WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Overview
Mavorixafor is a {{{drugClass}}} that is FDA approved for the treatment of XOLREMDI is a CXC chemokine receptor 4 antagonist that is FDA approved in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.. Common adverse reactions include The most common adverse reactions (›10% and at a frequency higher than placebo) were: thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
XOLREMDI is indicated in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lympocytes.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Mavorixafor in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Mavorixafor in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Mavorixafor FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Mavorixafor in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Mavorixafor in pediatric patients.
Contraindications
Use of XOLREMDI is contraindicated with drugs that are highly dependent on CYP2D6 for clearance.
Warnings
Embryo-Fetal Toxicity:
Based on its mechanism of action, XOLREMDI is expected to cause fetal harm when administered to a pregnant woman. models link reductions in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and to abnormal placental development.
Verify the pregnancy status of female patients of reproductive potential prior to starting XOLREMDI. Advise females of reproductive potential to use an effective method of contraception during treatment with XOLREMDI and for 3 weeks after the final dose.
QTc Interval Prolongation:
XOLREMDI causes concentration-dependent QTc interval prolongation. QTc interval 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 (e.g., hypokalemia), assess QTc at baseline and monitor QTc during treatment as clinically indicated in patients with risk factors for QTc prolongation such as those receiving concomitant medications that increase XOLREMDI exposure and drug products with a known potential to prolong QTc. A dose reduction in XOLREMDI or discontinuation of XOLREMDI may be required
Adverse Reactions
Clinical Trials Experience
QTc Interval Prolongation:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of XOLREMDI was evaluated in Study 1, a randomized placebo-controlled trial of 31 adult and pediatric patients 12 years and older with WHIM syndrome .. Patients received XOLREMDI 400 mg or 200 mg, based on age and body weight (N=14) or placebo (N=17). One patient received the 200 mg dose, and 13 patients received the 400 mg dose. Note that the 200 mg XOLREMDI daily dose is only recommended for use in patients receiving strong CYP3A4 inhibitors. For all other patients, the recommended dosage is either 400 mg daily (if weighing more than 50 kg) or 300 mg daily (if weighing up to 50 kg), unless dose reductions are needed due to concomitant use with moderate CYP3A4 inhibitors or P-gp inhibitors.
The data below are based on the 52-week, placebo-controlled portion of the study. Twelve patients received XOLREMDI for at least 6 months, and 10 patients received XOLREMDI for at least 1 year.
The most common adverse reactions (>10%) in Study 1, which were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness. In Study 1, adverse reactions occurring in ≥10% of patients with WHIM syndrome who received XOLREMDI and were reported more frequently than with placebo included thrombocytopenia (21% with XOLREMDI vs. 0% with placebo), pityriasis (14% vs. 0%), rash (14% vs. 0%), rhinitis (14% vs. 0%), epistaxis (14% vs. 6%), vomiting (14% vs. 6%), and dizziness (14% vs. 6%)
Serious adverse reactions of thrombocytopenia occurred in 3 of the 14 patients who received XOLREMDI, 2 of which occurred in the setting of infection or febrile neutropenia.
Postmarketing Experience
There is limited information regarding Mavorixafor Postmarketing Experience in the drug label.
Drug Interactions
Effect of Other Drugs on XOLREMDI
Strong or Moderate CYP3A4 Inhibitors
Reduce XOLREMDI daily dosage to 200 mg when used concomitantly with a strong CYP3A4 inhibitor. Monitor more frequently for XOLREMDI adverse reactions that may be associated with an increase in mavorixafor exposure when used concomitantly with moderate CYP3A4 inhibitor and reduce the XOLREMDI daily dosage by steps of 100 mg, if necessary, but not to a dose less than 200 mg.Mavorixafor is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases mavorixafor maximal concentrations (C max) and area under the concentration-time curve (AUC), which may increase the risk of XOLREMDI adverse reactions.
Strong CYP3A4 Inducers
Avoid concomitant use with a strong CYP3A4 inducer. Mavorixafor is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inducer is predicted to decrease mavorixafor C maxand AUC based upon a mechanistic understanding of its elimination , which may reduce XOLREMDI's effectiveness.
