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

HFMSE score

Primary endpoint was met:

Clinically meaningful and statistically significant improvement was seen in HFMSE 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^1,2

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

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
^§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 indicate that a 2-point change may be considered clinically meaningful for patients with SMA.^5,6

RULM score

Secondary endpoint: change from baseline in RULM total score at end of Follow-Up Period 1²

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

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 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

Even small improvements in motor function can be meaningful for patients with SMA, their caregivers, and their care team.

Review the supportive safety study in previously treated patients

See the data

AAV9, adeno-associated virus serotype 9; CI, confidence interval; HFMS, Hammersmith Functional Motor Scale; HFMSE, Hammersmith Functional Motor Scale — Expanded; LS, least squares; MCID, minimal clinically important difference; MMRM, mixed model repeated measures; RULM, Revised Upper Limb Module; SD, standard deviation; SE, standard error; SEM, standard error of mean; SMA, spinal muscular atrophy; SMN, survival motor neuron gene; SMN2, survival motor neuron 2 gene.

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

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