Results from the ongoing presymptomatic SMA study of ZOLGENSMA

PRESYMPTOMATIC STUDY RESULTS

The purpose of the SPR1NT study was to evaluate the efficacy and safety of ZOLGENSMA® (onasemnogene abeparvovec-xioi) in patients younger than 6 weeks of age and showing no symptoms (presymptomatic) of spinal muscular atrophy (SMA). The study enrolled 29 presymptomatic patients diagnosed with SMA who had 2 or 3 copies of the SMN2 backup gene.

SPR1NT study

The purpose of the SPR1NT study was to evaluate the efficacy and safety of ZOLGENSMA in patients younger than 6 weeks of age and showing no symptoms (presymptomatic) of SMA.

SPR1NT participants

The study enrolled 29 presymptomatic patients diagnosed with SMA who had 2 or 3 copies of the SMN2 backup gene. The average age at treatment:

  • 2 copies of SMN2 (14 patients): 20.6 days (range 8-34 days)
  • 3 copies of SMN2 (15 patients): 28.7 days (range 9-43 days)
  • Patients received the therapeutic dose of ZOLGENSMA (dose approved by the FDA)

The number of copies of the SMN2 backup gene is typically related to the severity of SMA. Children with SMA Type 1 typically have 1 to 3 (most commonly 2) copies of the SMN2 backup gene and children with SMA Type 2 most commonly have 3 copies of the SMN2 backup gene.

SPR1NT results

The following results are as of December 2019 (this study is ongoing). The average (mean) age of patients at the last visit before data were collected:

  • 2 copies of SMN2 (14 patients): 11.2 months
  • 3 copies of SMN2 (15 patients): 9.7 months
2 copies of SMN2 icon

SPR1NT study results: 2 copies SMN2 backup gene

ZOLGENSMA helped patients reach age-appropriate milestones

The Bayley-III and WHO-MGRS (World Health Organization Multicentre Growth Reference Study) are measurement scales used to assess motor function in the SPR1NT study. The Bayley-III is the most common tool used to determine children’s motor skills compared to what is expected for a “typical” developing child. The WHO-MGRS provides a timeline for assessing motor milestone development in “unaffected” children.

In the natural history of SMA Type 1, patients are not able to sit, stand, or walk independently.

57%

(8/14) of patients sat without assistance (30 seconds or more) as measured by the Bayley-III

  • 7/8 patients achieved sitting without support within an age-appropriate time according to WHO-MGRS definition
Child sitting up icon

100%

(6/6) of the remaining patients were still within the age-appropriate WHO developmental window for sitting without support

Most unaffected children can sit without support between 4 and 9 months of age (WHO-MGRS).

21%

(3/14) of patients stood without assistance (10 seconds or more) as measured by WHO-MGRS

  • 2/3 patients achieved this milestone within an age-appropriate time
Child standing icon

91%

(10/11) of the remaining patients were still within the age range of when unaffected children should achieve this milestone

Most unaffected children can stand without support between 7 and 17 months of age (WHO-MGRS).

29%

(4/14) of patients walked without assistance (5 steps or more) as measured by WHO-MGRS

  • 3/4 patients achieved this milestone within an age-appropriate time
Child walking icon

100%

(10/10) of the remaining patients were still within the age range of when unaffected children should achieve this milestone

Most unaffected children can walk without assistance between 8 and 18 months of age (WHO-MGRS).
Learn more about the natural history of children with SMA Type 1 and Type 2

ZOLGENSMA increased overall motor function

In the natural history of SMA Type 1, children who are 6 months of age or older do not score higher than 40. Most children score much worse and will see their scores decrease over time.

CHOP INTEND is the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and was created to measure the motor development of children with SMA Type 1.

ZOLGENSMA increased motor scores

In presymptomatic patients treated with ZOLGENSMA, 50% (7/14) achieved motor scores within the age-appropriate range for unaffected patients. These scores include the ability to achieve skills such as sitting, standing, or walking with assistance. Each line in the graph represents an individual patient.

Graph of increased motor scores (SPR1NT, 2 copies) with ZOLGENSMA® (onasemnogene abeparvovec-xioi)
In the natural history of SMA Type 1, untreated children with 2 copies of the SMN2 backup gene would not achieve skills on this scale.

50%

(7/14) achieved motor scores within the age-appropriate range for unaffected patients

100%

(14/14) had fine motor skills similar to unaffected children of the same age

Bayley-III motor scores in patients with 2 copies of SMN2 and >1 study visit.

3 copies of SMN2 icon

SPR1NT study results: 3 copies SMN2 backup gene

ZOLGENSMA helped patients reach age-appropriate milestones

27%

(4/15) of patients stood without assistance (3 seconds or more) as measured by Bayley-III

  • 4/4 patients achieved this milestone within an age-appropriate time
Child standing icon

100%

(11/11) of the remaining patients were still within the age-appropriate WHO developmental window for this milestone

Most unaffected children can stand without support between 7 and 17 months of age (WHO-MGRS).

13%

(2/15) of patients walked without assistance (5 steps or more) as measured by Bayley-III

  • 2/2 patients achieved this milestone within an age-appropriate time
Child walking icon

100%

(13/13) of remaining patients were still within the age range of when unaffected children should achieve this milestone

Most unaffected children can walk without assistance between 8 and 18 months of age (WHO-MGRS).

60%

(9/15) of patients stood with assistance (10 seconds or more) as measured by WHO-MGRS

  • 8/9 patients achieved this milestone within an age-appropriate time
Child standing with assistance from table icon

100%

(6/6) of the remaining patients were still within the age range of when unaffected children should achieve this milestone

Most unaffected children can stand with assistance between 5 and 11 months of age (WHO-MGRS).
Learn more about the natural history of children with SMA Type 2 and Type 3

ZOLGENSMA increased motor scores

In presymptomatic patients treated with ZOLGENSMA, 100% (15/15) achieved motor scores within the age-appropriate range for unaffected patients. These scores include the ability to achieve skills such as sitting, standing, or walking with assistance. Each line in the graph represents an individual patient.

Graph of increased motor scores (SPR1NT, 3 copies) with ZOLGENSMA® (onasemnogene abeparvovec-xioi)

100%

(15/15) had gross motor skills similar to unaffected children of the same age

93%

(14/15) had fine motor skills similar to unaffected children of the same age

Bayley-III motor scores in patients with 3 copies of SMN2 and >1 study visit.

Both groups treated with ZOLGENSMA were alive and free of permanent ventilation

What is permanent breathing support?

Permanent breathing support was defined as a tracheostomy or the need for continuous use of a machine to help breathe for a child who did not have a short-lasting, reversible illness or surgery.

All patients were free from breathing and feeding support

BiPap machine icon

100%

(29/29) of patients did not need temporary breathing support

Fork and spoon icon

100%

(29/29) of patients remained free of feeding support

Scale icon

97%

(28/29) of patients remained within a normal weight range (3rd-97th percentile for age)

See results from the ongoing symptomatic 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 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 the patient experiences unexpected bleeding or bruising.
  • Thrombotic microangiopathy (TMA) has been reported to occur approximately one week after ZOLGENSMA infusion. Caregivers should 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 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 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.