SPR1NT: An open-label, single-arm clinical trial of presymptomatic patients with SMA1

SPR1NT is a clinical trial of patients with SMA who have 2 or 3 copies of SMN2 (N=30)1,a

All patients enrolled in the study were less than 6 weeks of age and did not display any symptoms of SMA at the time of infusion1

aOne enrolled patient had 4 copies of SMN2 and is not included in the efficacy analysis. This patient will be included in the safety population only.

The SPR1NT trial was divided into 2 cohorts based on SMN2 copy number—patients with 2 copies of SMN2 and those with 3 copies of SMN2

Completed study results for patients with 2 copies of SMN2 (n=14)

All patients with 2 copies of SMN2 reached 18-months-of-age (study end) and met the secondary endpoint of survival.2,a

aEvent-free survival was defined as avoidance of both death and permanent ventilation (tracheostomy or ≥16 hours respiratory assistance per day continuously for ≥14 days in the absence of an acute reversible illness, excluding perioperative ventilation) at 14 months of age.

Presymptomatic patients with 2 copies of SMN2 achieved age-appropriate motor milestones, after ZOLGENSMA2

100% (14/14) of patients achieved the primary endpoint of sitting without support for ≥30 seconds up to the 18-months-of-age visit2,a
  • 79% (11/14) of patients achieved this milestone within an age-appropriate time period2
  • Age-appropriate time periods are based on the WHO MGRS of healthy children living under conditions highly unlikely to constrain growth3

Age-appropriate time periods were defined according to the WHO Multicenter Growth Reference Study (MGRS) established windows of achievements for the development of motor milestones.

aBayley-III, gross motor subtest item 26. WHO MGRS established windows of achievement (1%-99%): 3.8-9.2 months for sitting without support.2,3

bIndependent standing ≥10 seconds assessed by WHO MGRS. WHO MGRS established window of achievement (1%-99%): 6.9-16.9 months for standing alone.2,3

cIndependent walking assessed by WHO MGRS. WHO MGRS established windows of achievement (1%-99%): 8.2-17.6 months for walking alone.2,3

Icon: 100% of patients with 2 copies of SMN2 in the SPR1NT clinical trial achieved
sitting without support for ≥30 seconds

Primary endpoint:

Achieved sitting without support for ≥30 seconds (Bayley)2,a

11 of 14 patients achieved sitting without support within an age-appropriate time period

Icon: 71% of patients with 2 copies of SMN2 achieved standing alone for ≥10
seconds

Exploratory endpoint:

Achieved standing alone for ≥10 seconds (WHO)2,b

5 of 10 patients achieved this milestone within an age-appropriate time period

Exploratory endpoint:

Achieved walking alone (WHO)2,c

6 of 10 patients achieved this milestone within an age-appropriate time period

Age-appropriate time periods were defined according to the WHO Multicenter Growth Reference Study (MGRS) established windows of achievements for the development of motor milestones.

Based on participants without health, environmental, or economic constraints on growth.

aBayley-III, gross motor subtest item 26. WHO MGRS established windows of achievement (1%-99%): 3.8-9.2 months for sitting without support.2,3

bIndependent standing ≥10 seconds assessed by WHO MGRS. WHO MGRS established window of achievement (1%-99%): 6.9-16.9 months for standing alone.2,3

cIndependent walking assessed by WHO MGRS. WHO MGRS established windows of achievement (1%-99%): 8.2-17.6 months for walking alone.2,3

ZOLGENSMA enabled continued independence from nutritional support in presymptomatic patients with 2 copies of SMN2 2

aAll patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline.2

Nutritional statusa:

Weight maintenance

(≥3rd percentile for age and gender as defined by WHO)

93% (13/14) of patients

were able to maintain weight without need for non-oral or mechanical feeding support at all visits up to 18 months of age

All patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline.2

ZOLGENSMA enabled continued independence from respiratory support in all patients treated presymptomatically2

In natural history, most patients with SMA Type 1 required respiratory support by 12 months of age4

aZOLGENSMA-treated patients in SPR1NT were separated into 2 cohorts by SMN2 copy number. 14 patients had 2 copies of SMN2. 15 patients had 3 copies of SMN2. All patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline. Ventilatory support included noninvasive ventilatory support, invasive ventilatory support, cough assist, or BiPAP. 

