Spinal muscular atrophy (SMA) is a genetic condition that is passed down through families. It leads to muscle weakness, which may affect everyday functions such as head movement, sitting without help, walking, swallowing, or breathing. SMA is divided into types based on when symptoms first appear. It may be called infantile if the symptoms first appear in infants, juvenile if they first appear in children, or adult-onset if they first appear in adults.
Itvisma (onasemnogene abeparvovec-brve) is a type of gene therapy that is injected into the area around the spine to treat SMA in children and adults who have a problem with a gene called survival motor neuron 1 (SMN1).
How Does Itvisma Work for Spinal Muscular Atrophy?
SMA usually happens because of a problem with a gene called SMN1. Normally, the SMN1 gene makes a protein (called the SMN protein) that is needed to keep the nerve cells that help control your muscles healthy. People with SMA do not make enough of this protein, which causes the nerve cells to gradually weaken and eventually die.
Itvisma works by using a harmless, modified virus to deliver a healthy copy of the SMN1 gene into the motor nerve cells. This virus cannot multiply or cause infection. Once the healthy copy of the SMN1 gene is inside the cell, it tells the cell to make the SMN protein. This helps replace the SMN protein that the body cannot make on its own.
By restoring SMN protein levels in the motor nerve cells, Itvisma is expected to help these cells survive and work better, which may improve muscle strength and slow or prevent further muscle weakness in people with SMA.
How Was Itvisma Studied for SMA?
The safety and effectiveness of Itvisma for SMA were tested in the STEER study. It included 126 people with SMA aged 2-17 years who had never had any treatment for their condition. People in the study were able to sit on their own but were not able to walk without help. Study participants were either given a single injection of Ivitsma into the area around their spine or a sham injection that did not contain any medicine. People who got Ivitsma also took a daily corticosteroid, which was started 24 hours before the injection, continued for about 30 days, and then tapered. People who got the sham injection took a daily placebo (containing no medicine) in the same way.
The main outcome that the researchers were interested in was the change in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score from the beginning of the study to about one year later. This change was compared between people who got Itvisma and those who got a sham injection. The HFMSE is a scale that measures muscle ability over time. The highest score you can get is 66. Higher scores mean greater motor function or ability. An improvement of at least 1.5 points is considered meaningful.
What Were the Characteristics of People in the Study?
Some of the main details of the people who took part in the study are described below:
- Their average age was 6 years.
- About half (49%) of people were male.
- 59% were Asian, 11% were White, 7% were Black or African American, 6% were American Indian or Alaska Native, and 18% reported their race as unknown.
- Before the study, the highest level of muscle ability was reported and is described below:
- Sitting without help (52%)
- Standing with help (26%)
- Walking with help (19%)
- Standing without help (2%)
- Before the study, HFMSE scores ranged from 1 to 42.5, with an average HFMSE score of about 18. This means muscle function was quite variable, but their muscles were not working very well before receiving treatment.
What Benefits Were Seen?
Itvisma seems to improve HFMSE scores better than sham injections. The results of the STEER study are presented below.
Itvisma (75 people) | Sham (51 people) | |
|---|---|---|
| Mean change from baseline HFMSE score* | 2.39 | 0.51 |
| Difference* | 1.88 | |
*These data are based on calculations that adjust for differences between groups, known as least squares (LS) means. It is another way to compare results and may give a more accurate comparison than raw data.
In summary, after about one year, people who got a single injection of Itvisma had a larger improvement in HFMSE scores than those who got a sham injection. This means that Itvisma seems to improve motor function in children with SMA better than sham injections.
Your results may differ from what was seen in clinical studies.
Who Should Not Use Itvisma?
There is another medicine called Zolgensma that contains the same ingredient as Itvisma. However, Zolgensma is given as an infusion through a vein (IV) and is used in people with SMA who are younger than 2 years. If you have ever been given a dose of Zolgensma, you should not use Itvisma.
If you have had a recent infection or are currently sick, you should not get Itvisma until your infection is better.
What Lab Tests Do I Need Before Receiving Itvisma?
