to 126 patients with FDA concurrence while maintaining stated power for co-primary endpoints
- FDA indicated the proposed safety database is acceptable to support a potential sNDA for mavorixafor in chronic neutropenia
- Company targets 4WARD enrollment completion by year-end 2026 and topline data readout in H1 2028
- 4WARD is a global, pivotal Phase 3, randomized, double-blind, placebo-controlled trial over 52 weeks in 126 patients
- Mavorixafor is commercially available in the U.S. as XOLREMDI in its first indication
- Mavorixafor has FDA Fast Track designation for the treatment of chronic neutropenia
Negative
- None.
Key Figures
- Trial sample size
- 126 participants
- Reduced from 176 participants for the Phase 3 4WARD trial
- Enrollment deadline
- Year-end 2026
- Expected completion of 4WARD enrollment
- Topline data timing
- H1 2028
- Expected 4WARD topline data
- Trial duration
- 52 weeks
- 4WARD Phase 3 trial
- Baseline ANC threshold
- <1,000 cells per microliter
- Confirmed trough ANC at baseline screening
- Prior infection history
- 2 or more serious and/or recurrent infections
- Required during the prior year for trial enrollment
Historical Context
-
Q2 update cited 4WARD progress and a planned FDA meeting on sample size.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
sNDA regulatory
absolute neutrophil count (ANC) medical
CRO technical
fast track designation regulatory
AI-generated analysis. How Rhea-AI works. Not financial advice.
- FDA Agrees to Reduced Sample Size for the Global 4WARD Phase 3 Chronic Neutropenia Trial -
- Expect Completion of Enrollment by Year-End 2026 and Topline Data in H1 2028 -
BOSTON, Sept. 08, 2026 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company focused on improving the lives of people with rare hematology diseases, today announced the positive outcome of its Type C Meeting with the U.S. Food and Drug Administration (FDA) related to the global 4WARD Phase 3 clinical trial. The purpose of the meeting was to gain alignment on a revised sample size and associated statistical power and the size of the safety database to support a supplemental new drug application (sNDA) for mavorixafor for the treatment of chronic neutropenia in 4WARD.
The FDA agreed with the Company’s analysis that the reduction in sample size for the 4WARD trial from 176 to 126 participants maintains adequate overall power for the co-primary endpoints of the reduction in annualized infection rate and positive absolute neutrophil count (ANC) response. In addition, the FDA indicated that the proposed safety database would be acceptable to support a potential sNDA.
“After a rigorous re-examination of the statistical plan for 4WARD, we determined that the trial was overpowered and that we could reduce the sample size to 126 participants while preserving good statistical power for our co-primary endpoints,” said Adam Craig, M.D., Ph.D., Executive Chairman of X4 Pharmaceuticals. “We are pleased that the FDA agreed with our analysis. With continued execution from our new Clinical Research Organization (CRO), we expect to complete the enrollment of 4WARD by the end of this year and report topline data in the first half of 2028.”
“With an estimated 15,000 patients experiencing serious and/or recurring infections as a result of their chronic neutropenia, we continue to believe mavorixafor can address a significant market opportunity based on its unique value proposition for the treatment of this rare disease with very limited therapy options,” concluded Dr. Craig.
About the 4WARD Clinical Trial
The 4WARD trial is a global, pivotal Phase 3 clinical trial evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in patients with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 126 patients aged 12 years and older with confirmed trough absolute neutrophil count (ANC) levels less than 1,000 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The co-primary endpoints of the study are the reduction in annualized infection rate and positive absolute neutrophil count (ANC) response. For more information, visit clinicaltrials.gov (NCT06056297).
About Chronic Neutropenia and Mavorixafor
Chronic neutropenia is a primary, rare blood condition characterized by abnormally low levels of circulating neutrophils in the blood lasting more than three months, persistently or intermittently. As a result, people with chronic neutropenia are at an increased risk of serious and life-threatening infections and reduced quality of life. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells. Mavorixafor is a small molecule delivered in a capsule for oral dosing as a selective antagonist of the chemokine receptor, CXCR4. Down-regulation of the CXCR4 receptor by mavorixafor has been shown to mobilize functional neutrophils from the bone marrow into the peripheral bloodstream across multiple disease states. The level of circulating neutrophils is typically determined by the absolute neutrophil count (ANC) obtained from a blood draw.
