Symptomatic clinical study results

SYMPTOMATIC STUDY RESULTS

PRESYMPTOMATIC STUDY RESULTS

The clinical studies of ZOLGENSMA® (onasemnogene abeparvovec-xioi), STR1VE and START, enrolled patients who showed symptoms (symptomatic) of spinal muscular atrophy (SMA) before treatment. In addition, an ongoing 15-year long-term follow-up (LTFU) observational study enrolled 13 of the patients from the START study. All of these studies have shown that ZOLGENSMA helps stop the progression of SMA.

STR1VE study details

The purpose of the STR1VE study was to establish the efficacy and safety of ZOLGENSMA. The results reported below are from the end of the STR1VE study. The study enrolled 22* symptomatic patients diagnosed with SMA Type 1, who had 2 copies of the SMN2 backup gene, and were 6 months of age or younger at the time of IV infusion.

  • The average age at dosing was 3.7 months (range 0.5-5.9 months)
  • Patients received the therapeutic dose of ZOLGENSMA (dose approved by the FDA)
  • Patients were followed through their 18 months of age study visit

*One patient was initially classified as presymptomatic but was later confirmed to be symptomatic and was included in the final clinical study findings.

STR1VE results

Increased event-free survival

At the 14 months of age study visit,

(20/22)* of patients were alive and did not need permanent breathing support

In the natural history of SMA Type 1 (children who haven’t received treatment), about 25% of children are alive without permanent breathing support at 14 months of age.

  • 1 patient passed away at 7.8 months of age from causes unrelated to treatment
  • 1 patient withdrew from the study at 11.9 months of age and required permanent ventilation at 11 months of age prior to leaving the study

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

What is an event?

Event is defined as death, the need for permanent ventilatory support (such as tracheostomy), or the need for respiratory assistance (not due to illness or surgery) for 16 hours or more a day for at least 14 days.

Helped patients achieve new motor milestones at 18 months of age

Sitting independently

(13/22) of patients could sit without support for at least 30 seconds

In the natural history of SMA Type 1, patients are never able to sit independently.

*One patient achieved the milestone of sitting independently for 30 seconds or more at 16 months of age, but this milestone was not reconfirmed at the 18 months of age study visit (end of study).

Head control

At the start of the study, 2/22 patients already had head control prior to dosing and maintained control.

Standing and walking

1 patient
could stand and walk independently

This patient was treated at 1.1 months of age and could stand at 14.7 months and walk at 15.3 months of age.

Helped patients maintain the ability to thrive

In STR1VE, the ability to thrive is a measurement of 3 components related to feeding.

Icon of baby bottle

55%

(12/22) ability to swallow thin liquids measured by a swallowing test

Icon of plate with fork and knife

86%

(19/22) freedom from non-oral feeding support (G-tube)

Icon of scale

64%

(14/22) ability to maintain weight that’s consistent with age*

(9/22) of patients met all 3 components of ability to thrive at 18 months of age

In the natural history of SMA Type 1, nearly all patients required feeding support at 12 months of age.

*≥3rd percentile for ages and gender.

Helped patients stay free of respiratory and feeding support

(15/22) of patients did not need respiratory support during the study

(15/22) of patients did not need feeding support during the study*

In the natural history of SMA Type 1, the majority of patients required respiratory and feeding support.

*Four patients had temporary feeding support once during the study (lasting 6 to 91 days); 3 patients needed ongoing feeding support at 18 months of age or upon withdrawing from the study; 4 patients required Trilogy BiPAP respiratory support at 18 months of age.

What is respiratory support?

If a child needs respiratory support, it means he or she receives help breathing through the use of ventilator equipment, such as a bilevel positive airway pressure (BiPAP) machine.

What is feeding support?

If a child needs feeding support, it means he or she receives additional nutrition through ways other than eating by mouth, like a gastrostomy tube (G-tube).

Helped patients improve and maintain motor function

Patients had improvement in motor function as assessed by CHOP INTEND, or the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. This test was created to measure the motor development of children with SMA Type 1. The CHOP INTEND scale ranges from 0 to 64, with higher scores indicating better function.

In the natural history of SMA Type 1, children 6 months of age or older almost never achieve scores higher than 40.

By the end of the trial:

95%

(21/22) of patients achieved a score of 40 or more

64%

(14/22) of patients achieved a score of 50 or more

23%

(5/22) of patients achieved a score of 60 or more

START study details

START results

START LTFU study details

START LTFU results

“My expectations were for Matteo to be as healthy as possible. That maybe he could sit up, and maybe he could eat by himself. Something that was not an option with SMA.”

Derwin, father of Matteo

See results from the presymptomatic SMA study

See results

See the safety data of ZOLGENSMA in clinical studies

See ZOLGENSMA safety

Important Safety Information

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

  • ZOLGENSMA can increase liver enzyme levels and cause acute serious liver injury or acute liver failure which could result in death.
  • 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 increase liver enzyme levels and cause acute serious liver injury or acute liver failure which could result in death.
  • 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, if the patient misses a dose of corticosteroid or vomits it up, or if the patient experiences a decrease in alertness.

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

  • Infections before or after ZOLGENSMA infusion can lead to more serious complications. Caregivers and close contacts with the patient should follow infection prevention procedures. Contact the patient’s doctor immediately if the patient experiences any signs of a possible 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 the patient experiences unexpected bleeding or bruising.
  • Thrombotic microangiopathy (TMA) has been reported to generally occur within the first two weeks after ZOLGENSMA infusion. Seek immediate medical attention if the patient experiences any signs or symptoms of TMA, such as unexpected bruising or bleeding, seizures, or decreased urine output.

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 influenza and respiratory syncytial virus (RSV) is recommended and vaccination status should be up-to-date prior to ZOLGENSMA administration. Please consult the patient’s doctor.

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 patient body waste for one 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 a 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 Novartis Gene Therapies, Inc. at 833-828-3947.

Please see the Full Prescribing Information.