X4 Pharma gets FDA support for smaller 4WARD trial
FDA agreed X4’s 4WARD Phase 3 trial can cut enrollment to 126 patients while keeping power, supporting plans for enrollment completion by late 2026 and topline data in early 2028.
Rhea-AI Filing Summary
X4 Pharmaceuticals, Inc. (XFOR) reports a positive outcome from a Type C Meeting with the U.S. Food and Drug Administration regarding its global 4WARD Phase 3 trial of mavorixafor in chronic neutropenia. The FDA agreed with X4’s analysis to reduce the 4WARD trial sample size from 176 to 126 participants while maintaining adequate overall power for the co-primary endpoints of reduced annualized infection rate and positive absolute neutrophil count (ANC) response. The FDA also indicated that the proposed safety database would be acceptable to support a potential supplemental new drug application (sNDA).
X4 states that, with support from its new clinical research organization, it expects to complete enrollment in 4WARD by the end of 2026 and to report topline data in the first half of 2028. The company highlights an estimated 15,000 patients with serious and/or recurring infections from chronic neutropenia as a potential market and notes that mavorixafor, an oral CXCR4 antagonist already available in the U.S. as XOLREMDI in a first indication, has U.S. FDA Fast Track designation for chronic neutropenia.
Positive
- FDA agreement on reduced sample size from 176 to 126 participants while maintaining adequate power for co-primary endpoints may lower trial burden and cost while keeping the study statistically robust.
- FDA signaled the proposed safety database is acceptable to support a potential sNDA for mavorixafor in chronic neutropenia, clarifying regulatory expectations for approval planning.
- Mavorixafor has U.S. Fast Track designation for chronic neutropenia and targets an estimated 15,000 patients with serious or recurring infections, underscoring a defined rare-disease market opportunity.
Negative
- FDA feedback from the Type C Meeting is not binding, and X4 notes the agency may take a different position when reviewing any future sNDA.
- Reduced sample size creates statistical risk: X4 discloses that cutting enrollment to 126 participants may adversely affect the 4WARD trial’s ability to demonstrate statistically significant results on its co-primary endpoints.
- Key efficacy data are long-dated, with topline Phase 3 results expected in the first half of 2028, extending the timeline before clarity on efficacy in chronic neutropenia.
Filing Explained
The FDA’s Type C meeting feedback is not binding and may not represent the agency’s position when reviewing any future supplemental new drug application.
8-K Event Classification
2 items: 8.01, 9.01
2 items
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, or exhibit attachments filed with this report.
Key Figures
4WARD planned sample size (original): 176 participants
4WARD planned sample size (revised): 126 participants
Estimated chronic neutropenia patients with serious/recurring infections: 15,000 patients
+5 more
8 metrics
4WARD planned sample size (original)
176 participants
Initial target enrollment before FDA-agreed reduction
4WARD planned sample size (revised)
126 participants
FDA agreed this maintains adequate power for co-primary endpoints
Estimated chronic neutropenia patients with serious/recurring infections
15,000 patients
Potential addressable population cited by X4
4WARD trial duration
52 weeks
Length of randomized, double-blind, placebo-controlled treatment period
Baseline ANC threshold
1,000 cells per microliter
Maximum trough absolute neutrophil count at screening for eligibility
Minimum age for participants
12 years
Eligible patients for enrollment in the 4WARD trial
Infection history requirement
2 or more infections in prior year
Serious and/or recurrent infections required for enrollment
Topline data timing
First half of 2028
Company’s expectation for 4WARD Phase 3 topline readout
Key Terms
Type C Meeting, supplemental new drug application (sNDA), absolute neutrophil count (ANC), chronic neutropenia, +2 more
6 terms
Type C Meeting regulatory
"positive outcome of its Type C Meeting with the U.S. Food and Drug Administration"
supplemental new drug application (sNDA) regulatory
"to support a supplemental new drug application (sNDA) for mavorixafor"
A supplemental new drug application (snda) is a formal request made to regulatory authorities to make changes to an already approved medication, such as adding new uses, adjusting dosages, or improving manufacturing processes. It’s similar to updating a product’s packaging or instructions after it has been approved for sale. For investors, an snda signals ongoing development or improvements that could impact a company’s future sales or regulatory approval prospects.
