ZOLGENSMA targets the genetic root cause of SMA

As a gene therapy, ZOLGENSMA® (onasemnogene abeparvovec-xioi) is designed to target the genetic root cause of spinal muscular atrophy (SMA) by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene. ZOLGENSMA does not change or become a part of the child’s DNA.

To help you understand how this is possible, let’s look at how ZOLGENSMA works.

ZOLGENSMA targets the genetic root cause of SMA

As a gene therapy, ZOLGENSMA® (onasemnogene abeparvovec-xioi) is designed to target the genetic root cause of spinal muscular atrophy (SMA) by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene. ZOLGENSMA does not change or become a part of the child’s DNA.

To help you understand how this is possible, let’s look at how ZOLGENSMA works.

HOW ZOLGENSMA WORKS

See how ZOLGENSMA is changing SMA treatment

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NARRATOR: A dedicated team of scientists has developed a targeted approach for treating spinal muscular atrophy using a one-time-only gene therapy called ZOLGENSMA® (onasemnogene abeparvovec-xioi).

Gene therapy targets the genetic root cause of spinal muscular atrophy, or SMA, by replacing the function of the nonworking or missing gene that causes SMA, called the survival motor neuron 1 gene, or SMN1 gene. The SMN1 gene is very important because it’s the body’s main source for making SMN protein. SMN protein is used throughout the body, and it is essential to motor neuron cell survival.

Motor neuron cells are responsible for communicating with the muscles and telling them to work properly. In addition to the SMN1 gene, the body also has a backup gene called the SMN2 gene. People can have one or more copies of this backup gene. In a person with SMA, the SMN1 gene is not working properly or is missing and SMN protein cannot be made by the SMN1 gene. This is extremely serious because the SMN1 gene typically makes most of the SMN protein your body needs.

When the SMN1 gene cannot make SMN protein, the body relies on the SMN2 backup genes for this. Unfortunately, the SMN2 gene makes only about 10% of working protein compared to the protein produced by the SMN1 gene. That means that people with fewer SMN2 copies won’t make enough SMN protein. The severity of SMA is related to the number of copies of the SMN2 gene. SMA Type 1 is the most common type of SMA and is very serious. Individuals with SMA Type 1 typically have only two SMN2 backup genes.

Without enough SMN protein, motor neuron cells become weaker and weaker and eventually stop working, lose all function, and die. As a result, muscles can become so weak that eating, breathing, and moving become difficult, and the disease becomes life threatening.

Let’s learn how ZOLGENSMA works to treat SMA. It has two parts⁠—a gene and a vector⁠—and is made in a laboratory by scientists. First, let’s focus on the gene. It’s a new, working copy of a human SMN gene that replaces the function of the nonworking or missing SMN1 gene to restore SMN protein production in the motor neuron cells.

Now, let’s look at the vector. The vector used by ZOLGENSMA is made from a virus called adeno-associated virus 9, or AAV9. This type of virus does not make people sick. To make the vector, the DNA of the virus is removed. With the DNA gone, the fully functional SMN gene is placed inside the vector. The reason why ZOLGENSMA uses vectors to deliver the new genes is because they can travel quickly throughout the body to the motor neuron cells.

But how does ZOLGENSMA work? Once inside the body the vectors deliver new, working copies of SMN genes to the motor neuron cells. ZOLGENSMA sits inside the nucleus of the motor neuron cell and does not become part of the child’s DNA. Then, the new genes tell the motor neuron cells to start making SMN protein. This process happens repeatedly throughout the body with many vectors delivering new SMN genes to motor neuron cells so that SMN protein can be made in those cells.

Once the genes reach their destination, the vectors are broken down and excreted from the body.

ZOLGENSMA—changing the future of SMA treatment.

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Missing or nonworking SMN1 gene

1.

ZOLGENSMA targets the genetic root cause of SMA by replacing the function of the missing or nonworking gene, called the SMN1 gene. This gene is critical to making SMN protein.

SMN protein in a motor neuron

2.

SMN protein is essential to motor neuron cell survival. These cells control muscle function. Without SMN protein, motor neuron cells die, causing muscles to become so weak that breathing, eating, and moving become difficult, and the condition is likely to become life threatening.

New, working SMN gene inside a vector

3.

ZOLGENSMA is made up of a new, working copy of a human SMN gene that is placed inside a vector. A vector’s job is to take the new, working SMN gene to the motor neuron cells in the body.

DNA of an AAV9 (adeno-associated virus 9)  being removed and made into a vector

4.

The vector that delivers the SMN gene is made from a virus called adeno-associated virus 9, or AAV9. This type of virus does not make people sick. To make the vector, the DNA of the virus is removed so that the new SMN gene can be put inside. Vectors are used because they can travel throughout the body and deliver the new, working gene to the cells where it is needed.

Motor neuron cells making SMN protein

6.

With the motor neuron cells now able to make SMN protein, motor neuron cells that have not died may survive, function, and be maintained.

Important Safety Information

What is the most important information I should know about ZOLGENSMA?

  • ZOLGENSMA can cause acute serious liver injury. Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
  • Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function.

Important Safety Information

What is the most important information I should know about ZOLGENSMA?

  • ZOLGENSMA can cause acute serious liver injury. Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
  • Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function.
  • Contact the patient’s doctor immediately if the patient’s skin and/or whites of the eyes appear yellowish, or if the patient misses a dose of the corticosteroid or vomits it up.

What should I watch for before and after infusion with ZOLGENSMA?

  • Viral respiratory infections before or after ZOLGENSMA infusion can lead to more serious complications. Contact the patient’s doctor immediately if you see signs of a possible viral respiratory infection such as coughing, wheezing, sneezing, runny nose, sore throat, or fever.
  • Decreased platelet counts could occur following infusion with ZOLGENSMA. Seek immediate medical attention if a patient experiences unexpected bleeding or bruising.

What do I need to know about vaccinations and ZOLGENSMA?

  • Talk with the patient’s doctor to decide if adjustments to the vaccination schedule are needed to accommodate treatment with a corticosteroid.
  • Protection against respiratory syncytial virus (RSV) is recommended.

Do I need to take precautions with the patient’s bodily waste?
Temporarily, small amounts of ZOLGENSMA may be found in the patient’s stool. Use good hand hygiene when coming into direct contact with bodily waste for 1 month after infusion with ZOLGENSMA. Disposable diapers should be sealed in disposable trash bags and thrown out with regular trash.

What are the possible or likely side effects of ZOLGENSMA?
The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.

Indication

What is ZOLGENSMA?
ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time infusion into the vein. ZOLGENSMA was not evaluated in patients with advanced SMA.

The safety information provided here is not comprehensive. Talk to the patient’s doctor about any side effects that bother the patient or that don’t go away.

You are encouraged to report suspected side effects by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or AveXis at 833-828-3947.

Please see the Full Prescribing Information.