About X4 Pharmaceuticals
X4 Pharmaceuticals is a company focused on improving the lives of people with rare hematology diseases by developing and commercializing innovative therapies in areas with significant unmet needs. Leveraging expertise in diseases of the immune system and CXCR4 biology, X4 has successfully developed mavorixafor, an orally available CXCR4 antagonist that is commercially available in the U.S. as XOLREMDI® in its first indication. The Company is currently conducting a global, pivotal Phase 3 clinical trial (4WARD) evaluating mavorixafor in chronic neutropenic disorders. The U.S. FDA has granted Fast Track designation to mavorixafor for the treatment of chronic neutropenia. X4 is headquartered in Boston, Massachusetts. For more information, please visit www.x4pharma.com.
X4 Forward Looking Statements
This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target,” or other similar terms or expressions that concern X4’s expectations, strategy, plans, or intentions. Forward-looking statements include, without limitation, implied or express statements regarding the Company’s ability to obtain and maintain regulatory approval for its product candidates, plans for the commercialization of XOLREMDI in the European Union by Norgine, the potential achievement of milestones and receipt of royalties under the Company’s licensing and supply agreement with Norgine, the expected design and enrollment of the Company’s clinical trials, including expected timing for full enrollment in 4WARD, the sufficiency of the Company’s cash resources and its expected cash runway, and future plans for the Company. Any forward-looking statements in this press release are based on management’s current expectations and beliefs. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond X4’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risks that even if approved, mavorixafor may not ultimately be commercially successful; the Company is unable to initiate and complete its clinical trials, including the 4WARD trial; the FDA’s feedback provided in connection with the Type C meeting is not binding on the FDA and the FDA may take a different position in connection with its review of any sNDA; the reduced sample size may adversely affect the ability of the 4WARD trial to demonstrate statistically significant results with respect to its co-primary endpoints; enrollment in the 4WARD trial may not be completed within the timeframe described in this press release, or at all; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s most recent Annual Report on Form 10-K, as well as in other filings X4 makes with the Securities and Exchange Commission, including its Quarterly Reports on Form 10-Q, from time to time. X4 undertakes no obligation to update the information contained in this press release to reflect new events or circumstances, except as required by law.
X4 Investor Contact:
Remy Bernarda
Jenny Kobin
IR Advisory Solutions
IR@X4pharma.com
Source: X4 Pharmaceuticals, Inc.
FAQ
What was the purpose of the FDA Type C Meeting for X4 Pharmaceuticals?
The Type C Meeting focused on gaining alignment with the FDA on a revised sample size and associated statistical power for the 4WARD Phase 3 trial, as well as on the size of the safety database needed to support a potential supplemental new drug application (sNDA) for mavorixafor in chronic neutropenia.
What are the co-primary endpoints of the 4WARD Phase 3 chronic neutropenia trial?
The co-primary endpoints of 4WARD are the reduction in annualized infection rate and a positive absolute neutrophil count (ANC) response.
Which patients are eligible for enrollment in the 4WARD trial?
The 4WARD trial aims to enroll 126 patients aged 12 years and older with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who have trough ANC levels below 1,000 cells per microliter at baseline screening and a history of two or more serious and/or recurrent infections in the prior year.
How is the 4WARD trial for mavorixafor in chronic neutropenia designed?
4WARD is a global, pivotal, 52-week Phase 3 study that is randomized, double-blind, placebo-controlled, and multicenter, evaluating the efficacy, safety, and tolerability of once-daily oral mavorixafor, with or without G-CSF, in patients with chronic neutropenia who experience recurrent and/or serious infections.
What is mavorixafor and how does it work in chronic neutropenia?
Mavorixafor is a small-molecule, oral capsule that acts as a selective antagonist of the chemokine receptor CXCR4. By down-regulating CXCR4, it has been shown to mobilize functional neutrophils from the bone marrow into the peripheral bloodstream across multiple disease states, increasing circulating neutrophil levels measured by absolute neutrophil count (ANC).
What regulatory status does mavorixafor have for chronic neutropenia?
The U.S. FDA has granted Fast Track designation to mavorixafor for the treatment of chronic neutropenia, and the FDA indicated that the proposed safety database from 4WARD would be acceptable to support a potential sNDA.