P-gp Inhibitors
Monitor more frequently for XOLREMDI adverse reactions that may be associated with an increase in mavorixafor exposure when used concomitantly with P-gp inhibitors and reduce the XOLREMDI daily dosage by steps of 100 mg, if necessary, but not to a dose less than 200 mg. Mavorixafor is a P-gp substrate. Concomitant use with a P-gp inhibitors increases mavorixafor C maxand AUC, which may increase the risk of XOLREMDI adverse reactions.
Effect of XOLREMDI on Other Drugs
CYP2D6 Substrates
The use of XOLREMDI with drugs that are another drug highly dependent on CYP2D6 for clearance is contraindicated. Mavorixafor is a CYP2D6 inhibitor. Mavorixafor increases exposure of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates.
CYP3A4 Substrates
Monitor for CYP3A4 substrate related adverse reactions more frequently, unless otherwise recommended in the substrate's Prescribing Information, when XOLREMDI is used concomitantly with CYP3A4 substrates where minimal substrate concentration changes may lead to serious adverse reactions. Mavorixafor is an inhibitor of CYP3A4. Mavorixafor may increase the C maxand AUC of CYP3A4 substrates, which may increase the risk of adverse reactions from the CYP3A4 substrate.
P-gp Substrates
Monitor for P-gp substrate related adverse reactions more frequently, unless otherwise recommended in the substrate's Prescribing Information, when XOLREMDI is used concomitantly with P-gp substrates where minimal substrate concentration changes may lead to serious adverse reactions.
Digoxin: Measure serum digoxin concentrations before initiating concomitant use with XOLREMDI, and continue monitoring serum digoxin concentrations as recommended in the Prescribing Information for digoxin.
Mavorixafor is an inhibitor of P-gp. Mavorixafor may increase the C maxand AUC of P-gp substrates, which may increase the risk of adverse reactions from the P-gp substrate.
Metformin: Monitor for glycemic control and adjust the dose of metformin as necessary. Mavorixafor may decrease the mean C maxand AUC of metformin, which may reduce metformin's effectiveness. The mechanism of this interaction is unknown.
Drugs that Prolong the QTc Interval
Obtain an electrocardiogram when initiating, during concomitant use, and as clinically indicated in patients receiving concomitant medications with a known potential to prolong the QTc interval. XOLREMDI causes QTc interval prolongation.
Concomitant use of XOLREMDI with other products that prolong QTc interval may result in a greater increase in QTc interval and adverse reactions associated with QTc interval prolongation, including torsade de pointes, other serious arrythmias, and sudden death.
Based on its mechanism of action, XOLREMDI is expected to cause fetal harm when administered to a pregnant woman There are no available data on XOLREMDI use in pregnant women informing the risk of embryo-fetal developmental toxicities. Animal models link reductions in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development . No definitive animal studies have been conducted to evaluate the effect of mavorixafor on reproduction and fetal development.
Advise pregnant women of the potential risk to the fetus and to use effective contraception .
The estimated background risk of major birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data: Animal reproduction studies have not been conducted with mavorixafor to evaluate effects on reproduction and embryo-fetal development. CXCR4/SDF-1 signaling plays an important role in mammalian embryo-fetal and placental development. In mice, CXCR4-/- knockout is embryo lethal and causes multiple developmental toxicities, most notably in the hematopoietic, cardiovascular and nervous systems. CXCR4/SDF-1 levels have a key role in stimulating trophoblast proliferation and differentiation necessary for appropriate placental growth and function in humans.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mavorixafor in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Mavorixafor during labor and delivery.
Nursing Mothers
There are no data on the presence of mavorixafor in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise females that breastfeeding is not recommended during treatment with XOLREMDI and for 3 weeks after the final dose.
Pediatric Use
The safety and effectiveness of XOLREMDI in WHIM syndrome for increasing the number of circulating mature neutrophils and lymphocytes have been established in pediatric patients aged 12 years and older. Use of XOLREMDI for this indication is supported by evidence from an adequate and well-controlled study in adults and pediatric patients aged 12 years and older
The safety and effectiveness of XOLREMDI in WHIM syndrome for increasing the number of circulating mature neutrophils and lymphocytes have been established in pediatric patients aged 12 years and older. Use of XOLREMDI for this indication is supported by evidence from an adequate and well-controlled study in adults and pediatric patients aged 12 years and older.