Before you get your dose of Itvisma, there are certain lab tests you will need to have checked. These lab tests are done to make sure it is safe to use Itvisma. Some of the lab tests you might have done are described below:
- Liver function tests. Itvimsa can cause serious problems with your liver, and people who already have liver damage may be at a higher risk of these side effects.
- Complete blood count. Itvisma can lower your level of platelets (cell fragments in your blood that help your blood clot), causing a condition called thrombocytopenia. Itvisma can also cause other problems with your blood cells.
- Creatinine. This blood test checks to see how well your kidneys are working.
- Antibody testing. Your health care provider will test you for antibodies to the virus that is used to make Itvisma, which is called adeno-associated virus type 9 (AAV9). Most people are naturally exposed to AAV9 in their environment throughout their lives, and their immune systems produce antibodies to fight off infection. If you have high levels of AAV9 antibodies before treatment, Itvisma may not work as well.
These tests may be repeated at different times after you get your dose of Itvisma. You may also need tests other than those described above.
Is There Anything Else That I Should Do Before My Dose?
Your health care provider will likely check to make sure that your vaccinations are up to date. It is important to be up to date on routine vaccinations to lower your risk of serious infections after getting Itvisma. Seasonal vaccination against the respiratory syncytial virus is also recommended.
Starting one day (24 hours) before your scheduled dose of Itvisma, you should start taking a daily dose of a corticosteroid. Common examples of corticosteroids are dexamethasone, methylprednisolone, prednisolone, or prednisone. This medicine is given to lower your risk of developing serious liver problems from Itvisma.
How Is Itvisma Given?
Itvisma is given as an intrathecal injection, meaning it is injected into the fluid around your spinal cord. It is usually given at a treatment center by health care providers who know how to give these shots.
Itvisma is injected once as a single dose. Everyone who is given Itvisma will get the same dose.
After your dose, you will continue to take a daily corticosteroid for about one month. After that, if your liver function tests are normal, your health care provider may gradually lower your dose of the corticosteroid until you stop taking it completely. This is called tapering the dose. If your liver test results are high, you will likely continue with your current corticosteroid dose until your liver tests return to normal before tapering the dose. Do not change your dose or stop taking your corticosteroid without talking to your health care provider first.
How Fast Does Itvisma Start to Work?
In the STEER study, people who were treated with Itvisma saw improvements in their HFMSE scores as early as four weeks after their dose of Itvisma. Some people saw further improvements in muscle function over the course of the study. Note that your results may differ from those seen in the STEER study.
How Can I Prevent and Manage Side Effects?
The most common side effects that happen in people who use Itvisma include infections in the nose or throat, sore throat, or common cold symptoms, vomiting, fever, and headache.
To help prevent infections, be sure to wash your hands frequently. Do not touch your face with your hands. Do not drink out of cups or glasses that someone else has used. If you become sick, contact your health care provider if your symptoms do not improve in one to two weeks or if they are severe.
To help prevent headaches, be sure to get enough sleep at night, eat regular meals, drink plenty of water, and limit stress.
If you throw up, make sure to stay hydrated by drinking plenty of clear fluids. Eating bland, low-fat foods like crackers, toast, and rice may also help settle your stomach.
These are not all of the possible side effects. Talk to your health care provider if you have symptoms that bother you. In the U.S., you can report side effects to the FDA at https://www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at https://www.health.gc.ca/medeffect or by calling 866-234-2345.
What Do I Need to Know About Contraception and Egg or Sperm Donation?
If you can get pregnant, use an effective method of contraception and avoid egg donation for at least six months after getting your dose of Itvisma.
If you have a partner who can get pregnant, use a barrier method of contraception and avoid sperm donation for at least three months after your dose of Itvisma. Examples of barrier methods of contraception are listed below:
- Cervical caps or shields
- Condoms
- Contraceptive sponges
- Diaphragms
- Spermicide
Is There Any Cost Assistance Available?
The drugmaker offers a copay assistance program that may help you afford Itvisma if you are eligible. Your health care provider will help you get started. After your health care provider prescribes Itvisma, a case coordinator will help you with your insurance benefits. You can find out more by calling 855-441-4363 or visiting the drugmaker’s website at itvisma.com/support/novartis-patient-support.
