Hunter syndrome, also known as mucopolysaccharidosis II (MPS II), is a rare inherited condition that mainly affects boys. It causes certain substances to build up in the body, leading to damage to multiple organs.
Hunter syndrome is progressive, which means it gets worse over time. In many children, symptoms begin early in life. Hunter syndrome can present in two main forms:
- In the non-neuronopathic form, symptoms mainly affect the body, and mental function is usually normal or only slightly affected.
- About two-thirds of people with this condition have a more severe form that affects the brain, called neuronopathic MPS II. It can lead to a gradual loss of thinking and learning abilities, often starting between the ages of 2 and 4.
Hunter syndrome can also cause a range of physical symptoms, such as frequent respiratory infections, a runny nose, hearing loss, enlarged liver and spleen, and problems with the joints, bones, and heart.
Standard treatments, called enzyme replacement therapy, have helped treat some physical symptoms of Hunter syndrome. However, these treatments cannot reach the brain because they do not cross the blood-brain barrier, a protective layer that controls what enters the brain. As a result, they may not address the neurologic (brain-related) symptoms of the disease.
Avlayah (tividenofusp alfa-eknm) is a newer type of enzyme replacement therapy designed to overcome this limitation. It is designed to cross the blood-brain barrier, allowing it to reach both the body and the brain. The FDA approved Avlayah in March 2026 to treat neurologic symptoms in children with Hunter syndrome who do not yet have advanced neurologic problems and weigh at least 5 kilograms (11 pounds).
Below is a closer look at how Avlayah works for Hunter Syndrome, what benefits were seen in studies, and its possible side effects.
How Does Avlayah Work for Hunter Syndrome?
In people with Hunter syndrome, the body is missing or does not properly make an enzyme called iduronate 2-sulfatase (IDS). This enzyme normally helps break down certain complex sugars called glycosaminoglycans (GAGs). When IDS is not working properly, or when the body does not have enough IDS, these sugars build up inside cells. Over time, this buildup can damage many parts of the body, including the brain.
Avlayah works by replacing the IDS enzyme. It provides a working version of the enzyme so the body can start breaking down these sugars again, which reduces their buildup.
This medicine has a special feature that helps it reach more areas of the body, including the brain. It attaches to a protein called the transferrin receptor, which helps carry the medicine across the blood-brain barrier. Once inside cells, Avlayah is delivered to a part of the cell called the lysosome, where it can do its job of breaking down the accumulated sugars. This may improve how cells and organs function over time.
How Is Avlayah Given?
Avlayah is given as an intravenous (IV) infusion, which means it is delivered into a vein through a needle. It is usually given once a week.
The exact dose of Avlayah is based on body weight. At the start of treatment, Avlayah is given in lower doses that may be gradually increased over time. This gradual approach helps reduce the chance of infusion-related side effects.
Each infusion is done slowly over several hours, typically over four hours, depending on how well it is tolerated. In some cases, the infusion may take up to eight hours if it needs to be given more slowly. If a reaction happens during the infusion, the health care provider may pause the infusion, slow the rate, or adjust the dose. They will monitor closely and treat symptoms as needed.
Avlayah is first given in a health care setting, where your child can be closely monitored. This is important because some people may have side effects during or after an infusion, including allergic reactions. Your child may be given medicines before the infusion (such as antihistamines, corticosteroids, and/or fever-reducing medicines) to help prevent these reactions.
If the treatment is tolerated well, home infusions of Avlayah may eventually be possible under the supervision of a health care provider.
How Was Avlayah Studied for Hunter Syndrome?
Avlayah was studied in a 24-week clinical trial involving children and adolescents with Hunter syndrome. The study took place across several sites in North America and Europe. Parents or guardians provided consent for children to take part. Children could enter the study if they had a confirmed diagnosis of Hunter syndrome. This could include a form that affects the brain (neuronopathic MPS II) or a form that mainly affects the body (non-neuronopathic MPS II).
A total of 47 children joined the study. The median (middle value) age was 5 years, with participants ranging in age from 3 months to 13 years. Most (70%) were 4 years or older. All participants were male. Most (57%) were White, 9% were Asian, 9% were Black, 17% did not report their race or identified as an unknown race, and a few participants identified as other or more than one race. Most (81%) were not Hispanic or Latino, 15% were Hispanic or Latino, and 4% did not report their ethnicity.