Geriatic Use
In clinical studies of XOLREMDI in patients with WHIM syndrome, 2 (5%) patients were aged 65 years and older, and no patients were aged 75 years and older. Clinical studies did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients.
Gender
There is no FDA guidance on the use of Mavorixafor with respect to specific gender populations.
Race
There is no FDA guidance on the use of Mavorixafor with respect to specific racial populations.
Renal Impairment
XOLREMDI is not recommended in patients with severe renal impairment (creatinine clearance [CLcr] 15 to less than 30 mL/min) or end-stage renal disease (CLcr less than 15 mL/min). No dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to less than 90 mL/min).
No clinically significant differences in the pharmacokinetics of mavorixafor were observed in mild to moderate renal impairment (CLcr 30 to less than 90 mL/min). The pharmacokinetics of mavorixafor have not been studied in subjects with severe renal impairment or end-stage renal disease.
Hepatic Impairment
XOLREMDI is not recommended for use in patients with moderate to severe hepatic impairment. No dosage adjustment is recommended in patients with mild hepatic impairment.
The pharmacokinetics of mavorixafor have not been studied in subjects with moderate to severe hepatic impairment.
Females of Reproductive Potential and Males
XOLREMDI is expected to cause fetal harm when administered to pregnant women.
Pregnancy Testing:
Verify the pregnancy status in females of reproductive potential prior to initiating XOLREMDI.
Contraception:
Advise females of reproductive potential to use an effective form of contraception during treatment with XOLREMDI and for 3 weeks after the final dose.
Immunocompromised Patients
There is no FDA guidance one the use of Mavorixafor in patients who are immunocompromised.
Administration and Monitoring
Administration
The recommended dosage of XOLREMDI is:
Weight more than 50 kg: 400 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
Weight less than or equal to 50 kg: 300 mg orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.
Swallow the capsules whole. Do not open, break, or chew capsules.
If a dose of XOLREMDI is missed, the next dose should be taken as scheduled. Do not take more than 1 XOLREMDI dose each day.
Administer XOLREMDI on an empty stomach after an overnight fast, and at least 30 minutes before food.
Monitoring
Reduce daily dosage of XOLREMDI to 200 mg when used concomitantly with strong CYP3A4 inhibitors.
IV Compatibility
There is limited information regarding the compatibility of Mavorixafor and IV administrations.
Overdosage
There is limited information regarding Mavorixafor overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Mavorixafor Pharmacology in the drug label.
Mechanism of Action
Mavorixafor is an orally bioavailable CXCR4 antagonist that blocks the binding of the CXCR4 ligand, stromal-derived factor-1α (SDF-1α)/CXC Chemokine Ligand 12 (CXCL12). SDF-1/CXCR4 plays a role in trafficking and homing of leukocytes to and from the bone marrow compartment. Gain of function mutations in the CXCR4 receptor gene that occur in patients with WHIM syndrome lead to increased responsiveness to CXCL12 and retention of leukocytes in the bone marrow. Mavorixafor inhibits the response to CXCL12 in both wild‑type and for mutated CXCR4 variants associated with WHIM syndrome. Treatment with mavorixafor results in increased mobilization of leukocytes and lymphocytes from the bone marrow into peripheral circulation.
Structure
Mavorixafor is an orally bioavailable CXC Chemokine Receptor 4 ( CXCR4 ) antagonist.
The chemical name of the active ingredient, mavorixafor, is N1- ( 1 H-benzimidazol-2-ylmethyl ) - N1- [ ( 8 S ) -5,6,7,8-tetrahydroquinolin-8-yl ] butane-1,4-diamine. It has a molecular formula of C 21H 27N 5and a molecular weight of 349.48 g/mol. Mavorixafor is of the Sconfiguration.
