X4 Pharmaceuticals Announces EMA Validation of Marketing Authorization Application (MAA) for Mavorixafor for the Treatment of WHIM Syndrome
X4 Pharmaceuticals (XFOR) announced that its Marketing Authorization Application (MAA) for mavorixafor to treat WHIM syndrome has been validated for review by the European Medicines Agency (EMA). The submission follows the drug's U.S. FDA approval in April 2024 under the brand name XOLREMDI®, an oral, once-daily treatment for patients 12 years and older with WHIM syndrome.
The application is supported by positive results from the global Phase 3 4WHIM clinical trial, which met its primary endpoint and a key secondary endpoint. The trial demonstrated that mavorixafor reduced the rate, severity, and duration of infections in participants and was generally well tolerated with no treatment-related serious adverse events.
If approved, mavorixafor would be the first drug indicated for WHIM syndrome in Europe, targeting an estimated population of 1,000 people. X4 recently announced an exclusive licensing agreement with Norgine to commercialize mavorixafor in Europe, Australia, and New Zealand. A decision on the MAA is expected in the first half of 2026.
X4 Pharmaceuticals (XFOR) ha annunciato che la sua Domanda di Autorizzazione alla Commercializzazione (MAA) per mavorixafor nel trattamento della sindrome WHIM è stata convalidata per la revisione da parte dell'Agenzia Europea dei Medicinali (EMA). La presentazione segue l'approvazione da parte della FDA statunitense del farmaco nel aprile 2024 con il nome commerciale XOLREMDI®, un trattamento orale, da assumere una volta al giorno, per pazienti di 12 anni e oltre affetti da sindrome WHIM.
La domanda è supportata da risultati positivi provenienti dalla sperimentazione clinica globale di Fase 3 4WHIM, che ha raggiunto il suo obiettivo primario e un importante obiettivo secondario. La sperimentazione ha dimostrato che mavorixafor ha ridotto il tasso, la severità e la durata delle infezioni nei partecipanti ed è stato generalmente ben tollerato, senza eventi avversi gravi correlati al trattamento.
Se approvato, mavorixafor sarebbe il primo farmaco indicato per la sindrome WHIM in Europa, mirando a una popolazione stimata di 1.000 persone. X4 ha recentemente annunciato un accordo di licenza esclusiva con Norgine per commercializzare mavorixafor in Europa, Australia e Nuova Zelanda. Una decisione sulla MAA è attesa nella prima metà del 2026.
X4 Pharmaceuticals (XFOR) anunció que su Solicitud de Autorización de Comercialización (MAA) para mavorixafor, destinado al tratamiento del síndrome WHIM, ha sido validada para revisión por parte de la Agencia Europea de Medicamentos (EMA). La presentación sigue la aprobación del medicamento por la FDA de Estados Unidos en abril de 2024 bajo el nombre comercial XOLREMDI®, un tratamiento oral, de una vez al día, para pacientes de 12 años o más con síndrome WHIM.
La solicitud está respaldada por resultados positivos del ensayo clínico global de Fase 3 4WHIM, que alcanzó su objetivo principal y un objetivo secundario clave. El ensayo demostró que mavorixafor redujo la tasa, severidad y duración de las infecciones en los participantes y fue generalmente bien tolerado, sin eventos adversos serios relacionados con el tratamiento.
Si se aprueba, mavorixafor sería el primer medicamento indicado para el síndrome WHIM en Europa, enfocándose en una población estimada de 1.000 personas. X4 anunció recientemente un acuerdo de licencia exclusiva con Norgine para comercializar mavorixafor en Europa, Australia y Nueva Zelanda. Se espera una decisión sobre la MAA en la primera mitad de 2026.
X4 Pharmaceuticals (XFOR)는 WHIM 증후군 치료를 위한 mavorixafor의 마케팅 허가 신청서(MAA)가 유럽 의약청(EMA)의 검토를 위해 유효성이 확인되었다고 발표했습니다. 이 제출은 2024년 4월 XOLREMDI®라는 상표명으로 약물이 미국 FDA의 승인을 받은 이후 이루어진 것입니다. 이는 WHIM 증후군 환자 12세 이상을 위한 하루 한 번 복용하는 경구 치료제입니다.
