91% (20/22) of patients were alive and free of permanent ventilation at the 14-months-of-age study visit, a primary endpoint.^1,†,‡,§

• Results were maintained through 18 months of age^||

^†Survival was defined as absence of death or permanent ventilation (tracheostomy or ≥16 hours daily noninvasive ventilation support for ≥14 days in the absence of acute reversible illness or perioperative ventilation).^1
‡One 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 replacement therapy and included in the final ITT analysis.^3
§One 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 noninvasive ventilation at the time of discontinuation.^1
||One 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.¹

59% (13/22) of patients achieved sitting without support for ≥30 seconds at the 18-month-of-age study visit, a primary endpoint^1,2

^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 replacement therapy and included in the final ITT analysis.^3
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.^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 42.²

.

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

One month post infusion, patients' CHOP INTEND scores improved by a mean change of 6.9 points from baseline (N=22). Improvements continued at 6 months, with a mean change of 14.6 points from baseline (n=20).^1,**

**One 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 replacement therapy and included in the final ITT analysis.³

ZOLGENSMA demonstrated durability of effect up to 9.6 years after treatment⁷

START was an open-label, single-arm, dose-escalation clinical trial that enrolled 15 patients with SMA type 1. Patients were symptomatic with onset of clinical symptoms before 6 months of age. Trial participants were divided into 2 cohorts—a low-dose cohort (n=3) and a high-dose cohort (n=12).^5,9,††

Patients from START continued into an ongoing, long-term follow-up study. The long-term follow-up study of START began after the completion of the 24-month START trial and is planned to last 15 years. A total of 13 patients, 10 from the high-dose cohort and 3 from the low-dose cohort, are enrolled in the study.⁶

^††The dosage received by patients in the low-dose cohort was approximately one-third of the dosage received by patients in the high-dose cohort. However, the precise dosages of ZOLGENSMA received by patients in this completed clinical trial are unclear due to a change in the method of measuring ZOLGENSMA concentration, and to decreases in the concentration of stored ZOLGENSMA over time.⁹

Patients in START achieved key survival milestones that were maintained in the long-term follow-up (LTFU)

As of July 2024, in the high-dose cohort, the mean time since treatment was 8.3 years (range 6.8–9.6), and the mean age at last follow-up was 8.5 years (range 6.9–10.0).^{7, 8}

By the end of START, motor milestones were achieved and maintained with ZOLGENSMA in patients from the high-dose cohort⁵

75% (9/12) of patients could sit without support for ≥30 seconds by the end of the 24-month study. In natural history, 0% of patients with SMA type 1 were able to sit unassisted.^5,10

^aBayley-III, gross motor subtest item 20.
^bBayley-III, gross motor subtest item 22.
^cBayley-III, gross motor subtest item 26.
^dAlso includes patients who are observed sitting alone for ≥5, ≥10, or ≥30 seconds. Patients sitting without support ≥30 seconds are included in the total of ≥5 seconds.