Children treated after
showing SMA symptoms (symptomatic)
Treated at ~2½ months old
ZOLGENSMA® (onasemnogene abeparvovec-xioi) was studied in children who were showing symptoms (symptomatic) of spinal muscular atrophy (SMA) before treatment. The key trial looked at safety and efficacy and was called STR1VE. ZOLGENSMA was also studied in symptomatic children in a trial called START, which studied safety and dosing.
STR1VE study
The main purpose of the STR1VE study was to establish the efficacy and safety of ZOLGENSMA. Efficacy was measured by the ability to sit independently for 30 seconds or more at 18 months of age and event-free survival at 14 months of age. Results were measured against the natural course of SMA without treatment. The study enrolled 22* symptomatic children 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 intravenous (IV) infusion. The average age at dosing was 3.7 months (range 0.5-5.9 months). Children received the therapeutic dose of ZOLGENSMA (dose currently approved by the FDA). Children were followed through their 18 months of age study visit.
*One child was initially classified as presymptomatic but was later confirmed to be symptomatic and was included in the final clinical study findings.
Substantially increased event-free survival
91%
(20/22) of children† were free of ventilation support at the 14 months of age study visit
†One child was initially not part of the data set but is included in the final data analysis.
Typically, about 25% of children with SMA Type 1 who have not received treatment are alive without permanent breathing support at 14 months of age.
One child passed away at 7.8 months of age from causes deemed unrelated to treatment.
One child was withdrawn from the study at 11.9 months of age and required permanent ventilation at 11 months of age prior to leaving the study.
"Substantially increased" established through comparison between the ZOLGENSMA treated group and The Pediatric Neuromuscular Clinical Research (PNCR) Network study control population of untreated infants with SMA Type 1.
Event-free survival
Substantially increased event-free survival
91%
(20/22) of children† were free of ventilation support at the 14 months of age study visit
†One child was initially not part of the data set but is included in the final data analysis.
Typically, about 25% of children with SMA Type 1 who have not received treatment are alive without permanent breathing support at 14 months of age.
One child passed away at 7.8 months of age from causes deemed unrelated to treatment.
One child was withdrawn from the study at 11.9 months of age and required permanent ventilation at 11 months of age prior to leaving the study.
"Substantially increased" established through comparison between the ZOLGENSMA treated group and The Pediatric Neuromuscular Clinical Research (PNCR) Network study control population of untreated infants with SMA Type 1.
Motor milestones
New motor milestones were achieved with ZOLGENSMA
59%
(13/22) of children could sit without support for at least 30 seconds
64% (14/22 children) of children could sit without support for at least 30 seconds at any point in the study†
Children with SMA Type 1 who do not receive treatment are never able to sit independently.
†One child 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).
85%
(17/20) of children had head control
59%
(13/22) of children could roll from back to sides
1 child
could stand and walk independently. This child was treated at 1.1 months of age and could stand at 14.7 months and walk at 15.3 months
Ability to thrive
Helped children maintain the ability to thrive
In STR1VE, the ability to thrive is a measurement of 3 components related to feeding.
41%
(9/22) of children met all 3 components of ability to thrive at 18 months of age
For children with SMA Type 1 who do not receive any treatment, nearly all require feeding support at 12 months of age
55%
(12/22) of children had the ability to swallow thin liquids measured by a swallowing test
86%
(19/22) of children were free from non-oral feeding support (G-tube)
64%
(14/22) of children had the ability to maintain weight that’s consistent with age†
†≥3rd percentile for age and gender.
Respiratory & nutrition
Helped children stay free of
breathing and feeding support
68%
(15/22) of children did not need breathing support† during the study
†If a child needs breathing support, it means he or she receives help breathing through the use of ventilator equipment, such as something called a bilevel positive airway pressure (BiPAP) machine.
68%
(15/22) of children did not need feeding support‡ during the study§
‡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).
For children with SMA Type 1 who did not receive any treatment, the majority required respiratory and feeding support.
§Four children had temporary feeding support once during the study (lasting 6 to 91 days); 3 children 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.
Motor function
Helped children improve and maintain motor function
Children 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 were measured. 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 children had an average baseline CHOP INTEND score of 32.
Children 6 months of age or older with SMA Type 1 who do not receive any treatment almost never achieve scores higher than 40.
95%
(21/22) of children achieved
a score of 40 or more
64%
(14/22) of children achieved
a score of 50 or more
23%
(5/22) of children achieved
a score of 60 or more
The START study enrolled 15 children diagnosed with SMA Type 1 who had symptoms: all children were younger than 8 months old. Children in the study were split into 2 groups. Three children 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 children in group 2 received a higher dose* (approximately the therapeutic dose); the results below are for this group of children. All results were measured against the natural course of SMA without treatment.
The results below are for START group 2: these children received a higher dose* (approximately the therapeutic dose) of ZOLGENSMA.
*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 children in this study is an estimate. Children 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.
Survival/Breathe Without Support
100%
(12/12) of children were alive and did not need breathing support
Sit Without Support
Motor milestones reached and maintained
92%
(11/12) of children could sit without support for at least 5 seconds
75%
(9/12) of children could sit without support for at least 30 seconds
Motor Function
92%
(11/12) of children achieved or maintained CHOP INTEND scores higher than 40 points
Children 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.
Nutrition, Feeding & Speaking
92%
(11/12) of children could speak, swallow, and were receiving partial oral feeding
Nearly all children who did not require nutritional support at the start of the study did not need it at the end of the study. 7 children 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 children still did not need nutritional support.
ZOLGENSMA substantially increased event-free survival in patients from the high-dose group
"Substantially increased" established through comparison between the ZOLGENSMA treated group and The Pediatric Neuromuscular Clinical Research (PNCR) Network study control population of untreated infants with SMA Type 1.
The purpose of the START LTFU study is to monitor the safety of ZOLGENSMA over 15 years.
All children from the START clinical study were eligible. Three children from the low-dose group and 10 children from the high-dose group enrolled. As of May 2022, data have been collected for up to 8 years after treatment; children monitored were between 6.6 and 8.5 years old.
The results below are from the high-dose group as of May 2022. These children were followed for up to 7.5 years; children were between 6.6 and 7.9 years old.
Study results: high-dose group as of May 2022
100%
(10/10) of children have maintained motor milestones achieved at the end of the START study
70%
(7/10) of children did not need regular, daily breathing support at an average of more than 7 years after dosing
3/10 children had non-invasive ventilatory support (BiPAP and cough assist)
30%
(3/10) of children gained an additional motor milestone of standing with assistance
2 of these milestones were achieved without additional SMA therapy
After over 7 years, every child was alive and did not need permanent breathing support
100%
(10/10) of children were alive and did not need permanent breathing support*
*Permanent ventilation means the need for a machine to help with breathing (invasive ventilation) or at least 16 hours a day of noninvasive ventilation support for 2 weeks or more.