Mavorixafor is of the Sconfiguration and its structural formula is provided in Figure: Structural Formulla
Pharmacodynamics
Absolute Neutrophil Count (ANC) and Absolute Lymphocyte Count (ALC):
ANC and ALC peaked at 4 hours after XOLREMDI dosing and returned towards baseline within 24 h after dosing. Over mavorixafor doses of 50 mg (0.125 times the maximum recommended dosage) to 400 mg once daily, higher mavorixafor exposure at steady state was associated with longer mean time (hours) above ANC threshold (TAT ANC) of 500 cells/µL and longer mean time (hours) above ALC threshold (TAT ALC) of 1,000 cells/µL over a 24-hour period.
Cardiac Electrophysiology:
In a thorough QT (TQT) study, the maximum mean increase in the QTc interval was 15.6 ms (upper bound of the 90% confidence interval = 19.8 ms) after administration of XOLREMDI 800 mg (2 times the maximum recommended dose) in healthy volunteers. In concentration-QT analysis, increase in QTc interval was concentration-dependent.
Pharmacokinetics
Mavorixafor pharmacokinetic parameters are presented as geometric mean (CV%) in adults with WHIM syndrome unless otherwise specified. Mavorixafor steady state C maxis 3304 (58.6%) ng/mL and the AUC from 0 to 24 hours (AUC 0-24h) is 13970 (58.4%) ng*h/mL following 400 mg once daily.
Mavorixafor demonstrates nonlinear pharmacokinetics with greater than dose-proportional increases in C maxand AUC 0-24over a dose range of 50 mg (0.125 times the recommended dosage) to 400 mg. Mavorixafor steady state is reached after approximately 9 to 12 days at the highest approved recommended dosage in healthy subjects.
Absorption:
Mavorixafor median (range) time to C max(T max) is 2.8 hours (1.9 to 4 hours) at the highest approved recommended dosage.
Effect of Food
High Fat Meal:Mavorixafor C maxdecreased by 66% and AUC decreased by 55% following single-dose administration of XOLREMDI 400 mg with a high fat meal (1000 calories, 50% fat) to healthy subjects.
Low Fat Meal:Mavorixafor C maxdecreased by 55% and AUC decreased by 51% following single-dose administration of XOLREMDI 400 mg with a low-fat meal (500 calories, 25% fat) to healthy subjects. In addition, a 14% higher mavorixafor C maxand 18% lower AUC was observed following single-dose administration of XOLREMDI 400 mg with a low-fat meal to healthy subjects after an overnight fast compared to fasting for an additional 4 hours after the XOLREMDI dose.
Distribution
Mavorixafor volume of distribution is 768 L. Mavorixafor is >93% bound to human plasma proteins in vitro.
Elimination
Mavorixafor's terminal half-life is 82 h (34%) with an apparent clearance of 62 L/h (40%) following single-dose administration of XOLREMDI 400 mg in health subjects. Mavorixafor exhibits at least partial nonlinear apparent clearance; however, this is not clinically significant at the approved recommended dosage.
Metabolism
CYP3A4 and, to a lesser extent, CYP2D6 are primarily responsible for mavorixafor metabolism.
Excretion
After a single oral dose of radiolabeled mavorixafor, 74.2% of the administered dose was recovered out of which 61.0% of administered radioactivity was recovered in feces and 13.2% (3% unchanged) was recovered in the urine over the 240-hour collection period in healthy subjects.
Specific Populations:
No clinically significant differences in the pharmacokinetics of mavorixafor were observed based on age (12 to 58 years), sex, or mild to moderate renal impairment (CLcr 30 to <90 mL/min as estimated by the Cockcroft-Gault formula). The effects of severe renal impairment (CLcr 15 to <30 mL/min), end-stage renal disease (CLcr <15 mL/min), and moderate to severe hepatic impairment on the pharmacokinetics of mavorixafor are unknown.
Lower body weight was associated with lower mavorixafor clearance. Mavorixafor exposures in patients with WHIM syndrome are comparable between those weighing 50 kg or less who receive 300 mg once daily and those weighing greater than 50 kg who receive 400 mg once daily. Following 400 mg once daily, median C maxand AUC is 22% and 30% lower, respectively, in patients with higher body weight (85 kg and above) compared to patients with average body weight (50 to less than 85 kg). The difference in exposure between patients with average body weight and patients with higher body weight is not expected to have a clinically significant impact on patient outcomes.