이 신청은 글로벌 3상 임상시험인 4WHIM의 긍정적인 결과에 의해 뒷받침되며, 주요 목표 및 주요 이차 목표를 달성했습니다. 이 시험은 mavorixafor가 참가자들의 감염 비율, 중증도 및 지속 시간을 줄였으며, 일반적으로 잘 견딜 수 있었고 치료와 관련된 심각한 부작용이 없음을 입증했습니다.
승인될 경우, mavorixafor는 WHIM 증후군에 대한 첫 번째 약물이 되어 유럽에서 약 1,000명의 인구를 대상으로 하게 됩니다. X4는 최근 Norgine과 mavorixafor를 유럽, 호주 및 뉴질랜드에서 상용화하기 위한 독점 라이센스 계약을 발표했습니다. MAA에 대한 결정은 2026년 상반기에 예상됩니다.
X4 Pharmaceuticals (XFOR) a annoncé que sa Demande d'Autorisation de Mise sur le Marché (MAA) pour mavorixafor dans le traitement du syndrome WHIM a été validée pour examen par l'Agence Européenne des Médicaments (EMA). Cette soumission fait suite à l'approbation par la FDA américaine du médicament en avril 2024 sous le nom de marque XOLREMDI®, un traitement oral à prendre une fois par jour pour les patients de 12 ans et plus atteints du syndrome WHIM.
La demande est soutenue par des résultats positifs issus de l'essai clinique mondial de Phase 3 4WHIM, qui a atteint son objectif principal et un objectif secondaire clé. L'essai a démontré que mavorixafor réduisait le taux, la gravité et la durée des infections chez les participants et était généralement bien toléré, sans événements indésirables graves liés au traitement.
Si approuvé, mavorixafor serait le premier médicament indiqué pour le syndrome WHIM en Europe, ciblant une population estimée à 1 000 personnes. X4 a récemment annoncé un accord de licence exclusif avec Norgine pour commercialiser mavorixafor en Europe, en Australie et en Nouvelle-Zélande. Une décision concernant la MAA est attendue dans la première moitié de 2026.
X4 Pharmaceuticals (XFOR) gab bekannt, dass der Antrag auf Genehmigung des Inverkehrbringens (MAA) für mavorixafor zur Behandlung des WHIM-Syndroms von der Europäischen Arzneimittel-Agentur (EMA) zur Prüfung validiert wurde. Die Einreichung folgt der Genehmigung des Medikaments durch die US-FDA im April 2024 unter dem Markennamen XOLREMDI®, einer oral verabreichten, einmal täglichen Behandlung für Patienten ab 12 Jahren mit WHIM-Syndrom.
Der Antrag wird durch positive Ergebnisse aus der globalen Phase-3-Studie 4WHIM unterstützt, die ihr primäres Ziel sowie ein wichtiges sekundäres Ziel erreicht hat. Die Studie zeigte, dass mavorixafor die Rate, Schwere und Dauer von Infektionen bei den Teilnehmern reduzierte und im Allgemeinen gut vertragen wurde, ohne schwerwiegende nebenwirkungen, die mit der Behandlung in Zusammenhang standen.
Wenn genehmigt, wäre mavorixafor das erste Medikament, das in Europa für das WHIM-Syndrom zugelassen ist, und richtet sich an eine geschätzte Population von 1.000 Menschen. X4 hat kürzlich eine exklusive Lizenzvereinbarung mit Norgine zur Vermarktung von mavorixafor in Europa, Australien und Neuseeland angekündigt. Eine Entscheidung über den MAA wird im ersten Halbjahr 2026 erwartet.
