Positive study shows potential of higher dose nusinersen to improve SMA treatment

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Biogen has announced positive results from its phase 2/3 DEVOTE study, which evaluated a higher dose regimen of nusinersen (SPINRAZA; Biogen) in infants with spinal muscular atrophy (SMA). The data revealed statistically significant improvements in motor function among participants receiving the investigational regimen, compared to a prespecified sham control group. Biogen plans to submit the higher dose regimen of nusinersen for regulatory approval.

Study design

The DEVOTE study focused on treatment-naïve, symptomatic infants, investigating whether a more intense dosing schedule of nusinersen could provide superior clinical outcomes. Nusinersen, is an already established treatment for SMA, with the approved regimen consisting of an initial loading phase followed by regular maintenance doses. The new investigational regimen delivers 2 50-mg doses 14 days apart during the loading phase, followed by a 28-mg maintenance dose every 4 months.

The DEVOTE study was conducted across 42 global sites and enrolled 145 patients with different SMA types. Part B, the pivotal phase, enrolled infants with infantile-onset SMA, while the broader study will also explore outcomes in later-onset cohorts. Detailed results are expected to be shared at upcoming medical conferences.

Results

Part B of the study enrolled 75 infants with infantile-onset SMA and compared the investigational higher dose of nusinersen to a sham control group from the earlier ENDEAR study. The primary endpoint measured improvements in motor function using the Children’s Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) at 6 months. Results showed a significant improvement in motor function in those receiving the higher dose, with a least squares mean difference of 26.19 (p<0.0001).

The higher dose also demonstrated positive trends when compared to the current 12-mg dosing regimen, with benefits observed across key efficacy and biomarker measures. Biogen emphasized that the regimen was generally well tolerated, with a lower incidence of serious adverse events (60%) compared to the 12-mg regimen (72%). Common adverse effects were consistent with both SMA and nusinersen’s known safety profile.

Conclusion

“The encouraging topline results from DEVOTE show that the higher dose regimen can slow neurodegeneration faster, as shown by greater reductions in neurofilament at day 64 relative to the approved dose,” said Stephanie Fradette, PharmD, head of Biogen's Neuromuscular Development Unit. “Over time, the higher dose regimen led to meaningful clinical benefit in infants with symptomatic SMA. We look forward to sharing the detailed results with the SMA community and health authorities.”

She added, “While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of SPINRAZA established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety.”

Reference:

Biogen Announces Positive Topline Results from Study of Higher Dose Regimen of Nusinersen, Showing Significant Benefit in Treatment of SMA. Biogen. September 4, 2024. Access September 10, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-announces-positive-topline-results-study-higher-dose