Overview of the ZOLGENSMA clinical studies

ZOLGENSMA® (onasemnogene abeparvovec-xioi) has been studied in 2 open-label clinical studies. One clinical study, called STR1VE, is ongoing, and the other clinical study, called START, has been completed. Children in both clinical studies had 2 copies of the SMN2 backup gene and experienced symptoms of spinal muscular atrophy (SMA) before 6 months of age. ZOLGENSMA was given through an IV infusion over 60 minutes. All patients received ZOLGENSMA and there was no placebo.

Overview of the ZOLGENSMA clinical studies

ZOLGENSMA® (onasemnogene abeparvovec-xioi) has been studied in 2 open-label clinical studies. One clinical study, called STR1VE, is ongoing, and the other clinical study, called START, has been completed. Children in both clinical studies had 2 copies of the SMN2 backup gene and experienced symptoms of spinal muscular atrophy (SMA) before 6 months of age. ZOLGENSMA was given through an IV infusion over 60 minutes. All patients received ZOLGENSMA and there was no placebo.

What is an open-label clinical study?

An open-label clinical study is one in which the patients and researchers know what treatment the patients are being given.


STR1VE clinical study (ongoing)

Overview

Twenty-two* patients with SMA took part in the phase 3 STR1VE clinical study. The average age of patients at the time of treatment was 3.7 months (range 0.5 to 5.9 months). Patients in this study received the therapeutic dose of ZOLGENSMA (the dose approved by the FDA).

Study results (as of the March 2019 data cutoff) when patients were an average of 13.8 months old

91% (20/22)

of patients were alive and did not need permanent breathing support, and were continuing in the study

  • 1 patient passed away at 7.8 months because of disease progression
  • 1 patient withdrew from the study at 11.9 months
  • About 95% (21/22) of patients have achieved a CHOP INTEND score of at least 40
    • 1 month after treatment, patients had an average increase of 6.9 points from where they started
50% (11/22) pie chart

could sit without help for at least 30 seconds

In the natural history of SMA Type 1:

  • About 25% of patients are alive without permanent breathing support at 14 months of age
  • Children who are 6 months of age or older do not score over 40 on the CHOP INTEND. Most score much worse and will see their scores decrease over time
  • Children are not able to sit without help
    • Unaffected children are typically able to sit without help at 9 months of age

The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.

START clinical study (completed)

Overview

Fifteen patients with SMA took part in the phase 1 START clinical study (for safety). Patients in the study were split into 2 groups. Three patients in group 1 received a low dose of ZOLGENSMA and 12 patients in group 2 received a high dose. The average age of patients at the time of treatment was 6.3 months (range 5.9 to 7.2 months) in group 1 and 3.4 months (range 0.9 to 7.9 months) in group 2.

Study results (24 months after treatment)

100% (12/12)

of patients in group 2 (high dose) were alive and did not need permanent breathing support

75% (9/12) pie chart

could sit without help for at least 30 seconds

17% (2/12) pie chart

could stand and walk without help

Of the 3 patients in group 1 who received a low dose of ZOLGENSMA:

  • 1 patient needed permanent breathing support
  • None of the patients were able to sit without help, or able to stand or walk

The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.

What is permanent breathing support?

Permanent breathing support was defined as tracheostomy or the need for continuous use of a machine to help breathe for at least 16 hours every day for 2 weeks or more in a child who did not have a severe and short-lasting, reversible illness or surgery.

What is natural history?

Natural history refers to the progression of a disease in a person over time without treatment.

What is the CHOP INTEND?

The CHOP INTEND, or the Children’s Hospital of Philadelphia (CHOP) Infant Test of Neuromuscular Disorders (INTEND), is a test used in the clinical study of ZOLGENSMA. The maximum test score is 64.


*

One patient was initially not part of the data set but will be included in the final data analysis.

Because of a change in how the dose was measured and the stability of stored ZOLGENSMA over time, the exact dose of ZOLGENSMA received by patients in this study is an estimate. Patients in group 2 received a dose between 1.1 x 1014 and 1.4 x 1014 vg/kg. The dose approved by the FDA is 1.1 x 1014 vg/kg. The dosage received by patients in the low-dose group was about one-third of the dosage received by patients in the high-dose group.

You need to act quickly and get a diagnosis because it’s a race against time with SMA Type 1.

Maria, mother of Louis

You need to act quickly and get a diagnosis because it’s a race against time with SMA Type 1.

Maria, mother of Louis

Understanding the risks of ZOLGENSMA

Elevated liver enzymes and liver injury

ZOLGENSMA could result in elevated liver enzymes and cause acute serious liver injury. An oral corticosteroid should be started the day before infusion with ZOLGENSMA. Your child’s doctor will monitor his or her liver function after treatment through blood tests and determine when to begin lowering the dose and eventually stopping the corticosteroid. You should contact your doctor immediately if your child’s skin and/or whites of the eyes appear yellowish, or if a dose of the corticosteroid is missed or vomited up.

Blood platelets

Decreased levels of blood platelets may occur after treatment with ZOLGENSMA. Your doctor will monitor blood platelet levels through blood tests before and after treatment. Seek medical attention in the event of any unexpected bleeding or bruising.

Vaccination

You should talk with your doctor to decide if adjustments to the vaccination schedule should be made during corticosteroid use. Protection against respiratory syncytial virus (RSV) is recommended.

Respiratory infections

Viral respiratory infection before or after treatment with ZOLGENSMA infusion could lead to more serious complications. You should contact your doctor immediately if your child exhibits any of the following symptoms: coughing, wheezing, sneezing, runny nose, sore throat, or fever.

Important Safety Information

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

  • Liver enzymes could become elevated and cause 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?

  • Liver enzymes could become elevated and cause 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.