Fayuvi

Fayuvi is a prescription gene therapy for children with Sanfilippo syndrome type A. It is designed to help stop or slow lasting damage to the brain and nervous system, and the loss of skills that comes with it. It can be used in patients who still have most of their thinking, language, and motor skills.

Fayuvi works by delivering a working copy of the SGSH gene, which lets cells make sulfamidase. This enzyme breaks down heparan sulfate, the substance that builds up in cells and damages nerve cells in the brain in people with MPS IIIA.

Fayuvi is given as a one-time infusion into a vein that takes about 1 hour.

Fayuvi's active ingredient is rebisufligene etisparvovec-hopf, which was also known as UX111 and ABO-102 during clinical development.

Sanfilippo syndrome type A is also called mucopolysaccharidosis type IIIA or MPS IIIA.

Fayyvi is FDA-approved to be used for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A) in pediatric patients with preserved neurodevelopmental function. It was first approved by the FDA on September 17, 2026.

Sanfilippo syndrome type A, also called mucopolysaccharidosis type IIIA or MPS IIIA, is a rare inherited disease that damages the brain and nervous system.

Children with MPS IIIA inherit a changed SGSH gene from both parents. This gene normally tells the body how to make an enzyme called sulfamidase, which breaks down a complex sugar called heparan sulfate. Without working sulfamidase, heparan sulfate builds up inside cells and damages nerve cells in the brain.

Symptoms start in early childhood as delayed development. Children then lose skills they had already learned, with declines in thinking, speech, and movement, along with behavior problems.

Fayuvi is a gene therapy that provides a working copy of the SGSH gene, which does not work properly in people with MPS IIIA.

It uses a modified virus (adeno-associated virus serotype 9, or AAV9) to carry the working gene into cells around the body. Those cells can then make sulfamidase, the enzyme that is missing or not working properly in MPS IIIA.

Sulfamidase works inside lysosomes, the parts of the cell that break down waste. Once cells can make sulfamidase, they can start breaking down the heparan sulfate that damages nerve cells in the brain.

Fayuvi is an adeno-associated virus (AAV) vector-based gene therapy.

Fayuvi is given one time only, as a slow drip into a vein (intravenous infusion) that takes about 1 hour.

The dose is based on your child's weight. Children weighing more than 70 kg (about 154 pounds) receive the 70 kg dose.

The infusion is given in a hospital or clinic where staff can treat a reaction straight away. If your child has a reaction during the infusion, the team will pause it and may restart it more slowly once your child is feeling better.

There is no second dose. Fayuvi is designed to be a one-time treatment.

Fayuvi can cause liver problems, low platelet counts, and serious allergic reactions. Your child will need blood tests before treatment and for several months afterward.

Your child will take a steroid medicine (a corticosteroid, such as prednisone or prednisolone) by mouth starting the day before the infusion. This is given to protect the liver. It continues for at least 8 weeks and is then lowered slowly over at least 4 more weeks. Do not stop this medicine early. Call your child's doctor if your child misses a dose or vomits it up.

Call your child's doctor right away if your child has yellowing of the skin or the whites of the eyes, which can be a sign of a liver problem.

Get medical help right away if your child has unexpected bruising or bleeding, seizures, or is passing much less urine than usual. These can be signs of a serious blood and kidney problem called thrombotic microangiopathy (TMA).

Cancer is a possible risk after treatment with gene therapies like Fayuvi. If your child is diagnosed with cancer after treatment, contact your child's doctor and Ultragenyx Pharmaceutical at 1-888-756-8657.

Before your child receives Fayuvi, the care team will run several tests and checks.

• Blood tests. Liver function tests and tests of platelet count and blood clotting are done before the infusion.
• Antibody testing. Your child will be tested for antibodies to AAV9, the virus used to deliver the gene. Fayuvi is not recommended for children who already have high levels of these antibodies, because the treatment may not work. There is no FDA-authorized test for this yet, so the care team may need to contact the manufacturer for testing information.
• Infections. Treatment is delayed until any significant infection is under control, because the steroid medicine affects the immune system.
• Vaccines. Your child should not receive vaccines in the 30 days before treatment or at any time while taking the steroid medicine. Talk to your child's doctor about adjusting the vaccination schedule.

Fayuvi has not been studied in adults aged 65 and older.

Females who can become pregnant must have a negative pregnancy test before treatment. People who are pregnant or planning to become pregnant should not receive Fayuvi. There is no information on whether Fayuvi passes into breast milk or affects fertility.

