Studies at MDA 2026 Evaluate High-Dose Spinraza for Spinal Muscular Atrophy
Key Takeaways
- Treatment with high-dose Spinraza was associated with lower risk of death or permanent ventilation in people with spinal muscular atrophy.
- Motor function improvements observed during the DEVOTE study were maintained through 29 months of follow-up in the ONWARD study.
- High-dose Spinraza was generally well tolerated, with a safety profile consistent with the standard dosing regimen.
Treatment with high-dose Spinraza (nusinersen; Biogen, Cambridge, MA) was associated with sustained improvements in motor function and survival outcomes in people with spinal muscular atrophy (SMA). Interim integrated results from the phase 2/3 DEVOTE (NCT04089566) and phase 3 ONWARD (NCT04729907) studies were presented at the 2026 Muscular Dystrophy Association Clinical and Scientific Conference.
DEVOTE enrolled 99 treatment-naive participants with infantile-onset (aged ≤6 months; n=75) and later-onset (aged 2 to <10 years; n=24) SMA who were randomized 2:1 to high-dose Spinraza (loading doses, 50 mg; maintenance doses, 28 mg) or the standard 12/12 mg regimen (loading doses, 12 mg; maintenance doses, 12 mg). In the ongoing, open-label ONWARD extension, participants initially treated with the 12/12 mg regimen in DEVOTE transitioned to high-dose Spinraza (n=25), whereas those who received high-dose Spinraza in DEVOTE continued high-dose treatment (n=50). Functional end points were assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Infant Neurological Examination Section 2 (HINE-2), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module (RULM).
Key findings at 29 months include:
- In infantile-onset participants, mean change in CHOP-INTEND total score was +28.4 points at month 29 following high-dose Spinraza treatment, compared with +20.7 points in the 12/12 mg group during DEVOTE.
- Mean change from baseline in HINE-2 total score was +13.8 points in the high-dose group.
- In later-onset participants receiving high-dose Spinraza, mean change from baseline was +4.0 points for HFMSE and +3.5 points for RULM.
- Event-free survival (death or permanent ventilation) was higher among participants who received high-dose Spinraza starting at study initiation, compared with those who initially received the 12/12 mg regimen and later transitioned to high-dose therapy (HR, 0.593; 95% CI, 0.294 to 1.194).
- Plasma neurofilament light chain (NfL) levels declined rapidly following high-dose initiation in both cohorts and remained low.
- The high-dose regimen was well tolerated, with an adverse event profile consistent with standard-dose Spinraza; no participants discontinued due to an adverse event.
Source: Crawford TO, Finkel RS, Garcia Romero MM, et al; on behalf of the DEVOTE Study Group. Exploring high dose nusinersen in spinal muscular atrophy: integrated results from the DEVOTE Part B and ONWARD studies. Poster presented at: 2026 MDA Clinical and Scientific Conference; March 8-11, 2026; Orlando, Florida, USA.