Respiratory statusa:

Respiratory status

100% (14/14) of patients

were free of ventilation support of any kind at study end

aZOLGENSMA-treated patients in SPR1NT were separated into 2 cohorts by SMN2 copy number. 14 patients had 2 copies of SMN2. 15 patients had 3 copies of SMN2. All patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline. Ventilatory support included noninvasive ventilatory support, invasive ventilatory support, cough assist, or BiPAP. 

ZOLGENSMA enabled age-appropriate development of gross motor function5

64% (9/14) of patients with 2 copies of SMN2 assessed at study end had gross motor performance similar to same-age children5,a,b

SD=standard deviation.

aGross motor function was measured by the Bayley Scales of Infant and Toddler Development, a well-accepted, standardized tool to assess the development of children between the ages of 1 and 42 months and compared to a standardized norm.6

bEach line represents the raw scores of an individual patient on the Bayley-III gross motor subtest. The normal range for raw scores is based on scaled score equivalents for unaffected patients: mean ± 2 standard deviations (4-16 score [mean = 10, SD = 3, Range of 1-19]).5,6

SD=standard deviation.

aGross motor function was measured by the Bayley Scales of Infant and Toddler Development, a well-accepted, standardized tool to assess the development of children between the ages of 1 and 42 months and compared to a standardized norm.6

bEach line represents the raw scores of an individual patient on the Bayley-III gross motor subtest. The normal range for raw scores is based on scaled score equivalents for unaffected patients: mean ± 2 standard deviations (4-16 score [mean = 10, SD = 3, Range of 1-19]).5,6

Presymptomatic patients with 2 copies of SMN2 achieved increased motor function scores from baseline

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.7

Increases from baseline in CHOP INTEND were seen as early as 1 month post infusion in patients with 2 copies of SMN2 2

100% (14/14) of patients in the 2-copy cohort achieved a CHOP INTEND score ≥58 points at any visit up to 18 months of age2,a

  • 93% (13/14) of patients achieved a CHOP INTEND score ≥60b

aScores on the CHOP INTEND scale of motor function range from 0 to 64, with higher scores indicating better function.7

bThe patient who did not achieve 60 had achieved 58 or higher 3 times by day 27 post dosing and per protocol did not undergo additional testing.2

cThe dark gray line at 40 represents the highest possible CHOP INTEND score that children with the most severe form of SMA would achieve or maintain, according to natural history.8

SD=standard deviation

aScores on the CHOP INTEND scale of motor function range from 0 to 64, with higher scores indicating better function.7

bOf the 2 remaining patients, 1 patient achieved a maximum post-baseline score of 55 points, and 1 patient achieved 3 consecutive scores ≥58 and, per protocol, did not undergo additional CHOP INTEND examinations.2

cThe dark gray line at 40 represents the highest possible CHOP INTEND score that children with the most severe form of SMA would achieve or maintain, according to natural history.8

Completed study results for patients with 3 copies of SMN2 (n=15)

All patients with 3 copies of SMN2 reached 24-months-of-age (study end) and were free of permanent ventilation.5,a

aPermanent ventilation (tracheostomy or ≥16 hours respiratory assistance per day continuously for ≥14 days in the absence of an acute reversible illness, excluding perioperative ventilation).5  

Presymptomatic patients with 3 copies of SMN2 achieved age-appropriate motor milestones, after ZOLGENSMA5

100% (15/15) of patients achieved the primary endpoint of standing without support up to the 24-months-of-age visit5,a
  • 93% (14/15) of patients achieved this milestone within an age-appropriate time period5
  • Age-appropriate time periods are based on the WHO MGRS of healthy children living under conditions highly unlikely to constrain growth3

Age-appropriate time periods were defined according to the WHO Multicenter Growth Reference Study (MGRS) established windows of achievements for the development of motor milestones.

