X4 Pharmaceuticals Receives Positive Opinion from the EMA CHMP Recommending Approval of Mavorixafor in the EU for WHIM Syndrome
Rhea-AI Summary
X4 Pharmaceuticals (Nasdaq: XFOR) announced the EMA CHMP has issued a positive opinion recommending marketing authorization under exceptional circumstances for mavorixafor (XOLREMDI) to treat WHIM syndrome in the EU. The European Commission is expected to issue a final decision in Q2 2026.
CHMP support is based on the Phase 3 4WHIM trial showing statistically significant increases in ANC and ALC thresholds, ~40% reduction in total infection score, and a 60% reduction in annualized infection rate versus placebo. X4 has a commercialization license with Norgine and may receive up to €226 million plus escalating royalties.
Positive
- CHMP positive opinion recommending EU approval
- Potential first therapy for WHIM syndrome in the EU
- 4WHIM: 60% reduction in annualized infection rate
- License deal: up to €226M plus mid‑twenties royalties
Negative
- Embryo‑fetal toxicity warning for XOLREMDI
- QTc interval prolongation risk requiring monitoring
- Common adverse reactions include thrombocytopenia and rash
Key Figures
Market Reality Check
Peers on Argus
While XFOR fell -5.52%, several biotech peers also traded lower (e.g., IGMS -2.31%, IMMX -2.19%, ACET -1.74%, VANI -0.79%), with IMUX up 2.56%. Mixed peer moves and a scanner flag of false for sector momentum point to a stock‑specific reaction.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Feb 03 | Conference participation | Neutral | +0.5% | Management participation in Guggenheim Emerging Outlook Biotech Summit and investor meetings. |
| Feb 02 | Equity incentives | Neutral | +0.5% | Inducement stock option grants to new employees under 2019 Inducement Equity Plan. |
| Nov 05 | Conference participation | Neutral | -1.3% | Participation in Guggenheim Healthcare Innovation Conference with fireside chat and 1x1s. |
| Nov 05 | Earnings & update | Negative | -10.6% | Q3 2025 loss, large financings, workforce reduction, and focus on 4WARD Phase 3 trial. |
| Oct 27 | Public offering | Negative | +1.9% | Dilutive underwritten equity offering raising about $155.3M and increasing shares outstanding. |
Recent XFOR news has mostly seen price moves align with the underlying tone, with only the October 2025 offering showing a positive price reaction to dilutive financing.
Over the last six months, XFOR’s key events have centered on financing, corporate updates, and investor outreach. An October 2025 public offering raised about $155.3M, followed by Q3 2025 results highlighting $1.6M in net product sales of XOLREMDI, a net loss of $29.8M, major financings totaling $240.3M, and a 50% workforce reduction. More recently, activity has been limited to conference participation and inducement grants with modest price responses, making today’s EU CHMP opinion a more material clinical/regulatory milestone versus that backdrop.
Regulatory & Risk Context
X4 has an active Form S-3 shelf filed on 2025-09-10 covering resale of shares by selling stockholders. The prospectus highlights prior FDA approval of mavorixafor (XOLREMDI) for WHIM syndrome, a 1‑for‑30 reverse split, going‑concern language in the auditor’s report, and extensive pre‑funded warrants with beneficial ownership limits. The shelf has seen at least 2 424B5 takedowns but no total capacity is disclosed here.
Market Pulse Summary
This announcement highlights a positive CHMP opinion recommending marketing authorization of mavorixafor for WHIM syndrome in the EU, backed by the pivotal 4WHIM Phase 3 trial in 31 patients over 52 weeks. Data showed a roughly 40% reduction in infection score and 60% reduction in annualized infection rate versus placebo. The news builds on prior FDA approval in the U.S. and a Norgine partnership with up to €226M in milestones, while an active Form S-3 and past equity financings remain part of the strategic backdrop.
Key Terms
primary immunodeficiency medical
phase 3 medical
randomized, double-blind, placebo-controlled medical
absolute neutrophil count medical
AI-generated analysis. Not financial advice.
- Potential First and Only Therapy in the EU for Ultra-Rare Immune Disorder -
BOSTON, Feb. 27, 2026 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company focused on improving the lives of people with rare hematology diseases, today announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of marketing authorization, under exceptional circumstances, of mavorixafor for the treatment of WHIM syndrome in the European Union (EU). The positive opinion will now be reviewed by the European Commission (EC) with a final approval decision anticipated in the second quarter of 2026.
“This positive opinion from the CHMP for mavorixafor represents a key milestone toward making this treatment available to WHIM syndrome 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. We look forward to the EC's decision and to working with Norgine, our commercial partner in Europe, Australia and New Zealand, to ensure patient access upon a potential approval to the first and only therapy in Europe to treat this devastating condition.”
