X4 Pharmaceuticals Announces EMA Validation of Marketing Authorization Application (MAA) for Mavorixafor for the Treatment of WHIM Syndrome
X4 Pharmaceuticals , 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 ≥10% patients and more frequently reported than placebo) were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.
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.
Contact
Daniel Ferry
LifeSci Advisors
daniel@lifesciadvisors.com
(617) 430-7576