The permanent J-code for ITVISMA^® is J3405, and goes into effect starting on July 1, 2026 for all sites of care.

Explore the clinical data. Scarlette lives with SMA and hasn't received ITVISMA. She was compensated for her time.

With one dose of ITVISMA, patients with SMA achieved significant motor function gains at the end of Study Follow-Up Period 1^1,*

STEER study design

STEER was a randomized, double-blind, sham-controlled, multicenter, registrational, phase 3 study assessing efficacy in 126 patients with spinal muscular atrophy (SMA), aged 2 to <18 years, who were treatment naive and able to sit independently^† but never had the ability to walk independently.^1,2,‡

The total duration of the study was 64 weeks, including 2 treatment periods²:

Treatment Period 1: ITVISMA or sham administration on Day 1 followed by a 52-week follow-up period for assessments in efficacy and safety
Treatment Period 2: At Week 52+1, all eligible patients who initially received the sham procedure on Day 1 received ITVISMA and those who had initially received ITVISMA received the sham procedure

*End of Follow-Up Period 1 was defined as the average of the Week-48 and Week-52 assessments.²
^†Independent sitting is defined as sitting up straight with the head erect for at least 10 seconds without using arms or hands to balance the body or support the position.²
^‡Independent walking is defined as the ability to balance the body and control forward-stepping movements without assistance.²

STEER endpoints

STEER enrollment criteria

Baseline demographics and characteristics

Baseline demographics and characteristics²
	ITVISMA (n=75)	Sham (n=51)	Overall (N=126)
Age at dosing, years
Mean (SD)	5.89 (3.58)	5.87 (3.05)	5.88 (3.36)
Range	2.1–16.6	2.4–14.2	2.1–16.6
Mean (range) age at SMA symptom onset, months	12.7 (6–31)	12.6 (6–33)	12.7 (6–33)
Sex, n (%)
Male	34 (45.3)	28 (54.9)	62 (49.2)
Female	41 (54.7)	23 (45.1)	64 (50.8)
SMN2 copy number, n (%)
2	1 (1.3)	4 (7.8)	5 (4.0)
3	73 (97.3)	46 (90.2)	119 (94.4)
≥4	1 (1.3)	1 (2.0)	2 (1.6)
HFMSE score^a
Mean (SD)	17.97 (10.11)	18.17 (9.76)
Range	1.0–41.0	2.0–42.5
RULM score^b
Mean (SD)	16.52 (6.74)	17.42 (6.35)
Range	4.0–31.7	4.3–31.0

^aScores range from 0 to 66, with higher scores indicating better motor function.²
^bScores range from 0 to 37, with higher scores indicating better function.²

End of Follow-Up Period 1 (52 week) data

HFMSE score

Primary endpoint was met:

Clinically meaningful and statistically significant improvement was seen in HFMSE total score with ITVISMA compared to sham-control group at end of Follow-Up Period 1 in the STEER study^1,2,*,†

Change from baseline to end of Follow-Up Period 1 in HFMSE total score for the overall study (FAS)^1,2,§

The change from baseline in HFMSE score with ITVISMA compared to Sham as indicated by the STEER study in the end of Follow-Up Period 1. The result was a 1.88 point LS mean difference between the two.

*Per the Prescribing Information, the primary endpoint was assessed using a mixed model repeated measures (MMRM) model with the Full Analysis Set (FAS) population, which included all participants who were dosed with ITVISMA (n=75) or who underwent sham procedure (n=51). Please note that the STEER publication reports the ITVISMA cohort as n=74 and the sham group as n=50. These numbers represent patients with an assessment at the end of Follow-up Period 1.^1,2

The efficacy endpoint variable was analyzed using a linear mixed model repeated measures (MMRM) method with the observed change from baseline in HFMSE total score at all post-baseline visits as the dependent variable. The fixed effects included treatment, visit, treatment by visit interaction, the strata, and the baseline HFMSE total score as covariate. An unstructured covariance matrix was used.^2,‡