Based on healthy children living under conditions highly unlikely to constrain growth. 3

aBayley-III, gross motor subtest item 40. WHO MGRS established windows of achievement (1%-99%): 6.9-16.9 months for standing alone.3,5

bBayley-III, gross motor subtest item 43. WHO MGRS established windows of achievement (1%-99%): 8.2-17.6 months for walking alone.3,5

cStands with assistance as assessed by WHO MGRS. WHO MGRS established windows of achievement (1%-99%): 4.8-11.4 months for standing with assistance.3

Icon: 100% of patients with 3 copies of SMN2 in the SPR1NT trial achieved the
primary endpoint of standing alone

Primary endpoint:

Achieved standing alone for ≥3 seconds (Bayley)5,a

14 of 15 patients achieved this milestone within an age-appropriate time period

Icon: 93% of patients with 3 copies of SMN2 in the SPR1NT trial achieved the
secondary endpoint of walking alone

Secondary endpoint:

Achieved walking alone (Bayley)5,b

11 of 14 patients achieved this milestone within an age-appropriate time period

Icon: 93% of patients with 3 copies of SMN2 in the SPR1NT trial achieved walking
with assistance

Exploratory endpoint:

Achieved standing with assistance (WHO)5,c

11 of 14 patients achieved this milestone within an age-appropriate time period

Age-appropriate time periods were defined according to the WHO Multicenter Growth Reference Study (MGRS) established windows of achievements for the development of motor milestones.

Based on healthy children living under conditions highly unlikely to constrain growth. 3

aBayley-III, gross motor subtest item 40. WHO MGRS established windows of achievement (1%-99%): 6.9-16.9 months for standing alone.3,5

bBayley-III, gross motor subtest item 43. WHO MGRS established windows of achievement (1%-99%): 8.2-17.6 months for walking alone.3,5

cStands with assistance as assessed by WHO MGRS. WHO MGRS established windows of achievement (1%-99%): 4.8-11.4 months for standing with assistance.3

ZOLGENSMA enabled continued independence from nutritional support in presymptomatic patients with 3 copies of SMN2

aAll patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline.1

Nutritional status5,a:

Feeding support status

100% (15/15) of patients

did not require feeding support

ZOLGENSMA enabled continued independence from respiratory support in all patients treated presymptomatically5

In natural history, most patients with SMA Type 1 required respiratory support by 12 months of age4

aAll patients were required to be able to swallow thin liquids and be free from ventilatory support at baseline. Ventilatory support included noninvasive ventilatory support, invasive ventilatory support, cough assist, or BiPAP.1

Respiratory statusa:

Respiratory status

100% (15/15) of patients

did not require respiratory support of any kind

ZOLGENSMA enabled age-appropriate development of gross motor function in patients with 3 copies of SMN2

100% (10/10) of patients assessed had gross motor performance similar to same-aged children at 24 months of age5,a,b

aGross motor function was measured by the Bayley Scales of Infant and Toddler Development, a well-accepted, standardized tool to assess the development of children between the ages of 1 and 42 months, and compared to a standardized norm. The normal range for scores on the gross motor subtest is based on scaled score equivalents for unaffected patients: mean ±2 standard deviations (4-16 score [mean=10, SD=3, range of 1-19]).5,6

bEach line represents the raw scores of an individual patient on the Bayley-III gross motor subtest.

aGross motor function was measured by the Bayley Scales of Infant and Toddler Development, a well-accepted, standardized tool to assess the development of children between the ages of 1 and 42 months, and compared to a standardized norm. The normal range for scores on the gross motor subtest is based on scaled score equivalents for unaffected patients: mean ±2 standard deviations (4-16 score [mean=10, SD=3, range of 1-19]).5,6

bEach line represents the raw scores of an individual patient on the Bayley-III gross motor subtest.

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