WHIM syndrome is a rare genetic disease that affects your immune system and can cause frequent, potentially serious infections.
Xolremdi (mavorixafor) was approved in 2024 and is the first medicine approved to treat the underlying cause of WHIM syndrome and improve the function of the immune system.
What Is WHIM Syndrome?
WHIM syndrome is a rare disease that affects your immune system, which is how your body prevents and treats infections. The letters in WHIM stand for symptoms that happen when you have the disease: warts, hypogammaglobulinemia, infections, and myelokathexis. These symptoms are further discussed below.
- Warts: People with WHIM syndrome can get infections from a virus called human papillomavirus (HPV), which can cause warts on the skin or genitals and increase your risk for certain types of cancer.
- Hypogammaglobulinemia: Some people with WHIM syndrome have low levels of infection-fighting antibodies (a medical term called hypogammaglobulinemia), because they have low levels of B cells (a type of white blood cell). This increases the risk of developing an infection.
- Infections: Because of its effects on the immune system, people with WHIM syndrome can get frequent infections. These infections commonly occur in the lungs, ears, or skin.
- Myelokathexis: White blood cells, which are the cells in your body that help fight infections, are made in the bone marrow. Myelokathexis occurs when your white blood cells are stuck in your bone marrow and cannot get out to travel to the site of infection to help treat it.
Not every person with WHIM syndrome will have all four of these symptoms. Some people may only have mild symptoms that do not greatly impact their day-to-day life, while others can develop frequent and potentially life-threatening infections.
How Does Xolremdi Work for WHIM Syndrome?
As mentioned above, people with WHIM syndrome have myelokathexis (a condition that causes white blood cells to be trapped in the bone marrow). Myelokathexis happens when there is a mutation in a certain gene called the CXC chemokine receptor 4 (CXCR4) gene. The CXCR4 gene codes for a certain type of protein in the body called the CXCR4 receptor. Chemokine receptors like CXCR4 tell white blood cells where to travel in the body to fight infections. When there is a mutation in the CXCR4 gene, the CXCR4 receptor does not work right, and white blood cells can build up and become trapped in the bone marrow. Xolremdi works by blocking the CXCR4 receptor, which lets the white blood cells leave the bone marrow so that they can help fight infections.
How Do I Use Xolremdi?
Xolremdi is a capsule that is taken by mouth once per day on an empty stomach. You should take your dose of Xolremdi first thing in the morning, after having not eaten anything overnight. Wait at least 30 minutes after taking Xolremdi to eat anything. The specific dose that you will take will depend on how much you weigh.
How Was Xolremdi Studied for WHIM Syndrome?
A clinical study was done to see if Xolremdi was safe and effective for the treatment of WHIM syndrome. The study included 31 people with WHIM syndrome, which was confirmed by testing for a mutation in their CXCR4 gene. People in the study also had to have a low level of neutrophils (a type of white blood cell). Anyone who was already using immunoglobulins before the study could continue to use them during the study.
People in the study were, on average, between 17 and 23 years old. About half of the people in the study were between 12 and 17 years old, and just over half were female. Most people were White (about 94%), one person was Asian, and the rest of the people in the study reported a race of “other.” Less than a quarter of people in the study lived in the United States.
People in the study either took oral Xolremdi once daily or a daily placebo pill that did not contain any medicine. The study researchers measured the effectiveness of Xolremdi by evaluating the absolute neutrophil count (a blood test that counts the number of a certain type of white blood cells called neutrophils) over 24 hours. The main outcome that the study researchers looked at was the number of hours in a day that each person in the study had an absolute neutrophil count that was at least 500 cells per microliter; this measurement was performed once every three months over a year. People with an absolute neutrophil count of at least 500 cells per microliter are less likely to get an infection than people with an absolute neutrophil count below 500 cells per microliter. The researchers also looked at the effects of treatment on another type of white blood cell (lymphocytes) and calculated the annual infection risk in each group.
