SPR1NT was an open-label, single-arm clinical trial of presymptomatic patients with SMA1
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 infusion. 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 SMN2.1
Study results for patients with 2 copies of SMN2 (n=14)1
Presymptomatic patients with 2 copies of SMN2 achieved age-appropriate motor milestones1
Motor milestone achievements at or before the 18-month-of-age study visit1
Primary endpoint
100% (14/14) achieved sitting without support for ≥30 seconds (Bayley)1,*
11 of those 14 patients achieved this milestone within an age-appropriate time period1,5
Exploratory endpoint
71% (10/14) achieved standing alone for ≥10 seconds (WHO)2,†
5 of those 10 patients achieved this milestone within an age-appropriate time period2,5
Exploratory endpoint
71% (10/14) achieved walking alone (WHO)2,‡
6 of those 10 patients achieved this milestone within an age-appropriate time period2,5
Age-appropriate time periods were defined according to the WHO MGRS established windows of achievements for the development of motor milestones. Based on healthy children living under conditions highly unlikely to constrain growth.5
†Independent standing ≥10 seconds assessed by WHO MGRS. WHO MGRS established window of achievement (1%–99%): 6.9–16.9 months for standing alone.2,5
‡Independent walking assessed by WHO MGRS. WHO MGRS established windows of achievement (1%–99%): 8.2–17.6 months for walking alone.2,5
ZOLGENSMA enabled continued independence from respiratory and nutritional support in presymptomatic patients with 2 copies of SMN21
Secondary endpoint
93% (13/14) maintained weight (≥3rd percentile) without the need for feeding support1,‖
No mechanical or non-oral support was used at any visit up to 18 months of age
Exploratory endpoint
100% (14/14) were free of respiratory support1,‖
At study end, patients were free of ventilation support of any kind
Study results for patients with 3 copies of SMN2 (n=15)3
Presymptomatic patients with 3 copies of SMN2 achieved age-appropriate motor milestones3
Motor milestone achievements at or before the 24-month-of-age study visit3
Primary endpoint
100% (15/15) achieved standing alone for ≥3 seconds (Bayley)3,¶
14 of those 15 patients achieved this milestone within an age-appropriate time period3,5
Secondary endpoint
93% (14/15) achieved walking alone (Bayley)3,#
11 of those 14 patients achieved this milestone within an age-appropriate time period3,5
¶Bayley-III, gross motor subtest item 40. WHO MGRS established windows of achievement (1%–99%): 6.9–16.9 months for standing alone.3,5
#Bayley-III, gross motor subtest item 43. WHO MGRS established windows of achievement (1%–99%): 8.2–17.6 months for walking alone.3,5
ZOLGENSMA enabled independence from respiratory and nutritional support in presymptomatic patients with 3 copies of SMN23
Exploratory endpoint
100% (15/15) did not require feeding support3,**
Exploratory endpoint
100% (15/15) did not require respiratory support of any kind3,**
**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 bilevel positive airway pressure (BiPAP).
LT-002 is a long-term follow-up study that includes patients from SPR1NT
LT-002 is a 15-year, ongoing, open-label, long-term follow-up of patients who completed a ZOLGENSMA clinical trial. It includes patients with SMA who were either symptomatic or presymptomatic at the time of infusion. As of June 2024, the study included 13 patients from the 2-copy cohort and 13 patients from the 3-copy cohort of the SPR1NT trial.6-8
In LT-002, patients achieved all motor milestones assessed in SPR1NT6
All 4 patients who did not achieve walking alone in the SPR1NT study achieved this milestone during LT-002 (as of June 2024).6,††, ‡‡
††Add-on was defined by treatment with any other disease-modifying therapy.6
‡‡In long-term follow-up some milestone achievements occurred after add-on therapy: crawls (2/4), pulls to stand (2/3), walks with assistance (1/2), stands alone (1/3), walks alone (1/4).6