Wiskott-Aldrich syndrome (WAS) is a rare, inherited condition that causes people to be more prone to infections and bleeding. A gene therapy known as Waskrya (etuvetidigene autotemcel) is available for children and adults with WAS who are eligible for hematopoietic stem cell transplantation but don’t have a matched stem cell donor.
How Does Waskyra Work for Wiskott-Aldrich Syndrome?
People with WAS have a gene mutation in the WAS gene. This mutation makes them unable to produce the normal WAS protein, which is needed for the immune system and platelets to work properly. Waskrya is a gene therapy in which stem cells are collected and then sent to a lab, where a functional copy of the WAS gene is added. The stem cells are then infused back into the body. Once in the body, the functional gene helps the body make healthy blood cells, which corrects the underlying condition.
How Will I Receive Waskyra?
Waskyra is given as a one-time IV infusion (infusion into a vein) in the hospital. The treatment uses your own blood stem cells that have been changed in a lab to fix the faulty gene. Before getting the treatment, you will need to go through a process called stem cell mobilization to collect your stem cells from your blood. Then, you will receive a medicine called rituximab followed by chemotherapy to prepare your body for the re-infusion of the stem cells, which is called conditioning.
Once your conditioning regimen is complete, the genetically corrected stem cells are infused into your body in a process similar to a regular blood transfusion. You will continue to receive other medicines and will be monitored closely in the hospital until engraftment occurs. Engraftment is when the stem cells start producing new, healthy blood cells. Once blood cell counts are stable and engraftment has occurred, you will be discharged from the hospital.
Because the immune system needs to fully recover, you may still be at high risk of infection after engraftment and discharge from the hospital. So, interactions with visitors and leaving your home will be restricted for a while. You will also continue to have lab appointments and follow-up visits to the hospital after discharge.
How Was Waskyra Studied?
Two clinical studies and one expanded access program looked at the efficacy of Waskyra for treating WAS. Participants knew what treatment they were getting and had a diagnosis of WAS confirmed by genetic mutation. To join the study, people also needed to have at least one of the following:
- Zhu score of ≥ 3 out of 5 (indicating severe disease)
- Severe WAS mutation
- Absent WAS protein expression.
All people who received Waskyra did not have a suitable stem cell donor.
People were not allowed in the studies or expanded access program if they had any of the following:
- Prior allogeneic hematopoietic stem cell transplant within six months or evidence of residual cells
- Prior gene therapy
- HIV infection
- Genetic alterations indicating other potential conditions
In total, there were 27 people who received Waskyra. The median (middle) patient age was 2.6 years of age (range, 1-35 years). All people who received Waskyra were male. Most (74%) were White, 15% were Asian, 7% were African American, and 1 person was American Indian or Alaska Native; 11% identified as Hispanic or Latino ethnicity. Each person received rituximab and a chemotherapy conditioning regimen that consisted of busulfan and fludarabine.
What Benefits Were Seen With Waskyra?
Severe infections and moderate to severe bleeding episodes occurred less often in people after receiving Waskyra.
Compared to a rate of two severe infections per year before receiving Waskyra, infections dropped to 0.2 per year in the 6-to 18-month period after receiving Waskyra.
The rate of moderate to severe bleeding episodes also declined from two events per year in the 12 months before receiving Waskyra to 0.8 events per year in the 12 months after receiving Waskyra.
Your results may differ from what was seen in clinical studies.
How Long Does It Take Waskyra to Work?
Engraftment is when the gene-corrected stem cells settle in the bone marrow and begin making healthy blood cells. This can vary but usually takes about 26 days on average. You will need to take precautions during this period to protect yourself from infection, and you will continue to have lab and hospital visits as your immune system recovers. If everything goes well, people typically regain a normal immune system within one year of receiving Waskyra gene therapy and can live a normal life.
What Are Common Waskyra Side Effects and How Can I Prevent or Manage Them?
The most common side effects with Waskyra observed in clinical studies were catheter related infections, bacterial and viral infections, diarrhea (frequent, loose, watery stools), vomiting, canker sores, liver injury, head injury, runny nose, cough, rash, petechiae (tiny spots under the skin indicating bleeding), hypersensitivity (allergic) reactions, low red blood cell levels (anemia), low white blood cell count with a fever, nose bleeds, fever alone, and catheter site complications.
Waskyra increases your risk of infection because of how it affects your immune system. The most common infections in clinical studies were catheter-related infections, respiratory tract infections, cytomegalovirus infections, and urinary tract infections. It is important to use good hygiene practices such as disinfecting surfaces, washing your hands, and avoiding touching your face. You should also avoid being in close contact with people who are sick and should avoid large crowds.
When you get a central venous catheter, a health care provider will show you how to take care of it. You should follow the instructions from your health care provider on how to take care of your catheter. They may give you instructions on how to change the dressing or catheter parts to prevent infection. It is important to keep your catheter clean and dry. You should call your health care provider right away if you develop any signs of infection, such as:
- Fever or chills
- A cough that does not go away
- Painful urination
- Feeling dizzy or lightheaded
- Redness, swelling, or fluid around the catheter site
- Chest tightness or shortness of breath
If diarrhea is present for more than 24 hours in children or three days in adults during treatment with Waskyra, contact your health care provider. You may be at risk for dehydration, and your health care provider can recommend ways to treat it.
If a rash occurs or there are other signs of an allergic reaction, your health care provider will treat you with antihistamines and possibly other medications. If you notice that you are having a severe reaction, or your symptoms are coming back or getting worse, you should seek emergency care.
If you develop canker sores after receiving Waskyra, rinsing your mouth with salt water can help with inflammation and healing. Also, avoiding spicy or acidic foods can help minimize irritation.
Waskyra may cause low levels of one or more types of blood cells, which can make you feel weak or tired or increase your risk of infection. Tell your health care provider if you have any signs of infection or generally feel weak or unwell. Keep all appointments to have your blood checked.
Bleeding episodes are more common in people with WAS but should occur less often after receiving Waskyra. If you notice petechiae (tiny spots under the skin indicating bleeding), let your health care provider know. Nosebleeds are more likely to occur in low-humidity environments; using a humidifier may help prevent them. If a nosebleed occurs, sitting up and not lying down can help it stop, and also pinching your nostrils closed for 5-10 minutes. If your nosebleed persists or you get frequent nosebleeds, talk to your health care provider.
These are not all the possible side effects of Waskyra. Contact your health care provider for medical advice about side effects. You can report side effects to the FDA at 800-FDA-1088 (800-332-1088) or www.fda.gov/medwatch. You can also report side effects to the drugmaker at 888-212-6928.Waskyra.
What Are Other Unique Considerations to Be Aware Of?
People who receive Waskyra should not donate blood, organs, or tissues at any time in the future.
People should avoid receiving antiretroviral medicines for at least one month prior to stem cell collection and for at least seven days after receiving the Waskyra infusion. Check with your health care provider before starting any antiretroviral (HIV) medicines.
People should avoid receiving certain types of vaccines called live vaccines until their immune system has recovered after Waskyra infusion. Check with your health care provider before getting any vaccines.
Before you receive Waskyra, your health care provider will make sure you are not pregnant. If you would like to get pregnant after getting Waskyra, talk with your health care provider. People who can get pregnant or get a partner pregnant should use an effective method of birth control from the start of stem cell mobilization through at least six months after receiving Waskyra.
Waskyra can increase your risk of developing secondary cancers. Your health care provider will monitor you annually for the development of other cancers for at least 15 years after receiving