“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
SYMPTOMATIC 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.
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.
*One patient was initially classified as presymptomatic but was later confirmed to be symptomatic and was included in the final clinical study findings.
At the 14 months of age study visit,
(20/22)* of patients were alive and did not need permanent breathing support
*One patient was initially not part of the data set but is included in the final data analysis.
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.
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.
(14/22) of patients could sit without support for at least 30 seconds at any point in the study*
Head control
(17/20) of patients had head control
Rolling
(13/22) of
patients could roll from back to sides
Standing and walking
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.
In STR1VE, the ability to thrive is a measurement of 3 components related to feeding.
(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.
(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.
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.
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).
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.
Mean CHOP INTEND scores and mean increases in CHOP INTEND scores from baseline
Improvements in CHOP INTEND scores occurred as early as 1 month after infusion
The average age at the start of the trial was 3.7 months, and patients had an average baseline CHOP INTEND score of 32.
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:
(21/22) of patients achieved a score of 40 or more
(14/22) of patients achieved a score of 50 or more
(5/22) of patients achieved a score of 60 or more
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.
*One patient was initially not part of the data set but is included in the final data analysis.
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.
Read more about survival results
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.
(14/22) of patients could sit without support for at least 30 seconds at any point in the study*
Head control
(17/20) of patients had head control
Rolling
(13/22) of
patients could roll from back to sides
Standing and walking
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.
Read more about motor milestones results
In STR1VE, the ability to thrive is a measurement of 3 components related to feeding.
(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.
Read more about ability to thrive results
(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.
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.
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).
Read more about respiratory and feeding support
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.
Mean CHOP INTEND scores and mean increases in CHOP INTEND scores from baseline
Improvements in CHOP INTEND scores occurred as early as 1 month after infusion
The average age at the start of the trial was 3.7 months, and patients had an average baseline CHOP INTEND score of 32.
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:
(21/22) of patients achieved a score of 40 or more
(14/22) of patients achieved a score of 50 or more
(5/22) of patients achieved a score of 60 or more
Read more about motor function results
The START study was the first ZOLGENSMA clinical study. The purpose was to establish safety and find the appropriate dose of ZOLGENSMA. Results from the START study are further supported by the STR1VE study results (both are measured against the natural history of SMA).
The START study enrolled 15 symptomatic patients diagnosed with SMA Type 1. Patients in the study were split into 2 groups. Three patients in group 1 received a low dose of ZOLGENSMA (about one-third of the high dose) to make sure the low dose was safe before moving to a higher dose. The 12 patients in group 2 received a higher dose.*
*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 (high dose) 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.
(12/12) of patients were alive and did not need permanent breathing support
(11/12) of patients could sit without support for at least 5 seconds
(9/12) of patients could sit without support for at least 30 seconds
(11/12) of patients achieved or maintained CHOP INTEND scores higher than 40 points
In the natural history of SMA Type 1, children who are 6 months of age or older do not score higher than 40. Most score much worse and will see their scores decrease over time.
(11/12) of patients could speak, swallow, and were receiving partial oral feeding
At the start of the study
7 patients were able to feed orally and did not require supplemental nutritional support (eg, G-tube) at the start of the study
At the end of the study
86% (6/7) of those patients still did not need nutritional support
The purpose of the START long-term follow-up (LTFU) study is to monitor the safety of ZOLGENSMA over 15 years. Ongoing results of the START LTFU study show the safety and efficacy of ZOLGENSMA up to 5 years after treatment and 5 years of age or older. All patients from the START clinical study were eligible. Three patients from group 1 and 10 patients from group 2 enrolled. The study is ongoing and the results from group 2 (high dose) are as of June 2020.
(10/10) have maintained motor milestones achieved at the end of the START study
(6/10) of patients did not need regular, daily respiratory support more than 4 years after dosing
1/6 patients required non-invasive ventilatory support (eg, BiPAP) only when sick
(2/10) patients gained an additional motor milestone of standing with assistance; neither has received additional SMA treatment
*Based on adverse event reporting death, withdrawal, or need for permanent breathing support. There were no in-person assessments between December 2019 and June 2020.
(10/10) of patients were alive and did not need permanent breathing support*
Derwin, father of Matteo
What is the most important information I should know about
ZOLGENSMA?
What is the most important information I should know about ZOLGENSMA?
What should I watch for before and after infusion with ZOLGENSMA?
What do I need to know about vaccinations and ZOLGENSMA?
Do I need to take precautions with the patient’s bodily waste?
What are the possible or likely side effects of ZOLGENSMA?
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 (children who haven’t received treatment), about 25% of children are alive without permanent breathing support at 14 months of age.