Pediatric Patients: No clinically significant differences in the pharmacokinetics of mavorixafor were identified in pediatric patients aged 12 to <17 years with WHIM syndrome compared to adult patients after accounting for differences in body weight.
Drug Interaction Studies:
Clinical Studies
Strong CYP3A4 Inhibitors: The systemic exposures of mavorixafor following concomitant administration of a single dose of XOLREMDI 200 mg (0.5 times the recommended dosage for adult and adolescent patients 12 years and older weighing over 50 kg) with 200 mg itraconazole (strong CYP3A4 inhibitor and P-gp inhibitor) dosed to steady state was similar to the mavorixafor systemic exposure from a single dose of XOLREMDI 400 mg administered alone in healthy subjects. These results suggest an approximate increase in mavorixafor exposure by 2-fold due to itraconazole.
CYP2D6 Substrates: Dextromethorphan (CYP2D6 substrate) C maxincreased by 6-fold (CI 90%: 5.1 to 8.3) and AUC by 9-fold (CI 90%: 6.5 to 12.3) following concomitant use with XOLREMDI 400 mg in healthy subjects.
CYP3A4 Substrates: Midazolam (CYP3A4 substrate) C maxincreased by 1.1-fold (CI 90%: 1.0 to 1.3) and AUC by 1.7-fold (CI 90%: 1.4 to 2.1) following concomitant use with XOLREMDI 400 mg in healthy subjects.
P-gp Substrates:
Digoxin C maxincreased by 1.5-fold (CI 90%: 1.3 to 1.8) and AUC increased by 1.6-fold (CI 90%: 1.4 to 1.9) following concomitant use of a single oral dose of a transporter cocktail containing 0.25 mg of digoxin with XOLREMDI dosed to steady state (400 mg/day) in healthy subjects.
Metformin:Metformin C maxdecreased by 35% (CI 90%: 17 to 49%) and AUC decreased by 35% (CI 90%: 20 to 47%) following concomitant use of a single oral dose of a transporter cocktail containing 10 mg of metformin with XOLREMDI dosed to steady state (400 mg/day) in healthy subjects.
Other Drugs: No clinically significant differences in the pharmacokinetics of caffeine (CYP1A2 substrate), losartan (CYP2C9 substrate), omeprazole (CYP2C19 substrate), furosemide (OAT1 and OAT3 substrate) and oral contraceptives were observed following concomitant use with mavorixafor.
In Vitro Studies
CYP450 Enzymes: Mavorixafor is a substrate of CYP3A4, CYP2D6, CYP3A5, and CYP2C19, but is not a substrate of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, and CYP4A11. Mavorixafor is an inhibitor of CYP3A4 (time dependent), CYP3A5, CYP2D6, CYP2B6, CYP1A2, CYP2C8, CYP2C9, and CYP2C19. Mavorixafor is an inducer of CYP1A2, but not an inducer of CYP2B6, CYP2C8, CYP2C9 and CYP3A4.
Transporter Systems: Mavorixafor is a substrate of P-gp, but not a substrate of OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 or MATE2-K. Mavorixafor is an inhibitor of P-gp, OCT2, and MATE1, but is not an inhibitor of BCRP, OATP1B1, OATP1B3, OAT1, OAT3, and MATE2-K.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Carcinogenicity studies with mavorixafor have not been conducted.
Mavorixafor was not genotoxic in an in vitrobacterial reverse mutation assay (Ames test), in an in vitrohuman lymphocyte culture chromosome aberration assay, or an in vivorat bone marrow micronucleus assay.
Fertility studies have not been conducted with mavorixafor. Significant tubular degeneration/atrophy was observed in the testes of dogs at clinical exposure.