absolute neutrophil count (ANC) medical
"co-primary endpoints of the reduction in annualized infection rate and positive absolute neutrophil count (ANC) response"
Absolute neutrophil count (ANC) is a lab measure of the number of neutrophils, a type of white blood cell that fights infection, present in a cubic millimeter of blood. It matters to investors because ANC levels are a key safety and efficacy marker in drug development and medical treatment: low ANC can signal an increased infection risk that may affect clinical trial outcomes, regulatory reviews, labeling, or marketability.
chronic neutropenia medical
"mavorixafor for the treatment of chronic neutropenia in 4WARD"
A long-lasting medical condition in which the blood has an abnormally low number of neutrophils, a type of white blood cell that acts like the body’s first responders against bacterial and fungal infections. Because it raises the risk of recurrent or severe infections and often requires ongoing monitoring, treatments, or preventive measures, chronic neutropenia is important to investors in healthcare and biotech as it affects clinical trial design, regulatory requirements, market need for therapies, and potential product safety or liability considerations.
CXCR4/CXCL12 axis medical
"Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis"
Fast Track designation regulatory
"The U.S. FDA has granted Fast Track designation to mavorixafor"
Fast track designation is a status the U.S. Food and Drug Administration grants to drugs intended to treat serious conditions and address an unmet medical need. It gives the developer more frequent communication with the FDA and can allow parts of the application to be reviewed on a rolling basis, and it may pave the way to priority review or accelerated approval. It can shorten development timelines, though it does not guarantee approval.
FAQ
What did X4 Pharmaceuticals (XFOR) announce about its 4WARD Phase 3 trial?
X4 announced a positive outcome from an FDA Type C Meeting for the 4WARD Phase 3 chronic neutropenia trial. The FDA agreed the sample size can be reduced from 176 to 126 patients while maintaining adequate power and indicated the proposed safety database is acceptable for a potential sNDA.
How is the 4WARD trial for X4 Pharmaceuticals (XFOR) changing after the FDA meeting?
The 4WARD trial’s planned enrollment is being reduced from 176 to 126 participants. X4 and the FDA agreed this still provides adequate power for the co-primary endpoints of annualized infection rate reduction and positive absolute neutrophil count (ANC) response.
When does X4 Pharmaceuticals (XFOR) expect 4WARD enrollment completion and topline data?
X4 states it expects to complete enrollment in the 4WARD Phase 3 trial by the end of 2026 and to report topline data in the first half of 2028, assuming continued execution with its new clinical research organization.
What indication is X4 targeting with mavorixafor in the 4WARD trial?
The 4WARD trial evaluates oral, once-daily mavorixafor (with or without G-CSF) in patients with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who have recurrent and/or serious infections and low absolute neutrophil counts.
How large is the potential market X4 Pharmaceuticals (XFOR) cites for chronic neutropenia?
X4 cites an estimated 15,000 patients experiencing serious and/or recurring infections due to chronic neutropenia. The company believes mavorixafor’s profile could address this rare-disease population, where current therapy options are described as very limited.
What regulatory designations and risks does X4 Pharmaceuticals (XFOR) highlight for mavorixafor?
X4 notes mavorixafor has U.S. FDA Fast Track designation for chronic neutropenia. It also discloses risks that FDA feedback from the Type C Meeting is not binding and that the reduced sample size could impair the 4WARD trial’s ability to show statistically significant results.
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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CURRENT REPORT
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Date of Report (Date of earliest event reported): September 8, 2026
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
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| Item 8.01. | Other Events. | ||||
On September 8, 2026, X4 Pharmaceuticals, Inc. (the “Company”) issued a press release announcing the positive outcome of the Company’s Type C Meeting with the U.S. Food and Drug Administration related to the global 4WARD Phase 3 clinical trial.
A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.
| Item 9.01. | Financial Statements and Exhibits. | ||||
(d) Exhibits. The following exhibits are being furnished herewith:
| Exhibit Number | Exhibit Title or Description | |||||||
| 99.1 | Press Release, dated September 8, 2026 | |||||||
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| X4 PHARMACEUTICALS, INC. | |||||||||||
| By: | /s/ David Kirske | ||||||||||
| David Kirske | |||||||||||
| Date: September 8, 2026 | Chief Financial Officer and Treasurer | ||||||||||
Exhibit 99.1X4 Pharmaceuticals Announces Positive Outcome from FDA Type C Meeting
- 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, September 8, 2026 – 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.