Most children (94%) had a form of the disease that affects the brain (neuronopathic MPS II), while a small number (6%) had the non-neuronopathic form.
Some children (68%) had received other enzyme replacement therapy (ERT) before joining the study, while others (32%) had not. Among those who had previously received ERT, the median age when they started treatment was 3 years, and many had been on ERT for more than 2 years before switching to Avlayah.
All participants received Avlayah as a once-weekly IV infusion. The main part of the study lasted 24 weeks. Longer-term studies are ongoing to continue monitoring the safety and effectiveness of Avlayah over time.
The main goal of the study was to examine the safety of Avlayah over the first 24 weeks of treatment. Another key goal was to measure a certain substance in the body (heparan sulfate) that builds up in people with Hunter syndrome. They compared levels before treatment and after 24 weeks to see if the buildup decreased.
What Did the Study Results Show?
All study participants experienced at least one side effect during treatment, most commonly reactions during or shortly after the infusion. A small number of participants had serious side effects, but all were able to continue treatment. (See the next section below for more details about Avlayah side effects.)
Of the 44 people who had measurements after 24 weeks of treatment, heparan sulfate levels decreased by about 91% on average in the cerebrospinal fluid (the fluid around the brain and spinal cord). Individual results ranged from about a 72% to 98% decrease.
Before treatment, none of the children had heparan sulfate levels in the normal range. After 24 weeks, 93% of children had levels that were similar to those seen in children without Hunter syndrome.
These results suggest that Avlayah was able to reach the brain and reduce the buildup of certain substances in children with Hunter syndrome.
Your results may differ from what was seen in clinical studies.
The FDA approved Avlayah through a pathway called accelerated approval. This pathway allows earlier access to medicines for serious conditions when early study results show improvement in an important biomarker.
In this case, the biomarker was heparan sulfate levels in the cerebrospinal fluid, which may reflect buildup in the brain. More studies are needed to confirm whether lowering these levels leads to meaningful improvements in symptoms of Hunter syndrome.
What Should I Know About the Possible Side Effects of Avlayah?
Avlayah can cause side effects, including serious reactions. Your health care provider will monitor for reactions during each infusion, but there are also things you can watch for at home.
Watch for signs of allergic reactions. Serious allergic reactions, including anaphylaxis, can happen with Avlayah. These reactions may occur early in treatment or even after your child has been on the medicine for a while. Take any pretreatment medicines as directed.
Get emergency medical help right away if your child has symptoms such as trouble breathing or wheezing, fast heartbeat or fainting, hives or a bad rash, swelling of the lips, tongue, or vomiting.
Be aware of infusion-related reactions. Some side effects can happen during the infusion or within about a day after. These are called infusion-related reactions. About 87% of study participants had at least one infusion-related reaction, making this the most common side effect of Avlayah. These reactions seem more common in the first few weeks of treatment and may become less likely over time. Make sure that any pre-infusion medicines (such as antihistamines or fever reducers) are taken as directed.
Common symptoms of infusion-related reactions may include:
Tell your child’s care team right away if you notice these symptoms. If it starts during the infusion, they may slow, pause, or stop the infusion, depending on how severe the symptoms are and how quickly they go away.
Watch for signs of anemia. Avlayah can lower red blood cell count, especially in the first few months of treatment. In the study, about half of the children had anemia, though most cases improved over time. Contact your health care provider if your child has unusual tiredness or pale-looking skin. Your child will have blood tests to monitor for anemia, and treatment such as iron supplements may be recommended if needed.
Stay in close contact with your child’s care team. Keep all scheduled appointments for infusions and monitoring. Report any new or worsening symptoms right away. Follow instructions about medicines given before or after infusions. Your child’s health care provider can adjust the infusion rate or dose, or they may prescribe supportive treatments to help manage side effects and keep treatment as safe as possible.
Is There Any Cost Assistance Available?
A cost assistance program is available from Denali Therapeutics, the maker of Avlayah. This program may help lower what you pay for treatment.
Eligibility depends on factors such as your insurance coverage or whether you are uninsured. Visit the program website to check if you qualify for copay savings. You can also call 844-365-4365 to speak with a representative about patient support options.