Zanvastro

Zanvastro (zilganersen) is a prescription medicine used to treat Alexander disease in babies, children, and adults. It is a disease-modifying treatment, which means it works on the cause of the disease to slow how quickly it gets worse. It is not a cure, and it does not repair damage already done.

It is the first medicine approved by the U.S. Food and Drug Administration (FDA) for this condition.

Alexander disease is an ultra-rare genetic brain disorder. It is caused by changes (variants) in a gene called GFAP. These changes make brain cells produce too much of a protein called glial fibrillary acidic protein, or GFAP. The buildup of this protein damages the brain over time and slowly affects movement, swallowing, speech and thinking.

Zanvastro works by lowering the amount of GFAP protein the body makes, so it works on the cause of the disease rather than only easing symptoms.

Zanvastro is given as an injection into the fluid around the spinal cord (an intrathecal injection), usually once every 3 months. A healthcare provider gives each dose in a clinic or hospital.

Zanvastro FDA approval was granted on September 3, 2026, after positive results from study 1 (NCT04849741). It is made by Ionis Pharmaceuticals.

Zanvastro is FDA-approved to treat Alexander disease in children and adults. There is no age limit in the approved label, so it can be used in infants, older children, teenagers, and adults.

Zanvastro is not a cure. In studies, it slowed the loss of walking speed, and in young children it improved some movement skills. It does not reverse damage that has already happened.

Zanvastro is an antisense oligonucleotide (a short, lab-made strand of genetic material designed to attach to a specific target in the cell).

In Alexander disease, the GFAP gene sends out too many instructions to build GFAP protein. Zanvastro attaches to those instructions, called GFAP pre-mRNA, and causes them to break down. Fewer instructions means less GFAP protein is made, which is expected to reduce the protein buildup that drives the disease.

In the main study, people taking Zanvastro had GFAP levels in their blood that were 33.6% lower than the control group after 5 doses (at week 61).

Zanvastro is given by a healthcare professional as an intrathecal injection, which means the medicine goes into the fluid that surrounds the spinal cord. It is given through a lumbar puncture (a needle placed into the lower back, sometimes called a spinal tap).

Here is what usually happens at each visit:

• The medicine is mixed with a special fluid, called artificial cerebrospinal fluid, before it is given.
• You may be offered sedation or a numbing medicine, depending on your age and how you are feeling.
• An imaging scan may be used to help guide the needle.
• A small amount of your own spinal fluid is removed first, roughly the same amount as the dose being given.
• The dose is then injected slowly over 1 to 3 minutes.

The person giving the injection should be experienced in performing lumbar punctures. Your care team will check beforehand for anything that could make a lumbar puncture riskier for you.

There are no contraindications for Zanvastro, which means there is no group of people who must avoid it entirely. The main safety issue to know about is aseptic meningitis.

Aseptic meningitis

Zanvastro can cause aseptic meningitis. This is swelling of the layers that cover the brain and spinal cord that is not caused by an infection. It is also called chemical meningitis or drug-induced aseptic meningitis.

Contact your healthcare provider straight away if you or your child develops symptoms such as:

• Headache that will not go away
• Stiff neck
• Fever
• Nausea or vomiting
• Sensitivity to light
• Confusion or unusual sleepiness

In the main study, one person had a serious reaction of aseptic meningitis. It came back later in the study, so treatment was paused and a steroid medicine (intravenous dexamethasone) was given before the next dose. That person was able to stay on treatment.

Some people also had a rise in white blood cells in their spinal fluid without any symptoms. Your care team may check your spinal fluid for this.

Pregnancy and breastfeeding

There is no information on the use of Zanvastro in pregnant women, so the risk to an unborn baby is not known. In animal studies, zilganersen did not harm the development of the fetus at doses about 6 times the human dose.

It is not known whether Zanvastro passes into breast milk, or whether it affects a breastfed baby or milk supply. Talk with your provider about the benefits of breastfeeding alongside your need for treatment.

Older adults

Zanvastro has not been studied in people aged 65 years and over. It is not known whether it works differently in this age group.

Kidney and liver problems

Mild kidney or liver problems did not meaningfully change how zilganersen behaves in the body. Zanvastro has not been studied in people with moderate or severe kidney or liver problems, or in people with end-stage kidney disease.

The most common side effects of Zanvastro are vomiting, back pain, cough, headache and post-lumbar puncture syndrome (headache and other symptoms that can follow a spinal tap). Each of these affected more than 25% of people in the main study.

The table below shows side effects that happened in at least 10% of people treated with Zanvastro, and at least 10% more often than in the control group.

Some side effects come from the injection procedure itself rather than the medicine. Back pain and post-lumbar puncture syndrome are common after any lumbar puncture.

Other effects seen with Zanvastro:

• Raised white blood cells in spinal fluid (pleocytosis). This happened in 7 of 24 people (29%) treated with Zanvastro after the first 2 to 4 doses, compared with 3 of 17 people (18%) in the control group.
• Antibodies to the medicine. About 28% of treated people developed antibodies against Zanvastro. These did not appear to change how safe or effective the medicine was, although the number of people studied was small.

Side effects in babies under 2 years old are expected to be similar to those in older children.

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

No drug interactions have been identified for Zanvastro. No drug interaction studies have been done in people.

Laboratory testing suggests interactions are unlikely. Zilganersen is not broken down by the liver enzymes (cytochrome P450) that many medicines rely on, and it does not block or speed up those enzymes. It also does not interfere with drug transporters or with medicines that bind strongly to blood proteins.

Even so, tell your provider about all the medicines, vitamins and herbal products you take.

Zanvastro was approved based on one main study (Study 1, NCT04849741) in children and adults with Alexander disease. Everyone in the study had the diagnosis confirmed by symptoms, brain MRI and genetic testing.

The main part of the study included 49 people aged 2 to 65 years. A separate open-label part included 4 children under 2 years old. People were randomly assigned 2:1 to receive Zanvastro or to act as controls, and treatment continued for 60 weeks before the study opened up.

The main measure was walking speed on the 10-meter walk test after 61 weeks, in people aged 5 years and over who had recent problems with movement.

• Walking speed dropped by 2.1% in the Zanvastro 50 mg group.
• Walking speed dropped by 35.4% in the control group.
• The difference between the groups was 33.3% in favor of Zanvastro (95% confidence interval 1.44 to 65.25; p = 0.041).

In other words, people on Zanvastro largely held on to their walking speed over a year, while the control group declined.

In the 4 children aged 2 to 4 years who were treated, movement skills such as standing, walking, running and jumping improved on a scale called the GMFM-88. The 3 children in the control group got worse over the same period.

The recommended dose of Zanvastro is 50 mg given intrathecally every 3 months. The dose is the same for everyone, including infants, children, and adults.

This preparation takes several careful steps, including removing an exact amount of the fluid based on your age, so it is always done by a trained healthcare professional following the instructions supplied with the medicine.

The amount of liquid injected does change with age, because younger children have less spinal fluid:

Zanvastro comes as a carton holding one vial of medicine (56 mg in 2.8 mL) and one vial of diluent (21 mL). The two are combined to make a single dose.

What if a dose is missed?

If a dose of Zanvastro is missed, it should be given as soon as possible. After that, dosing carries on every 3 months counting from the date of the most recent injection.

Zanvastro is stored and prepared by healthcare professionals, not at home. Vials are kept in a refrigerator between 2°C and 8°C (36°F and 46°F) in the original carton to protect them from light. Vials may be kept at room temperature up to 30°C (86°F) in the carton for up to 14 days, and are thrown away if not used in that time. The vials must not be frozen.