Fayuvi (rebisufligene etisparvovec-hopf) is a one-time gene therapy given as a single IV infusion (into a vein) for children with Sanfilippo syndrome type A, also called mucopolysaccharidosis type IIIA (MPS III-A).
Like all medicines, Fayuvi can cause side effects. The oral corticosteroid medicine your child takes alongside Fayuvi may also affect when certain vaccines can be given.
Keep reading to learn about possible Fayuvi side effects, how to help manage them, and what to know about vaccines during treatment.
This article doesn't include every possible side effect. Tell your child's health care provider about any symptoms that concern you or don't improve.
Fayuvi Side Effects
Common side effects
In clinical studies, the most commonly reported side effects in children who received the recommended dose of Fayuvi included:
- Liver enzyme increases (a sign of temporary liver stress, found on blood tests)
- Vomiting
- Behavioral changes, such as irritability, agitation, or trouble sleeping
- Diarrhea
- Fever
- Low white blood cell counts
- Cushingoid features (rounder face, weight changes, and other appearance changes linked to corticosteroid use)
- Decreased appetite
- Low platelet counts
- Low red blood cell counts (anemia)
Serious side effects
Fayuvi also carries the possibility of more serious side effects, including liver problems, thrombotic microangiopathy (a serious blood vessel problem, explained below), infusion or allergic reactions, and a small possible risk of cancer (malignancy) related to how gene therapies work.
If you notice symptoms that feel serious or life-threatening, seek medical care right away.
How to Manage Fayuvi Side Effects
While not a complete guide, the following information can help you know what to expect and how to help manage some of the more common or important side effects of Fayuvi.
1. Liver enzyme increases
Liver enzyme increases are the most commonly reported side effect of Fayuvi, affecting the large majority of children who receive the recommended dose in clinical studies. Most of these increases were mild to moderate.
So, your child will take an oral corticosteroid medicine starting the day before the infusion and continue it for a minimum of eight weeks. The dose will then be gradually reduced (tapered down) to help lower the chance of liver-related side effects. Your child's health care provider will check liver blood tests regularly before and after the infusion; they may increase or extend the corticosteroid dose if your child's liver enzymes are rising or stay elevated.
Watch for yellowing of the skin or the whites of the eyes (jaundice), which can be a sign of a liver problem; if you notice this or if your child misses a dose of the corticosteroid or vomits it up,
contact your child's health care provider right away.
Don't give your child any new medicines, herbal products, or supplements, including over-the-counter (OTC) products, without first checking with a health care provider or pharmacist.
2. Low platelet counts (thrombocytopenia)
Platelets are blood cells that help with clotting. A drop in platelet counts can increase the risk of unusual bruising or bleeding. It has been reported to occur within the first two weeks after the Fayuvi infusion.
Your child's health care provider will check platelet counts weekly for the first four weeks after treatment, then monthly for six months. Keeping these appointments is important for catching a drop in platelets early.
Contact your child's health care provider if you notice unexpected bruising, small red or purple spots on the skin, bleeding gums, or nosebleeds that are hard to stop.
3. Thrombotic microangiopathy (a serious blood vessel problem)
Thrombotic microangiopathy (TMA) is a rare but serious complication that has been reported with gene therapies that use an adeno-associated virus (AAV) vector, the same type of vector used in Fayuvi. TMA involves small blood clots that can damage blood vessels, red blood cells, and the kidneys.
Watch for a combination of unexpected bruising or bleeding, swelling, seizures, high blood pressure, or a noticeable drop in the amount of your child's pee.
Seek medical attention right away if you notice these symptoms, especially if they happen together. Your child's health care provider can order blood and urine tests to check for hemolytic anemia (a type of red blood cell breakdown) and kidney problems that can occur with TMA.
4. Vomiting, diarrhea, and appetite changes
Digestive symptoms, including vomiting, diarrhea, and a decreased appetite, were commonly reported after Fayuvi infusion.
To help manage these at home:
- Offer small, frequent sips of fluid to help prevent dehydration, especially after vomiting or diarrhea.
- Offer bland, easy-to-digest foods (such as rice, bananas, or toast) as appetite returns.
- Avoid greasy or high-fiber foods that may worsen diarrhea.
- Keep a log of how often symptoms occur, as your child's health care provider may ask about this at follow-up visits.
Contact your child's health care provider if vomiting or diarrhea is severe, doesn't improve, or if you notice signs of dehydration, such as a dry mouth, fewer wet diapers, or unusual sleepiness. Remember, your child may miss a dose of their corticosteroid if it's vomited out, so inform your child's health care provider right away if this happens.
5. Fever and infusion reactions
Fever was commonly reported after Fayuvi infusion. Separately, infusion reactions (including hypersensitivity reactions and, rarely, anaphylaxis, a severe allergic reaction) can happen during or shortly after the infusion itself. Symptoms of an infusion reaction may include low blood pressure, fever, a fast or pounding heartbeat, nausea, vomiting, chills, or headache.
So, Fayuvi is given in a setting with staff and equipment ready to treat infusion and allergic reactions. Also, your child is monitored closely during and after the infusion. If a reaction happens, the infusion may be paused and restarted more slowly once symptoms resolve.
After you go home, contact your child's health care provider about a fever, and ask in advance what fever level or other symptoms should prompt a call.
6. Side effects from the corticosteroid medicine
Because your child will take a corticosteroid for at least eight weeks around the time of the Fayuvi infusion, some reported side effects come from the corticosteroid itself rather than from Fayuvi. These can include behavioral changes (such as irritability, agitation, anxiety, or trouble sleeping), Cushingoid features (a rounder face, weight gain, or other appearance changes), and, less often, adrenal insufficiency (when the body's own natural steroid production is temporarily suppressed).
Tell your child's health care provider about any new or worsening behavior changes, since these can sometimes be managed by adjusting the corticosteroid regimen. Don't stop or change the corticosteroid dose on your own, even if your child seems to be doing well, since stopping too quickly can affect how the body responds and may need to be done gradually under medical supervision.
Fayuvi and Vaccines
Fayuvi itself hasn't been studied for interactions with other medicines in the way oral medicines typically are, since it's given once as an infusion. However, the corticosteroid your child takes before and after the Fayuvi infusion can affect how well vaccines work and how safely they can be given.
Corticosteroids can temporarily slow your immune response, including its response to vaccines. Vaccines are generally recommended to be avoided for 30 days before starting Fayuvi (and the corticosteroid) and avoided while your child is on corticosteroid therapy.
Before scheduling the Fayuvi infusion, talk to your child's pediatrician and the gene therapy treatment team about your child's vaccination schedule. They can help you plan which vaccines to give ahead of time and when it will be safe to resume your child's regular vaccine schedule once the corticosteroid taper is complete. Don't adjust your child's vaccine schedule on your own; work with both your child's pediatrician and the treatment center to coordinate timing.
Reducing Your Child's Risk of Side Effects
You can help lower the risk of side effects by making sure your child attends every recommended follow-up visit and lab test and by following the treatment team's instructions closely.
Helpful tips include:
- Tell every health care provider and pharmacist involved in your child's care about all prescription medicines, OTC products, and any vitamins, herbs, or other supplements your child uses.
- Ask before starting, stopping, or changing any medicine, including the corticosteroid.
- Report new or worsening symptoms to your child's health care provider, rather than waiting to see if they resolve on their own.
Your child's health care provider can adjust the corticosteroid regimen or monitoring plan as needed to help manage side effects. Don't change or stop any part of your child's treatment plan without talking with the health care provider first.