The most common Fayuvi side effects are increased liver enzymes, vomiting, behavior changes, diarrhea and fever. Increased liver enzymes affected 85% of children in clinical studies and were usually mild to moderate.

Common Fayuvi side effects

These side effects were reported in 27 children who received the approved dose of Fayuvi in clinical studies (Study 1, 2, and 3):

• Increased liver enzymes (85%), measured by blood test
• Vomiting (67%)
• Behavior changes including irritability, agitation, aggression, anxiety and trouble sleeping (56%)
• Diarrhea (48%)
• Fever (41%)
• Low white blood cell count (30%)
• Cushingoid features such as a rounded face and weight gain around the middle (30%)
• Reduced appetite (22%)
• Low platelet count (19%)
• Anemia, or low red blood cell count (19%)
• Constipation (15%)
• Nausea (11%)
• Increased amylase, a pancreatic enzyme (11%)
• Increased alkaline phosphatase, a liver and bone enzyme (11%)
• Seizures (11%)
• Enlarged liver (11%)
• Muscle stiffness (7%)
• Low potassium (7%)
• Trouble walking (7%)
• Adrenal gland problems (7%)

Almost all liver enzyme increases returned to normal. In 2 children, slightly raised levels continued.

What are the serious side effects of Fayuvi?

Get medical help right away if your child has any of these signs after a Fayuvi infusion:

• Liver problems. Yellowing of the skin or the whites of the eyes.
• Low platelets. Unexpected bruising or bleeding.
• Thrombotic microangiopathy (TMA). Unexpected bruising or bleeding, seizures, or passing much less urine than usual. TMA is a serious condition affecting small blood vessels, the blood, and the kidneys. It has been reported with other AAV gene therapies, though no cases occurred in Fayuvi studies.
• Allergic and infusion reactions. Low blood pressure, fever, a racing heart, nausea, vomiting, chills, or headache during or after the infusion. Severe reactions including anaphylaxis are possible.

Cancer is also a possible risk after AAV gene therapies such as Fayuvi, because the vector DNA may become part of the body's own DNA. Contact your child's doctor and Ultragenyx Pharmaceutical at 1-888-756-8657 if your child develops cancer after treatment.

How long do Fayuvi side effects last?

Most side effects happen in the first few weeks and months after the single infusion.

Liver enzyme increases most often start within the first 14 days, although they began as late as 30 months after treatment in some children. They cleared up anywhere from 6 days to just over 3 years after they started. Low platelet counts usually occur within the first 2 weeks.

Your child will have blood tests weekly at first, then less often, until at least 6 months after the infusion.

This is not a complete list of side effects of Fayuvi. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Your child will have regular blood tests for at least 6 months after the infusion.

• Liver tests are done weekly for the first 2 weeks, then every 2 weeks until 2 weeks after the steroid medicine has been fully stopped. If liver enzymes are high, testing continues until they return to normal.
• Platelet counts are done weekly for the first 4 weeks, then monthly for 6 months.

Do not give your child any medicine, herbal product or supplement without checking with a healthcare professional first, since some can affect the liver.

Yes. For 3 months after the infusion, small amounts of the gene therapy leave the body in urine, stool and saliva. This is called vector shedding.

During this time:

• Seal used diapers in a disposable trash bag before putting them in the household trash.
• Wash hands well after any contact with your child's urine, stool or saliva.
• Tell family members and caregivers to do the same.

Fayuvi was tested in Study 1 (NCT02716246) in 17 children who received the approved dose. All were either 2 years old or younger at the time of treatment, or older than 2 with only mild to moderate developmental delay. Their thinking and learning skills were measured with a standard developmental test (the Bayley-III Cognitive Scale) and compared with 27 untreated children with MPS IIIA.

Between the ages of 2 and 5, children treated with Fayuvi gained thinking and learning skills, while untreated children lost them.

• Treated with Fayuvi: gained an average of 16 points
• Not treated: lost an average of 7.6 points
• Difference between the groups: 23.5 points, which was statistically significant

Researchers also measured heparan sulfate in spinal fluid. Levels dropped by more than half within the first month of treatment and remained about 57% below the starting level at 2 years. Of 16 children measured at 2 years, 15 kept a reduction of at least half.

Children in the studies have been followed for a median of about 4 years, with the longest follow-up close to 8 years. Because MPS IIIA is rare, these numbers come from small groups of children, and long-term results beyond this period are not yet known.

Fayuvi (rebisufligene etisparvovec-hopf) is made by Ultragenyx Pharmaceutical Inc. of Novato, California.