WHIM syndrome is an ultra-rare, inherited primary immunodeficiency named for its four classic manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis. WHIM is caused by CXCR4 receptor dysfunction that results in impaired mobilization of white blood cells from the bone marrow into peripheral circulation resulting in serious and/or frequent infections.
Mavorixafor, a CXC chemokine receptor 4 antagonist, has been approved by the U.S. Food and Drug Administration (FDA) under the trade name XOLREMDI®, for use as an oral, once-daily therapy in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. XOLREMDI is the first drug ever approved in the United States to treat WHIM syndrome.
The CHMP’s positive opinion for mavorixafor 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 XOLREMDI in 31 people aged 12 years and older diagnosed with WHIM syndrome. The efficacy of XOLREMDI was determined by improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections. In the 4WHIM trial, XOLREMDI treatment demonstrated increased time above threshold (≥500 cells/microliter) for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count (TAT-ALC) v. placebo (p<0.0001). The efficacy of XOLREMDI was further assessed in a composite endpoint consisting of total infection score and total wart change score using a Win-Ratio method. Analyses of the individual components of this composite endpoint showed an approximate
In January 2025, X4 entered into a licensing and supply agreement with Norgine , a European specialist pharmaceutical company, under which Norgine will commercialize mavorixafor in Europe, Australia and New Zealand following regulatory approvals. Under the terms of the license and supply agreement, X4 will receive up to
IMPORTANT SAFETY INFORMATION
CONTRAINDICATION
XOLREMDI® is contraindicated with drugs highly dependent on CYP2D6 for clearance.
WARNINGS AND PRECAUTIONS
- Embryo-Fetal Toxicity: Based on its mechanism of action, XOLREMDI is expected to cause fetal harm when administered to a pregnant woman. Verify pregnancy status of female patients of reproductive potential prior to starting XOLREMDI. Advise females of reproductive potential to use effective contraception during treatment with XOLREMDI and for three weeks after the final dose.
- QTc Interval Prolongation: XOLREMDI causes concentration-dependent QTc prolongation. QTc prolongation may occur when XOLREMDI is taken with concomitant medications that increase XOLREMDI exposure and/or drug products with a known potential to prolong QTc. Correct any modifiable risk factors for QTc prolongation, assess QTc at baseline, and monitor QTc during treatment as clinically indicated in patients with risk factors for QTc prolongation or receiving concomitant medications that increase XOLREMDI exposure and/or drugs with a known potential to prolong the QTc interval. Dose reduction or discontinuation of XOLREMDI may be required.
ADVERSE REACTIONS
The most common adverse reactions (in ≥
DRUG-DRUG INTERACTIONS
Avoid co-administration of XOLREMDI and strong CYP3A4 inducers. Reduce XOLREMDI daily dosage when administered with strong CYP3A4 inhibitors. Monitor more frequently for adverse reactions associated with an increase in exposure of XOLREMDI when used concomitantly with moderate CYP3A4 inhibitors or P-gp inhibitors and reduce XOLREMDI daily dosage if necessary.
USE IN SPECIFIC POPULATIONS
- Advise females that breastfeeding is not recommended during treatment with XOLREMDI and for three weeks after the final dose.
- The safety and effectiveness of XOLREMDI have not been established in pediatric patients younger than 12 years of age.
- XOLREMDI is not recommended in patients with severe renal impairment, end-stage renal disease, or moderate to severe hepatic impairment.
To report suspected adverse reactions, contact X4 Pharmaceuticals at 1-866-MED-X4MI (1-866-633-9464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for XOLREMDI.
About WHIM Syndrome
WHIM syndrome is an ultra-rare, inherited, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 receptor dysfunction that results in impaired mobilization of white blood cells from the bone marrow into peripheral circulation. WHIM syndrome is named for its four classic manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, although only a minority of patients experience all four manifestations. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience serious and/or frequent infections.
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 potential for and the timing of a positive final approval decision from the European Commission (EC) regarding mavorixafor in WHIM syndrome, the potential achievement of milestones and receipt of royalties under the Company’s licensing and supply agreement with Norgine Pharma and other 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 the EC does not provide a positive final approval decision with regard to mavorixafor in WHIM syndrome; that even if approved, mavorixafor may not ultimately be commercially successful; ; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s most recent Annual Report on X4’s 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.
Source: X4 Pharmaceuticals, Inc.
X4 Investor Contact: Remy Bernarda Jenny Kobin IR Advisory Solutions ir@x4pharma.com
FAQ
What did the EMA CHMP recommend for X4 Pharmaceuticals (XFOR) on February 27, 2026?
How did the Phase 3 4WHIM trial support X4's mavorixafor approval for WHIM syndrome (XFOR)?
If approved, will mavorixafor be the first WHIM syndrome therapy in Europe (XFOR)?
What safety risks should investors note about XOLREMDI (XFOR) from the announcement?
What commercial terms did X4 disclose with Norgine for mavorixafor (XFOR)?