- FDA approval already secured in April 2024 for patients 12 years and older
- Successful Phase 3 trial meeting primary and key secondary endpoints
- No treatment-related serious adverse events reported in clinical trials
- First potential drug for WHIM syndrome in Europe (estimated 1,000 patient market)
- Strategic partnership with Norgine for commercialization in Europe, Australia, and New Zealand
- EMA decision not expected until 1H 2026
- to patients 12 years and older
- Safety concerns including QTc interval prolongation risk
- Multiple drug interaction restrictions and contraindications
Insights
The EMA validation of mavorixafor's MAA marks a crucial milestone for X4 Pharmaceuticals' European expansion strategy. With an estimated 1,000 WHIM syndrome patients in Europe, this represents a significant market opportunity for the first potential approved therapy in this region. The recent Norgine partnership strategically positions X4 for successful commercialization, leveraging Norgine's established European infrastructure and reducing X4's commercial investment requirements.
The timing of the expected EMA decision in 1H 2026 aligns well with the company's commercial preparation timeline. The successful U.S. launch of XOLREMDI in 2024 provides valuable real-world experience and data that could support European market access negotiations. The positive Phase 3 trial results, particularly the achievement of both primary and key secondary endpoints with a favorable safety profile, strengthen the probability of EMA approval.
The strategic decision to partner with Norgine for European commercialization demonstrates prudent resource management, allowing X4 to focus on the U.S. market while maintaining exposure to European market potential through the partnership agreement. This dual-market strategy could provide diversified revenue streams and reduce commercial risks.
The validation of mavorixafor's MAA represents a significant market opportunity in the rare disease space. As the first potential treatment for WHIM syndrome in Europe, mavorixafor could command premium pricing typical of orphan drugs. The estimated European patient population of 1,000 individuals represents a meaningful revenue opportunity, particularly given the chronic nature of WHIM syndrome requiring long-term treatment.
The partnership with Norgine is strategically sound, as European market access requires specialized expertise in navigating different national healthcare systems and reimbursement processes. Norgine's established presence and experience in rare diseases could accelerate market penetration and optimize pricing strategies across different European markets.
The absence of approved treatments for WHIM syndrome in Europe positions mavorixafor favorably from a pricing and market access perspective. The demonstrated clinical benefits in reducing infection rates and improving key blood cell counts provide strong health economic arguments for reimbursement discussions with European payers.
Submission supported by positive results from global, Phase 3 4WHIM clinical trial;
U.S. regulatory approval in WHIM syndrome granted in 2024
Decision on MAA expected in 1H 2026
BOSTON, Jan. 24, 2025 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that its Marketing Authorization Application (MAA) for mavorixafor for the treatment of WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis), a rare primary immunodeficiency, has been validated for review and is now under evaluation with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The EMA previously granted orphan designation to mavorixafor in WHIM syndrome. In April 2024, mavorixafor received U.S. Food and Drug Administration approval as XOLREMDI®, an oral, once-daily treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes.
“Making mavorixafor available to those in the European Union living with WHIM syndrome is a top priority for X4 and this submission demonstrates our continued ability to deliver on our key milestones and generate growth,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “With our MAA now validated for review by the EMA, we expect to enable our recently announced European partner, Norgine, to provide this much-needed treatment to patients as rapidly as possible should it be approved. We look forward to working alongside the EMA as they assess our application.”
Mavorixafor is a small-molecule antagonist of the CXCR4 receptor being developed as a once-daily oral therapy for people with rare primary immunodeficiencies, including WHIM syndrome. The global, pivotal, 4WHIM Phase 3 trial that X4 conducted met its primary endpoint, a key secondary endpoint, and was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events. Additionally, in the 4WHIM trial, once-daily oral mavorixafor resulted in reductions in the rate, severity, and duration of infections in participants with WHIM syndrome.
If approved by the EMA, mavorixafor would be the first drug indicated for patients with WHIM syndrome in Europe, a population estimated to be approximately 1,000 people. Earlier this month X4 announced an exclusive licensing and supply agreement with Norgine to commercialize mavorixafor in Europe, Australia, and New Zealand.
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 a rare, 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 in the acronym. 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. It is estimated that at least 1,000 people are currently diagnosed with WHIM syndrome in the U.S., with another 1,000 estimated in Europe.
