STR1VE: An open-label, single-arm clinical trial that demonstrated the efficacy of ZOLGENSMA®(onasemnogene abeparvovec-xioi)1

STR1VE is a completed, Phase 3 trial of symptomatic patients with SMA Type 1 (N=22)1,a

Patients were symptomatic and less than 6 months of age at the time of infusion and studied until 18 months of age.

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at baseline and included in the final ITT analysis.2

ZOLGENSMA significantly increased event-free survival in patients with SMA Type 1 compared with natural history2

91% (20/22) of patients were alive and free of permanent ventilation at the 14-months-of-age study visit, a primary endpoint2,a-c

  • Results were maintained through 18 months of age2,d

aEvent is defined as death or the need for permanent ventilatory support consisting of ≥16 hours of respiratory assistance per day continuously for ≥14 days.2

bOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

cOne patient died at 7.8 months from respiratory failure, which was deemed unrelated to treatment. One patient withdrew consent at 11.9 months of age; this patient was determined by the investigator to have required permanent ventilation at the time of discontinuation.2

dOne patient discontinued participation at the age of 18.0 months, before the month 18 end-of-study-visit, due to an adverse event of respiratory distress (considered unrelated to study drug). The patient was alive without permanent ventilation at the time of withdrawal.2

eNatural history: The Pediatric Neuromuscular Clinical Research (PNCR) Network study population, with bi-allelic deletion of SMN1 gene, 2 copies of SMN2, and onset of SMA symptoms at age ≤6 months, was used as a matched control cohort for START and STR1VE studies.3

aEvent is defined as death or the need for permanent ventilatory support consisting of ≥16 hours of respiratory assistance per day continuously for ≥14 days.2

bOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

cOne patient died at 7.8 months from respiratory failure, which was deemed unrelated to treatment. One patient withdrew consent at 11.9 months of age; this patient was determined by the investigator to have required permanent ventilation at the time of discontinuation.2

dOne patient discontinued participation at the age of 18.0 months, before the month 18 end-of-study-visit, due to an adverse event of respiratory distress (considered unrelated to study drug). The patient was alive without permanent ventilation at the time of withdrawal.2

eNatural history: The Pediatric Neuromuscular Clinical Research (PNCR) Network study population, with bi-allelic deletion of SMN1 gene, 2 copies of SMN2, and onset of SMA symptoms at age ≤6 months, was used as a matched control cohort for START and STR1VE studies.3

New motor milestones were achieved with ZOLGENSMA2

59% (13/22) of patients achieved sitting without support for ≥30 seconds at the 18-months-of-age study visit, a primary endpoint2

One additional patient achieved the milestone of sitting without support for ≥30 seconds at 16 months of age; however, this milestone was not reconfirmed at the 18-months-of-age visit.2

aOne patient was initially classified as presymptomatic and removed from the ITT data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bBayley-III, gross motor subtest item 4. Two patients demonstrated the milestone of head control at screening visit prior to ZOLGENSMA dosing; therefore n=20 was used for this calculation.2

cBayley-III, gross motor subtest item 20.2

dBayley-III, gross motor subtest item 26.2

eBayley-III, gross motor subtest item 33 (supports own weight ≥2 seconds).2

fThese milestones were achieved by the same patient.2

gBayley-III, gross motor item 40.2

hBayley-III, gross motor item 37.2

iBayley-III, gross motor item 43.2

aOne patient was initially classified as presymptomatic and removed from the ITT data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bBayley-III, gross motor subtest item 4. Two patients demonstrated the milestone of head control at screening visit prior to ZOLGENSMA dosing; therefore n=20 was used for this calculation.2

cBayley-III, gross motor subtest item 20.2

dBayley-III, gross motor subtest item 26.2

eBayley-III, gross motor subtest item 33 (supports own weight ≥2 seconds).2

fThese milestones were achieved by the same patient.2

gBayley-III, gross motor item 40.2

hBayley-III, gross motor item 37.2

iBayley-III, gross motor item 43.2

64% (14/22)of patients achieved sitting without support for ≥30 seconds, at any point during the STR1VE trial2,a,b

vs

In natural history, patients with SMA Type 1 are not able to sit unassisted4

aBayley-III, gross motor subtest item 26.2

bOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been later confirmed to be symptomatic at baseline and included in the final ITT analysis.2

ZOLGENSMA helped patients with SMA Type 1 maintain the ability to thrive2

41% (9/22) of patients met all 3 criteria for ability to thrive at 18 months of age, a secondary endpoint2,a,b

In natural history, most patients with SMA Type 1 older than 12 months of age required feeding support.3

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.

bAbility to thrive, a secondary endpoint, is defined as ability to tolerate thin liquids as demonstrated through a formal swallowing test, maintenance of weight (≥3rd percentile for age and gender as defined by WHO guidelines), and independence from mechanical or non-oral nutritional support.