Clinical Studies
The efficacy of XOLREMDI in patients aged 12 and older with WHIM syndrome was demonstrated in the 52-week, randomized, double-blind, placebo-controlled portion of Study 1 .Enrolled patients had a genotype-confirmed variant of CXCR4 consistent with WHIM syndrome, and a confirmed absolute neutrophil count (ANC) ≤400 cells/µL. Patients were permitted to continue (but not initiate) immunoglobulin therapy at the same dose. Use of other CXCR4 antagonists was not permitted. In Study 1, baseline demographic and disease characteristics of patients with WHIM syndrome were generally similar between the XOLREMDI and placebo groups. The mean age was 22.1 years (SD: 12.20) for the XOLREMDI group and 30.9 years (SD: 21.25) for the placebo group. Half of the patients in each group were aged 12 to <18 years, and the other half were 18 years or older. Females represented 64.3% of the XOLREMDI group and 52.9% of the placebo group, while males accounted for 35.7% and 47.1%, respectively. Most patients identified as White (93% in XOLREMDI vs. 94% in placebo), with one patient in each group identifying as either Asian or Other. In terms of ethnicity, 93% of patients receiving XOLREMDI and 100% of those on placebo were not Hispanic or Latino. Baseline immunoglobulin (Ig) use was reported in 42.9% of the XOLREMDI group and 47.1% of the placebo group. The mean baseline absolute neutrophil count (ANC) was lower in the XOLREMDI group (155 cells/µL; SD: 93.8) compared to the placebo group (281 cells/µL; SD: 232.7). Similarly, the mean baseline absolute lymphocyte count (ALC) was 501 cells/µL (SD: 204.8) in the XOLREMDI group and 563 cells/µL (SD: 199.1) in the placebo group.
Thirty-one patients were randomized 1:1 to receive either placebo (N=17) or XOLREMDI (N=14) once daily for 52 weeks. The efficacy of XOLREMDI in the treatment of patients with WHIM syndrome was based on improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections.
For ANC, the mean time (hours) above ANC threshold (TAT ANC) of 500 cells/µL over a 24-hour period was assessed 4 times throughout the study (every 3 months for 12 months). The results over the 52-week period showed that TAT ANCwas statistically significantly greater in patients treated with XOLREMDI (LS mean [SE] 15.0 [1.89] hours) compared with placebo (2.8 [1.52] hours) (p value <0.0001)
In Study 1, the mean time above the absolute neutrophil count (ANC) threshold of 500 cells/µL (TAT ANC) was evaluated for patients receiving XOLREMDI compared to those receiving placebo. At baseline, the mean (standard deviation, SD) TAT ANC was 0.0 (0.0) hours for the XOLREMDI group and 3.6 (5.7) hours for the placebo group. Based on the overall mixed-model repeated measures (MMRM) analysis, the least squares (LS) mean (standard error, SE) TAT ANC was 15.0 (1.89) hours for XOLREMDI and 2.8 (1.52) hours for placebo. The LS mean 95% confidence interval (CI) for XOLREMDI was 11.2 to 18.9 hours, and for placebo it was 0.0 to 5.9 hours. The LS mean difference between XOLREMDI and placebo was 12.3 hours (SE: 2.49), with a 95% CI of 7.2 to 17.4 hours. This difference was statistically significant with a p-value of <0.0001.
Abbreviations used include: ANC (absolute neutrophil count), CI (confidence interval), LS (least squares), MMRM (mixed-model repeated measures), SD (standard deviation), SE (standard error), and TAT (time above threshold of 500 cells/µL).
The results are based on an MMRM analysis with time above threshold as a dependent variable; treatment, visit (Weeks 13, 26, 39 and 52), treatment*visit, Ig use (randomization strata), and baseline time above threshold as covariates; and patient as the repeated random effect.
In Study 1, the Time Above Threshold (TAT) for absolute neutrophil count (ANC) over time, expressed as least squares (LS) mean ± 95% confidence interval (CI), demonstrated a consistent and notable separation between treatment groups. Patients receiving XOLREMDI showed a significantly greater TAT ANC compared to those on placebo throughout the study duration. The LS mean values for TAT ANC increased markedly over time in the XOLREMDI group, with narrow confidence intervals indicating statistical robustness, whereas the placebo group maintained relatively low and stable TAT ANC values. This figure highlights the sustained improvement in ANC levels associated with XOLREMDI treatment.
Abbreviations: ANC = absolute neutrophil count; CI = confidence interval; LS = least squares; TAT = total time (hours) above threshold (500 cells/µL) in 24 hours.
At Week 52, 3 of 17 placebo patients were given XOLREMDI in advance of their TAT measurements as they entered the open-label period of the study; one XOLREMDI patient did not take XOLREMDI. All data were included in the ITT analysis.