About XOLREMDI® (mavorixafor)
XOLREMDI (mavorixafor) is a selective CXCR4 receptor antagonist approved in the U.S. as an oral, once-daily treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. CXCR4 receptor stimulation by its ligand, CXCL12, has been shown to play a key role in the movement of white blood cells (leukocytes) to and from the bone marrow compartment. Treatment with XOLREMDI results in increased mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation.
About X4 Pharmaceuticals
X4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging expertise in CXCR4 and immune system biology, X4 has successfully developed mavorixafor, an orally available CXCR4 antagonist that is currently being marketed in the U.S. as XOLREMDI
in its first indication and being reviewed by the EMA for approval in the EU for the same indication. The company is also evaluating additional uses of mavorixafor and is conducting a global, pivotal Phase 3 clinical trial (4WARD) in people with certain chronic neutropenic disorders. X4 is headquartered in Boston, Massachusetts and operates a research center of excellence in Vienna, Austria. For more information, please visit www.x4pharma.com.
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 X4’s expectations related to the EMA’s evaluation of mavorixafor for WHIM syndrome; the potential for MAA approval in the European Union; X4’s plans to work with its partner, Norgine, to broaden patient access; the initiation, timing, progress, and results of X4’s current and future preclinical studies and clinical trials and related preparatory work and the period during which the results of trials will become available, as well as X4’s research and development programs; the timing and anticipated interactions with regulatory authorities and any related approvals for mavorixafor in Europe, Australia, and New Zealand, including a marketing authorization application; the potential market opportunity for mavorixafor; the anticipated strategic benefits of X4’s exclusive licensing agreement with Norgine and of any current or future collaborations; and the mission and goals for X4’s business. 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: uncertainties inherent in the regulatory approval process could impact the timing, progress, and outcome of the EMA’s review; potential delays or difficulties in commercializing mavorixafor in Europe could occur even if regulatory approval is granted; there could be challenges in coordinating with external partners including Norgine; X4 may have difficulty establishing and maintaining an effective sales and marketing organization or suitable third-party alternatives for any approved products; X4 may not be able to obtain or maintain orphan drug designation or exclusivity for X4’s drug candidates, which could limit the potential profitability of X4’s product candidates; X4 may not be able to obtain regulatory approval for, or successfully commercialize, mavorixafor or any other product candidate for other chronic neutropenic disorders or any other potential indication; the expected availability, content, and timing of clinical data from X4’s ongoing clinical trials of mavorixafor may be delayed or unavailable, including X4’s ongoing Phase 3 clinical trial; the design and rate of enrollment for clinical trials, including the current design of a Phase 3 clinical trial evaluating mavorixafor in certain chronic neutropenic disorders may not enable successful completion of the trial(s); the commercial opportunity for mavorixafor in chronic neutropenic disorders may be smaller than anticipated; X4 may be unable to obtain and maintain regulatory approvals, including the marketing authorization approval; uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development; the regulatory review and approval processes of the FDA, EMA, and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if X4 is ultimately unable to obtain regulatory approval for X4’s product candidates, including additional indications for mavorixafor, X4’s business will be substantially harmed; initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials, including assessing the ability of mavorixafor monotherapy to durably increase absolute neutrophil count in patients with chronic neutropenia; adverse safety effects could arise from the testing or use of X4’s product and product candidates; the need to align with X4’s collaborators may hamper or delay X4’s development and commercialization efforts or increase X4’s costs; X4’s business may be adversely affected and costs may increase if any of X4’s key collaborators fails to perform its obligations or terminates the collaboration; the internal and external costs required for X4’s ongoing and planned activities, and the resulting impact on expense and use of cash, may be higher than expected, which may cause the company to use cash more quickly than expected or to change or curtail some of X4’s plans or both; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s Quarterly Report on X4’s Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 13, 2024, and in other filings X4 makes with the SEC 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.
Investor Contact:
Daniel Ferry
LifeSci Advisors
daniel@lifesciadvisors.com
(617) 430-7576
Media Contact:
Rhiannon Jeselonis
Ten Bridge Communications
rhiannon@tenbridgecommunications.com
FAQ
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