What Benefits of Xolremdi Were Seen?
People treated with Xolremdi spent about 12 more hours per day with absolute neutrophil counts of at least 500 cells per microliter than people who took the placebo. Xolremdi had similar effects on lymphocyte counts. People who took Xolremdi kept their lymphocyte counts above a target level of 1,000 cells per microliter (the cutoff for an increased risk of infection) for about 11 more hours per day compared to people who took placebo.
Based on calculations performed, people treated with Xolremdi had less than two infections per year, while people treated with placebo had more than four infections per year.
Your results may differ from what was seen in clinical studies.
Who Should Not Use Xolremdi?
Xolremdi should not be used if you have more severe kidney or liver problems, or if you are pregnant or breastfeeding. Your health care provider will help you decide if Xolremdi is right for you.
Xolremdi can affect the levels of certain medicines in your blood and should not be taken at the same time due to risk of side effects (see Interactions section). Tell your health care provider about all the medicines you are taking before you start Xolremdi.
What Types of Drug Interactions Can Happen?
Several medicines can interact with Xolremdi. These interactions can decrease how well Xolremdi works or increase your risk of side effects. Some medicines that inhibit proteins called P-glycoprotein (P-gp) or CYP3A4 can increase your risk of side effects if they are taken together. Your health care provider may need to lower your dose of Xolremdi if it is taken with a P-gp or CYP3A4 inhibitor.
Other medicines are called strong inducers of CYP3A4. These medicines may make Xolremdi work not very well. Ideally, Xolremdi should not be taken together with strong CYP3A4 inducers.
Xolremdi can increase your risk of side effects from certain other medicines too. These medicines are called substrates of CYP2D6, CYP3A4, or P-gp.
Xolremdi also interacts with medicines that can cause QT prolongation, which is a potentially dangerous heart rhythm problem.
This is not a complete list of interactions. Tell your pharmacist or health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions with Xolremdi or if you need the dosage adjusted.
How Can I Manage Side Effects?
The most common side effects of Xolremdi are low platelet count (thrombocytopenia), rash (including a specific kind of rash called pityriasis that causes dry, scaly patches), nose bleeding or irritation, vomiting, and dizziness.
Low platelet levels can cause bleeding. Tell your health care provider if you bruise or bleed easily while taking Xolremdi. If you get a nosebleed, sit upright and hold the soft sides of your nose closed using your thumb and index finger. You can use a tissue to catch the blood. Continue to hold the nose closed with steady pressure for at least a few minutes until the bleeding stops. Get help right away if you are bleeding a lot or the bleeding does not get better after about 20 minutes.
If you experience vomiting, make sure to drink lots of fluids. Eating smaller or lighter meals may also help to reduce vomiting.
Dizziness can cause falls. If you get dizzy while taking Xolremdi, avoid any sudden head movements or getting up too quickly from a sitting or lying position.
These are not all the possible side effects of Xolremdi. Contact your health care provider for medical advice about side effects if you are having symptoms that bother you. You can also report side effects to the FDA at 800-FDA-1088 (800-332-1088).
Getting Your Medicine: What to Expect
Xolremdi is considered a specialty medicine, which is a high-cost medicine that is taken for rare, complex, or chronic diseases. It requires a different process than picking up a prescription at your local pharmacy. This process helps you stay on track with your treatment. The drugmaker has a program to help support the process.
Here are some differences that you may expect.
Insurance approval. Your insurance may require approval for using this medicine, also called a prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered.
Pharmacy access. You will use a specific pharmacy to get your medicine. Your health care provider will work with you and the drugmaker on which pharmacy to use and the information that will be provided. The pharmacy will work with your insurance company to determine the costs. They will also talk with you each month to review your treatment and schedule your delivery.
Copay assistance. There is a copay assistance program from the drugmaker that may allow you to pay $0 for your prescription. For questions or more information, you can contact the drugmaker at 844-942-6628 or visit www.xolremdi.com/resources/x4connect.