Patients who received ITVISMA (n=75) achieved a statistically significant and clinically meaningful improvement of 2.39 points in Hammersmith Functional Motor Scale — Expanded (HFMSE) score vs a 0.51-point improvement for the sham-control group (n=51) at end of Follow-Up Period 1, with an LS mean difference of 1.88 points (95% CI: 0.51, 3.25; P=.0074).^1,§

^†End of Follow-Up Period 1 was defined as the average of the Week-48 and Week-52 assessments.²
^‡Assessed using the Full Analysis Set (FAS) population, which included all participants who were dosed with ITVISMA (n=75) or who underwent sham procedure (n=51).^1,2
^§Least squares (LS) mean is standard errors of the mean (SEM).²

The STEER study primary endpoint data can be understood better in the context of the HFMSE scale

HFMSE consists of 33 items, each scored on a scale of 0 to 2, for a score range of 0 to 66. Higher scores indicate better motor function.¹

HFMSE has been confirmed for its validity and reliability as an SMA-specific assessment in numerous studies.³

HFMSE scale

HFMSE scale⁴ Each item is measured on a 3-point scale from 0 to 2 2 indicates that the activity can be performed without modifications 1 means that the activity can be performed with modifications or adaptations 0 signifies that the activity cannot be performed
Item	Activity clusters	Activities
1	Sitting	Able to sit on plinth/chair^a
2		Able to sit on plinth/floor with legs straight out^a
3		Able to bring one hand to head above ear level^b
4		Able to bring both hands to head above ear level^b
5	Rolling	Roll from supine to sides^c
6-7		Roll from prone to supine^c
8-9		Roll from supine to prone^c
10	Transition/ crawling	Able to lie down from sitting^d
11		Able to prop on forearms with head raised^e
12		Able to lift head from prone^e,f
13		Able to prop on extended arms^g
14		Able to sit up from lying^d
15		Able to 4-point kneel^e,g
16		Able to crawl on all 4 points
17		Lift head from supine^e,h
18	Standing/ stepping	Stand with support of hand/trunk^e
19		Stand without support^e
20		Able to walkⁱ
21-22	Transitions/ kneeling	Able to flex hip from supine^j
23-24		Able to half-kneel from high kneel^k
25-26		Able to stand from high kneel^l
27		Able to go from standing to sitting^m
28	Squatting/ jumping	Able to squatⁿ
29	Squatting/ jumping	Able to jump^o
30-31	Stairs	Go up and down stairs with railing support^p
32-33	Stairs	Go up and down stairs without railing support^q
HIGHEST SCORE: 66 POINTS

^aWith or without hand support. ^bWith head/trunk stable or with head flex. ^cIn one or both directions, with or without arm support. ^dBy side-lying or with body support. ^eFor at least 3 seconds. ^fWith arms at side or in mid position. ^gWith or without head up. ^hHead lifted in mid-line or with partial/no neck flex. ⁱFor at least 2 to 4 steps. ^jOn either side with full flex or through partial range. ^kOn either side, with or without arm support. ^lLeading with either leg through half-kneel, with or without arm support. ^mWith or without arm support/crashes. ⁿWith or without arm support, and with full flex >90 degrees or partial range of motion. ^oAt least 2 to 12 inches, both feet simultaneously. ^pAt least 2 to 4 stairs, with alternating feet or step-to pattern, and with one or both rails. ^qAt least 2 to 4 stairs, with alternating feet or step-to pattern.

Independent research using anchor-based methods has identified minimal clinically important differences (MCIDs) of ~1.5 points for SMA type 2 and ~2.4 points for SMA type 3. These thresholds are based on historical and real-world data and may indicate that a 2-point change is considered clinically meaningful for patients with SMA.^5,||

^||A retrospective analysis of an untreated population.⁶

RULM score

Secondary endpoint: change from baseline in RULM total score at end of Follow-Up Period 1^2,¶

As a secondary endpoint, patients aged 2 to <18 years old who received ITVISMA reported a numerically higher LS mean change of 2.44 points in Revised Upper Limb Module (RULM) total score from baseline to the end of Follow-Up Period 1, compared to 0.92 for the sham-control group—an LS mean difference of 1.52 points. The results didn't meet the criteria for statistical significance in the study.²

^¶RULM is a 37-point assessment of motor function performance in the upper limbs for individuals with SMA.²

Efficacy by age

Other secondary endpoints: change from baseline in HFMSE and RULM total scores at end of Follow-Up Period 1 in children aged 2 to <5 years²

LS mean change in HFMSE and RULM total scores were numerically higher with ITVISMA compared to sham²

Secondary endpoint results for children aged 2 to <5 years. Scores are also shown for RULM and HFMSE.

