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Treatment-naive
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Treatment-experienced
SPINRAZA FOR INFANTILE- AND LATER-ONSET SMA
DEVOTE
A 3-part study evaluating the safety and efficacy of High Dose Regimen of SPINRAZA1,2
DEVOTE Part B1,2
Study overview: A phase 3, multicenter, double-blind, randomized (2:1) trial of High Dose SPINRAZA and Low Dose SPINRAZA. The cohort with infantile-onset SMA was compared with a matched group of participants from ENDEAR who had received a sham procedure
Study duration: 302 days
Participants: All had symptomatic SMA and were treatment-naive
Primary endpoint: Change in CHOP INTEND at Day 183 in patients with infantile-onset SMA receiving SPINRAZA High Dose Regimen as compared to an ENDEAR-matched sham group
Select secondary outcomes measured (infantile-onset cohort): HINE-2, plasma NfL, event-free survival, overall survival
Study limitation: Devote Part B was not powered to show superiority of High Dose SPINRAZA over Low Dose SPINRAZA
Safety: The most common adverse reactions in the High Dose Regimen that occurred in ≥10% of SPINRAZA-treated patients and occurred ≥5% more frequently than in historic-matched sham-control patients from ENDEAR were pneumonia, COVID-19, pneumonia aspiration, and malnutrition in patients with infantile-onset SMA. COVID-19 was not discovered at the time of ENDEAR
CHOP INTEND, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders; HINE-2, Hammersmith Infant Neurological Exam Section 2; NfL, neurofilament light chain; SMA, spinal muscular atrophy.
DEVOTE Part B study design1,2
Administered volume of single-use vials of all strengths was 5 mL.
SMN2, survival motor neuron 2.
INFANTILE-ONSET
Baseline demographics between groups were balanced; DEVOTE patients presented with earlier symptom onset and more severe disease severity1,2
†Prespecified ENDEAR-matched sham group based on disease duration and baseline CHOP INTEND score.
INFANTILE-ONSET
SPINRAZA High Dose Regimen significantly improved CHOP INTEND scores vs matched sham control1,2
Mean Change in CHOP INTEND from baseline to Month 6
Adapted from Finkel RS, et al. Nat Med. 2026.
PRIMARY ENDPOINT: CHOP INTEND
With High Dose SPINRAZA, scores improved by
+15.1 points from baseline to Month 6 vs -11.1 points for sham control
The primary analysis was performed using ranking based on the CHOP INTEND score at Month 6 or day of death and fitting an ANCOVA model adjusting for disease duration and baseline CHOP INTEND to determine the difference in ranks via the joint-rank test. MI was used to impute missing data.
‡Least-squares mean difference.
ANCOVA, analysis of covariance; LSM, least-squares mean; MI, multiple imputation; SE, standard error.
INFANTILE-ONSET
The safety of High Dose SPINRAZA was generally consistent with the known safety of Low Dose SPINRAZA2,4
Adverse reactions that occurred in ≥5% of High Dose SPINRAZA patients and at least 5% more frequently or ≥2 times as frequently than matched sham control1
Select Safety Findings from DEVOTE in High Dose Regimen1
Warnings and Precautions1
Thrombocytopenia and coagulation abnormalities: Increased risk for bleeding complications; testing required at baseline and before each dose as clinically needed.
Renal toxicity: Quantitative spot urine protein testing required at baseline and prior to each dose.
Select Safety Findings from DEVOTE2
Adapted from Finkel RS, et al. Nat Med. 2026.
Each subject was counted once in each category.
§Each subject was counted once at maximum severity.
||Related as assessed by investigator.
¶AEs and SAEs occurring in the investigational treatment arms (Part B High Dose Regimen and Low Dose Regimen arms and Part C).
AE, adverse event; SAE, serious adverse event.
SPINRAZA FOR INFANTILE- AND LATER-ONSET SMA
DEVOTE
A 3-part study evaluating the safety and efficacy of High Dose Regimen of SPINRAZA1,2
DEVOTE Part C2
Study overview: An open-label observational study of children and adults who transitioned from Low Dose SPINRAZA to High Dose SPINRAZA
Study duration: 302 days
Participants: 40 patients with infantile- and later-onset SMA
Select outcomes measured: Safety, tolerability, HFMSE, RULM
Study limitations:
- DEVOTE Part C was observational in design and only included a treatment group
- DEVOTE Part C lacked a control or comparator group and endpoints were considered supportive; therefore, findings may not be sufficient on their own to establish the effectiveness of a given treatment
HFMSE, Hammersmith Functional Motor Scale—Expanded; RULM, Revised Upper Limb Module; SMA, spinal muscular atrophy.
DEVOTE Part C study design1,2
At baseline, patients were previously treated with Low Dose Regimen of SPINRAZA for a median of 3.9 years2,4
SMN2, survival motor neuron 2.
Motor function increases reported in patients receiving High Dose Regimen of SPINRAZA after median 3.9 years on Low Dose SPINRAZA2
In adults (n=24), the mean score increased by 2.3 points on HFMSE and 0.9 points on
RULM at Month 10 from baseline2
Study Month 0 is baseline. Observed data and mean change are shown. Two participants did not have HFMSE/RULM scores collected at baseline and were not included in the analysis.
HFMSE, Hammersmith Functional Motor Scale—Expanded; RULM, Revised Upper Limb Module; SE, standard error.
>75% of patients (29/38) experienced an increase or no change in HFMSE scores after transitioning to High Dose SPINRAZA4
Adapted from Finkel et al. Presentation at CureSMA 2025.
Based on individual patient data, no conclusions can be drawn.
No participants had a max score (66) at baseline. Participants with baseline and Month 10 values were included.
†Participants with infantile-onset SMA.
‡Participants experienced fracture of the femur.
~90% of patients (33/37) experienced an increase or no change in RULM after transitioning to High Dose SPINRAZA4
Adapted from Finkel et al. Presentation at CureSMA 2025.
Based on individual patient data, no conclusions can be drawn.
Patients with baseline and Month 10 values were included.
§Participants with infantile-onset SMA.
||Participant experienced fractures of the femur.
The safety of High Dose SPINRAZA was generally consistent with the known safety of Low Dose SPINRAZA2,5
Select safety findings from DEVOTE in High Dose SPINRAZA
Each subject was counted once in each category.
¶Infantile-onset (n=2); later-onset (n=38).
**Each subject was counted once at maximum severity..
††.Related as assessed by investigator.
‡‡ .AEs and SAEs occurring in the investigational treatment arms (Part B High Dose Regimen and Low Dose Regimen arms and Part C).
AE, adverse event; SAE, serious adverse event..