Drug Trials Snapshots: XOLREMDI
XOLREMDI (mavorixafor)
zol-REM-dee
X4 Pharmaceuticals, Inc.
Original Approval date: April 26, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
XOLREMDI is a prescription drug that increases the number of white blood cells released from the bone marrow into the blood. XOLREMDI is indicated for the treatment of adults and adolescents over the age of 12 years with WHIM (Warts, Hypogammaglobulinemia, Infection, and Myelokathexis) syndrome.
How is this drug used?
XOLREMDI is a capsule taken by mouth once a day.
Who participated in the clinical trials?
The FDA approved XOLREMDI based on evidence from a clinical trial (NCT03995108) of 31 patients with WHIM syndrome. The trial was conducted at 19 sites in 12 countries in North America, Europe, Australia, and Asia. Of the 31 patients, 6 patients were from trial sites in the United States.
The benefits and side effects of XOLREMDI were evaluated in the same single clinical trial.
How were the trials designed?
XOLREMDI was evaluated in one clinical trial of 31 patients with WHIM syndrome.
The trial was a randomized, double-blind, placebo-controlled trial in patients aged 12 years and older with WHIM syndrome. The patients were randomized to receive either placebo or XOLREMDI 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.
How were the trials designed?
The safety and efficacy of XOLREMDI in patients aged 12 years and older with WHIM syndrome was demonstrated in the 52-week, randomized, double-blind, placebo-controlled portion of a single clinical trial. Enrolled patients had a genotype-confirmed variant of CXCR4 consistent with WHIM syndrome, and a confirmed ANC ≤400 cells/μL. Thirty-one patients were randomized to receive either placebo (N=17) or XOLREMDI (N=14) once daily for 52 weeks.
The efficacy of XOLREMDI was based on improvement in ANC, improvement in ALC, and a reduction in infections in patients randomized to XOLREMDI compared to patients randomized to placebo.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the trial used to evaluate the efficacy of XOLREMDI.
Figure 1. Baseline Demographics by Sex
Figure 2 summarizes how many patients by race were enrolled in the trial used to evaluate the efficacy of XOLREMDI.
Figure 2. Baseline Demographics by Race
Figure 3 summarizes how many patients by age were enrolled in the trial used to evaluate the efficacy of XOLREMDI.
Figure 3. Baseline Demographics by Age
Figure 4 summarizes how many patients by ethnicity were enrolled in the trial used to evaluate the efficacy of XOLREMDI.
Figure 4. Baseline Demographics by Ethnicity
Who participated in the trials?
Table 1. Baseline Demographics
| Characteristic | XOLREMDI N=14 |
Placebo N=17 |
| Sex, n (%) | ||
| Female | 9 (64.3) | 9 (52.9) |
| Male | 5 (35.7) | 8 (47.1) |
| Age, years | ||
| Mean (SD) | 22.1 (12.2) | 30.9 (21.3) |
| Median (min, max) | 17.5 (12, 58) | 23 (13, 72) |
| Age group, years, n (%) | ||
| <18 | 7 (50.0) | 8 (47.1) |
| ≥18 to <65 | 7 (50.0) | 7 (41.2) |
| ≥65 | 0 | 2 (11.8) |
| Race, n (%) | ||
| Asian | 0 | 1 (5.9) |
| Other | 1 (7.1) | 0 |
| White | 13 (92.9) | 16 (94.1) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 1 (7.1) | 0 |
| Not Hispanic or Latino | 13 (92.9) | 17 (100) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
Compared to patients who had received placebo, patients who received XOLREMDI had higher numbers of white blood cells and fewer infections.
The efficacy of XOLREMDI in the treatment of patients with WHIM syndrome was based on improvement in ANC, improvement in ALC, and a reduction in infections in the 52-week, randomized, double-blind, placebo-controlled study where 14 patients received XOLREMDI and 17 patients received placebo.
For ANC, the mean time above the ANC threshold of 500 cells/μL over a 24-hour period assessed four times throughout the study was significantly greater in patients treated with XOLREMDI (15.0 hours) compared with placebo (2.8 hours). For ALC, the mean time above the ALC threshold of 1,000 cells/μL over a 24-hour period assessed four times throughout the study was significantly greater in patients treated with XOLREMDI (15.8 hours) compared with placebo (4.6 hours).
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 (Table 2).
Table 2. Win-Ratio Analysisa for the Composite Clinical Efficacy Endpoint Based on Total Infection Score and Total Wart Change Score
| Category | nb | Win-Ratio (95% CI) |
| XOLREMDI wins on total infection score | 174 | 2.76 (1.60, 4.76) |
| Placebo wins on total infection score | 63 | |
| XOLREMDI wins on total wart change score | 0 | |
| Placebo wins on total wart change score | 0 | |
| None of the above (tie) | 1 |
Source: Adapted from FDA Review
aThe method compared each XOLREMDI-treated patient to each placebo-treated patient in a pair-wise manner that proceeded in a hierarchical fashion using total infection score, followed by total wart change score if patients could not be differentiated based on total infection score. The total infection score was calculated by summing up the number of infection events weighted by severity and divided by the total exposure time (in years). Total wart change score was calculated by summing up the regional wart change scores from three target regions (lesions).
b n is number of wins
Abbreviations: CI, confidence interval
The efficacy of XOLREMDI was further assessed in an analysis of the individual components of the composite endpoint. XOLREMDI-treated patients had an approximately 40% reduction of total infection score and an approximately 60% reduction in annualized infection rate compared with placebo-treated patients. There was no difference in total wart change scores between the XOLREMDI and placebo treatment arms over the 52-week period.
What are the possible side effects?
The most common side effects were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.
XOLREMDI may cause clinically significant QTc interval prolongation.
XOLREMDI is expected to cause fetal harm. Females of reproductive potential should use effective contraception and XOLREMDI should not be prescribed during pregnancy.
What are the possible side effects (results of trials used to assess safety)?
Table 3. Adverse Reactions in ≥10% Patients With WHIM Syndrome Receiving XOLREMDI and More Frequently Reported Than Placebo
| Adverse Reaction |
XOLREMDI N=14 n (%) |
Placebo N=17 n (%) |
| Thrombocytopenia | 3 (21) | 0 |
| Pityriasis | 2 (14) | 0 |
| Rash | 2 (14) | 0 |
| Rhinitis | 2 (14) | 0 |
| Epistaxis | 2 (14) | 1 (6) |
| Vomiting | 2 (14) | 1 (6) |
| Dizziness | 2 (14) | 1 (6) |
Source: Adapted from FDA Review
Abbreviations: WHIM, Warts, Hypogammaglobulinemia, Infection, and Myelokathexis
Serious adverse reactions of thrombocytopenia occurred in 3 of the 14 patients who received XOLREMDI, two of which occurred in the setting of infection and febrile neutropenia.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The effect of XOLREMDI was similar for females and males.
- Race: The number of patients of races other than White was small; therefore, differences in how XOLREMDI worked among races could not be determined.
- Age: The number of patients older than 65 years of age was small; therefore, differences in how XOLREMDI worked between patients younger and older than 65 years of age could not be determined. The effect of XOLREMDI was similar for patients younger and older than 18 years of age.
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The majority of patients in the trial were White. Differences in the occurrence of side effects could not be determined because of the small number of patients in other races.
- Age: The majority of patients in the trial were younger than 65 years old. Differences in the occurrence of side effects in patients 65 years of age or older could not be determined because of the small number of patients.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