Ability to thrive at 18 months of age was a composite endpoint consisting of2,a:

Swallowing thin liquids

55% (12/22) of patients

could swallow and tolerate thin liquidsa

Non-oral feeding support

86% (19/22) of patients

were free of ongoing non-oral feeding supporta

Maintenance of weight

64% (14/22) of patients

maintained weight consistent with age, at or above the 3rd percentilea

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and is included in the final ITT analysis.

bAbility to thrive, a secondary endpoint, is defined as ability to tolerate thin liquids as demonstrated through a formal swallowing test, maintenance of weight (≥3rd percentile for age and gender as defined by WHO guidelines), and independence from mechanical or non-oral nutritional support.

ZOLGENSMA helped maintain respiratory status compared with natural history2,3

4/22 patients required ventilatory support as assessed by Trilogy BiPAP data alone at 18 months of age, a secondary endpoint2,a

In natural history, most patients with SMA Type 1 required respiratory support by 12 months of age.3

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bFive patients had documented Trilogy BiPAP use, and two patients had other noninvasive ventilatory support.2

Noninvasive ventilatory support

68% (15/22) of patients

did not require noninvasive ventilatory support at any point during the study2,a,b

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat(ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and is included in the final ITT analysis.2

bFive patients had documented Trilogy BiPAP use, and two patients had other noninvasive ventilatory support.2

ZOLGENSMA resulted in maintained motor function improvements from baseline2

Motor function was assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)

CHOP INTEND was specifically developed to assess motor function in patients with SMA. The CHOP INTEND score is measured in points, which are assigned based on a patient’s ability to perform specific motor skills. The test consists of 16 measures, each scored on a scale of 0-4, with the highest possible score being 64 points.5

Patients achieved CHOP INTEND scores not seen in natural history.2,6

Patients with SMA Type 1 in historical controls did not typically achieve and maintain CHOP INTEND scores of ≥40.6

At the end of STR1VE, nearly all patients (95%; 21/22) achieved or maintained a CHOP INTEND score of ≥402,a,b

SD=standard deviation 

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bScores on the CHOP INTEND scale of motor function range from 0 to 64, with higher scores indicating better function.5

cThe dark gray line at 40 representes the highest CHOP INTEND score that children with the most severe form of SMA would achieve or maintain, according to natural history.6

dIndividual patient data are shown within the CHOP INTEND chart. Per protocol, patients who achieved 3 consecutive CHOP INTEND scores ≥58 did not undergo any additional CHOP INTEND examinations.

SD=standard deviation 

aOne patient was initially classified as presymptomatic and removed from the intent-to-treat (ITT) data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bScores on the CHOP INTEND scale of motor function range from 0 to 64, with higher scores indicating better function.5

cThe dark gray line at 40 representes the highest CHOP INTEND score that children with the most severe form of SMA would achieve or maintain, according to natural history.6

dIndividual patient data are shown within the CHOP INTEND chart. Per protocol, patients who achieved 3 consecutive CHOP INTEND scores ≥58 did not undergo any additional CHOP INTEND examinations.

Rapid improvements in CHOP INTEND from baseline were seen as early as 1 month post infusion

One month after treatment, patients’ scores improved by a mean change of 6.9 points (N=22) from baseline. Improvements continued at 12 months, with a mean change 16.4 points (n=16) from baseline.2,a

aOne patient was initially classified as presymptomatic and removed from the ITT data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bBaseline for natural history was measured at 6 months of age (Kolb et al). Additional CHOP INTEND assessments were performed at 9, 12 and 18 months of age (3, 6 and 12 months from baseline). Baseline scores for ZOLGENSMA patients were performed prior to infusion and patients were assessed every month following infusion, through the duration of the study.7

cBaseline scores for ZOLGENSMA patients were performed prior to infusion and patients were assessed every month following infusion, through the duration of the study. Per protocol, patients who achieved 3 consecutive CHOP INTEND scores ≥58 did not undergo any additional CHOP INTEND examinations.

aOne patient was initially classified as presymptomatic and removed from the ITT data set included in the Prescribing Information. The patient has been confirmed to be symptomatic at the time of gene therapy and included in the final ITT analysis.2

bBaseline for natural history was measured at 6 months of age (Kolb et al). Additional CHOP INTEND assessments were performed at 9, 12 and 18 months of age (3, 6 and 12 months from baseline). Baseline scores for ZOLGENSMA patients were performed prior to infusion and patients were assessed every month following infusion, through the duration of the study.7

cBaseline scores for ZOLGENSMA patients were performed prior to infusion and patients were assessed every month following infusion, through the duration of the study. Per protocol, patients who achieved 3 consecutive CHOP INTEND scores ≥58 did not undergo any additional CHOP INTEND examinations.

START Trial

An open-label, single-arm, Phase 1, dose-escalation clinical trial supporting the efficacy of ZOLGENSMA