Content Writer: Author Correction: High-Dose Nusinersen for Spinal Muscular Atrophy – Phase 3 Randomized Trial Correction

An author correction has been issued for a phase 3 randomized trial evaluating high-dose nusinersen in spinal muscular atrophy, refining key efficacy and statistical findings originally reported in February 2026.

The correction, published in Nature Medicine on April 23, 2026, addresses errors in neurodegeneration biomarkers and associated p-values from the DEVOTE trial. In the infantile-onset spinal muscular atrophy cohort, the reduction in neurofilament light chain (NfL) levels compared to the ENDEAR-matched sham group was updated from 30% to 32%, and the nominally significant p-value was revised from 0.0050 to 0.0075.

For the later-onset spinal muscular atrophy cohort, the nominally significant p-value for NfL reduction was corrected from 0.0495 to 0.0047. These changes were made to the HTML and PDF versions of the article, with original figures and tables available in the supplementary information.

The DEVOTE trial evaluated high-dose nusinersen (50-mg loading dose. 28-mg maintenance dose) in treatment-naive individuals with spinal muscular atrophy. Part B of the trial randomized 75 participants in a 2:1 ratio to receive either high-dose nusinersen or the standard 12/12 mg regimen. The primary endpoint assessed the 6-month change in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score in infantile-onset participants compared to matched sham controls from the ENDEAR trial.

At day 183, participants receiving high-dose nusinersen showed a significant improvement of +15.1 points in CHOP-INTEND scores, while the matched sham group experienced a worsening of -11.1 points. The between-group difference was 26.19 points (95% confidence interval: 20.7 to 31.74), with statistical significance confirmed via joint-rank test (P < 0.0001).

The trial included a supportive open-label cohort (Part C) of nusinersen-experienced individuals who had received the standard 12/12 mg dose for over one year. Biomarker analysis, including neurodegeneration markers like NfL, formed part of the secondary outcomes assessed across all trial parts.

Spinal muscular atrophy is a genetic neuromuscular disorder characterized by progressive muscle weakness and atrophy due to loss of motor neurons. Nusinersen, an antisense oligonucleotide, modifies splicing of the SMN2 gene to increase production of survival motor neuron protein. While disease-modifying therapies have improved outcomes, residual neurodegeneration remains a challenge in some patients.

The author correction ensures accuracy in reporting the trial’s biomarker findings, which support the potential of high-dose nusinersen to slow neurodegeneration. The revised p-values, while still indicating nominal significance in certain analyses, reflect updated statistical interpretation without altering the primary clinical outcome.

No additional changes were reported to the trial’s safety profile, participant demographics, or primary efficacy results. The correction focuses exclusively on refining neurodegeneration data presentation in Figures 2, Table 2, and Extended Data Figure 4 of the original publication.

The updated article is available through Nature Medicine with the digital object identifier doi:10.1038/s41591-026-04415-5. Readers are directed to the supplementary information for comparison between original and corrected versions of the affected figures and tables.