Group estimates are displayed as LS mean (SEM) for change from baseline endpoints. Treatment effect is displayed as LS mean (95% CI) for change from baseline endpoints. Results are not statistically significant.²

Exploratory analysis: change from baseline in HFMSE and RULM total scores over 52 weeks in children aged 5 to <18 years²

LS mean change in HFMSE and RULM total scores were numerically higher with ITVISMA compared to sham²

Exploratory and post hoc endpoint results for children aged 5 to 18 years. Scores are also shown for RULM and HFMSE

Post hoc analysis

ITVISMA results across varying baseline characteristics²

HFMSE outcomes across different baseline characteristics in the overall population²

Post hoc analysis and HFMSE score for ITVISMA and the Sham treatment.

Results are not statistically significant.²

ITVISMA was studied in 67 patients for a total of 64 weeks in the STEER study⁷

Period 1 was the basis for the primary analysis of this study. Eligible patients in the ITVISMA group who completed Follow-Up Period 1 and continued into Treatment Period 2 were assessed for an additional 12 weeks of follow-up. Of the 126 patients with SMA who were treated during Treatment Period 1 and completed Follow-Up Period 1, 67 patients treated with ITVISMA and 46 patients from the sham arm continued to Treatment Period 2.^7,#

^#Of the 75 patients who enrolled in this study and were treated with ITVISMA, 2 patients discontinued prior to completing Follow-up Period 1, and 6 did not meet eligibility criteria to enter Treatment Period 2.⁷

HFMSE score to end of Follow-Up Period 2

Data suggest 67 patients experienced an improvement of 2.75 points in HFMSE score with ITVISMA by Week 64 (FAS)⁷

extended64weeks_v2_zolgensma_it_hfmsegraph_desktop_1200

Patients who received ITVISMA in Treatment Period 1 and continued into Follow-Up Period 2 (n=67) saw trends of increased HFMSE score, an LS mean change from baseline of 2.75 points (95% CI: 1.61, 3.88) at 64 weeks.⁷

End of Follow-Up Period 1 is defined as the average of the Week 48 and Week 52 assessments.

RULM score to end of Follow-Up Period 2

Patients reported a numerically higher LS mean change with ITVISMA at Week 64 compared to Week 52^7,**

Patients who received ITVISMA during Treatment Period 1 and continued to Follow-Up Period 2 (n=67) reported a numerically higher LS mean change of 2.93 points in RULM total score at the end of Follow‑Up Period 2, compared to 2.47 points at the end of Follow‑Up Period 1, representing an LS mean difference of 0.46 points.^7,**

**The least square mean change from baseline to the end of Follow-Up Period 1 in RULM score was 2.47, revised from the previously reported interim analysis score of 2.44. The updated number reflects an analysis that included a pre-Period 2 assessment in some patients. There is no change in the interpretation or conclusions of these data. These results are descriptive only.⁷

Even a small difference in motor function can be meaningful for patients with SMA, their caregivers, and their care team. Scarlette lives with SMA and hasn’t received ITVISMA. Individuals shown were compensated for their time.

Review the supportive safety study in previously treated patients

See the data

AAV9, adeno-associated virus serotype 9; CI, confidence interval; FAS, full analysis set; HFMS, Hammersmith Functional Motor Scale; LS, least squares; SD, standard deviation; SE, standard error; SMN, survival motor neuron gene; SMN2, survival motor neuron 2 gene.

With one dose of ITVISMA, patients with SMA achieved significant motor function gains at the end of Study Follow-Up Period 1^1,*