For ALC, the mean time (hours) above ALC threshold (TAT ALC) of 1,000 cells/µL over a 24-hour period was assessed 4 times throughout the study (every 3 months for 12 months). The results over the 52-week period showed that TAT ALCwas statistically significantly greater in patients treated with XOLREMDI (LS mean [SE] 15.8 [1.39] hours) compared with placebo (4.6 [1.15] hours) (p value <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. The Win-Ratio of 2.76 is the number of pairs of XOLREMDI-treated patient "wins" divided by the number of pairs of placebo patient "wins."
In the win-ratio analysis for the composite clinical efficacy endpoint based on total infection score and total wart change score, XOLREMDI demonstrated a win-ratio of 2.76 (95% CI: 1.60, 4.76), indicating a substantially greater clinical benefit compared to placebo. Specifically, XOLREMDI-treated patients won in 174 pair-wise comparisons on the basis of total infection score, while placebo-treated patients won in 63 such comparisons. There were no wins for either group based on total wart change score, and only one comparison resulted in a tie where no clear difference could be established. This hierarchical pair-wise comparison first evaluated total infection scores, and when those were equal, proceeded to assess total wart change scores, which were calculated by summing regional wart changes across three target lesion areas. The total infection score was determined by summing weighted infection events based on severity and adjusting for patient exposure time.
Analyses of the individual components of this composite endpoint showed an approximately 40% reduction of total infection score, weighted by infection severity, in XOLREMDI-treated patients compared with placebo-treated patients. The annualized infection rate was reduced approximately 60% in XOLREMDI-treated patients [LS mean (SE) 1.7(0.5)] compared with placebo-treated patients [LS mean (SE) 4.2(0.7)]. There was no difference in total wart change scores between the XOLREMDI and placebo treatment arms over the 52-week period.
How Supplied
XOLREMDI is supplied as an opaque white, hard gelatin capsule with a light blue cap, containing 100 mg of the active ingredient mavorixafor. The white capsule body is axially imprinted with "100 mg" in black ink, and the light blue capsule cap is axially imprinted with "MX4" in black ink.
XOLREMDI is supplied in child-resistant bottles as follows:
60 count– NDC 83296-100-60
90 count - NDC 83296-100-90
120 count– NDC 83296-100-12
Storage
XOLREMDI refrigerated at 2°C to 8°C (36°F to 46°F). Keep bottle tightly closed. Store in and dispense from original container to protect from moisture.
Images
Drug Images
{{#ask: Page Name::Mavorixafor
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
Package and Label Display Panel
NDC 83296-100-60
XOLREMDI™
(mavorixafor) capsules
100 mg
Swallow the capsules whole.
Do not open, break, or chew capsules.
Rx only
60 capsules
This image is provided by the National Library of Medicine
Advise patients to take XOLREMDI on an empty stomach after an overnight fast, 30 minutes before food. Advise patients to swallow the capsules whole and not to open, break, or chew capsules.
Embryo-Fetal Toxicity
XOLREMDI is expected to cause fetal harm. Advise females of reproductive potential to use an effective form of contraception during treatment with XOLREMDI and for 3 weeks after the final dose. Advise females to inform their healthcare provider of a known or suspected pregnancy.
Lactation
Advise females that breastfeeding is not recommended during treatment with XOLREMDI and for 3 weeks after the final dose.
Drug Interactions
Advise patients to avoid taking dietary supplements that include goldenseal, as it is a strong CYP3A4 inhibitor and may increase risk of adverse reactions to XOLREMDI.
Advise patients to avoid taking dietary supplements that include St. John's Wort, as it is an inducer of CYP3A4 and may reduce the efficacy of XOLREMDI.
Food Interactions
Advise patients to avoid eating or drinking products with grapefruit, as grapefruit is a strong CYP3A4 inhibitor and may increase the risk of adverse reactions to XOLREMDI.
Precautions with Alcohol
Alcohol-Mavorixafor interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
XOLREMDI
Look-Alike Drug Names
There is limited information regarding Mavorixafor Look-Alike Drug Names in the drug label.
