“We knew the sooner you treat, the better. Amelia was treated so early, we didn’t see any delays in anything. ZOLGENSMA has been an amazing experience that exceeded my expectations.”
Amy, mother of Amelia
Presymptomatic clinical study results
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).
SPR1NT study details
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. 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
- 3 copies of SMN2 (15 patients): 28.7 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 study results: 2 copies of the SMN2 backup gene
Patients reached age-appropriate milestones
Typically, clinical studies use standardized measurement scales to assess the progress and achievements of participants. In the SPR1NT study, the Bayley-III was used to determine children’s motor skills compared to what is expected for a “typical” developing child. The WHO-MGRS (World Health Organization Multicentre Growth Reference Study) was used to provide a timeline for motor milestone development in “unaffected” children.
(14/14) of patients with 2 copies of SMN2 could sit independently (30 seconds or more) as measured by Bayley-III
- 11/14 patients who achieved sitting independently did so within the normal development window for this milestone according to WHO-MGRS. Most unaffected children can sit without support between 4 and 9 months of age (WHO-MGRS)
(10/14) of patients stood without assistance (10 seconds or more) as measured by WHO-MGRS
- 5/10 patients achieved this milestone within an age-appropriate time
(10/14) of patients stood without assistance (10 seconds or more) as measured by WHO-MGRS
- 5/10 patients achieved this milestone within an age-appropriate time
(10/14) of patients walked without assistance (5 steps or more) as measured by WHO-MGRS
- 6/9 patients achieved this milestone within an age-appropriate time
(10/14) of patients walked without assistance (5 steps or more) as measured by WHO-MGRS
- 6/9 patients achieved this milestone within an age-appropriate time
7 of the 9 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 or Type 2.
Increased overall motor function
(14/14) of patients reached a CHOP INTEND score of 58 or higher at any visit up to 18 months of age and 93% (13/14) achieved a score of 60 points or higher
In the natural history of SMA Type 1, children who are 6 months of age or older do not score higher than 40 points. 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. It was created to measure the motor development of children with SMA Type 1.
Increased motor scores
ZOLGENSMA helped patients achieve higher scores in skills such as sitting, standing, or walking with assistance.
64%
(9/14) of patients had gross motor skills similar to same-aged children at the end of the study
100%
(14/14) of patients had fine motor skills similar to unaffected children of the same age at the end of the study
Bayley-III motor scores in patients with 2 copies of SMN2 and >1 study visit.
SPR1NT study results: 3 copies of the SMN2 backup gene
Patients reached age-appropriate milestones
(15/15) of patients stood without assistance (3 seconds or more) as measured by Bayley-III
- 14/15 patients achieved this milestone within an age-appropriate time
The median age at earliest achievement was 12½ months (range 9½-18 months). Most unaffected children can stand without support between 7 and 17 months of age (WHO-MGRS).
(15/15) of patients stood without assistance (3 seconds or more) as measured by Bayley-III
- 14/15 patients achieved this milestone within an age-appropriate time
The median age at earliest achievement was 12½ months (range 9½-18 months). Most unaffected children can stand without support between 7 and 17 months of age (WHO-MGRS).
(14/15) of patients walked without assistance (5 steps or more) as measured by Bayley-III
- 11/14 patients achieved this milestone within an age-appropriate time
The median age at earliest achievement was 14 months (range 12-19 months). Most unaffected children can walk without assistance between 8 and 18 months of age (WHO-MGRS).
(14/15) of patients walked without assistance (5 steps or more) as measured by Bayley-III
- 11/14 patients achieved this milestone within an age-appropriate time
The median age at earliest achievement was 14 months (range 12-19 months). Most unaffected children can walk without assistance between 8 and 18 months of age (WHO-MGRS).
(14/15) of patients stood with assistance (10 seconds or more) as measured by WHO-MGRS
- 11/14 patients achieved this milestone within an age-appropriate time
Most unaffected children can stand with assistance between 5 and 11 months of age (WHO-MGRS).
(14/15) of patients stood with assistance (10 seconds or more) as measured by WHO-MGRS
- 11/14 patients achieved this milestone within an age-appropriate time
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 or type 3.
Increased motor scores
In presymptomatic patients treated with ZOLGENSMA, 100% (15/15) achieved gross and fine motor scores similar to unaffected patients of the same age during at least one visit. 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.
90%
(9/10) had gross and fine motor skills similar to unaffected children of the same age at the end of the study.
Bayley-III motor scores in patients with 3 copies of SMN2 and >1 study visit.
Both groups were alive and free of permanent ventilation
(29/29) of patients were alive and free of permanent breathing support
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 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 permanent breathing support?
Permanent breathing support was defined as a 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.
100%
(29/29) of patients did not need temporary breathing support
100%
(29/29) of patients remained free of feeding support
93%
(13/14) of patients in the 2-copy group remained within a normal weight range (≥3rd percentile for age and gender)
Amelia, treated at 11 days old and pictured at 3½ years, was diagnosed with SMA.
See results from the symptomatic SMA studies
See resultsSee the safety data of ZOLGENSMA in clinical studies
See ZOLGENSMA safetyImportant 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?
What are the possible or likely side effects of ZOLGENSMA?
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.
In the natural history of SMA Type 1, patients are not able to sit.