High-Dose Nusinersen Gains European Commission Approval for Spinal Muscular Atrophy

Biogen recently announced that the European Commission (EC) has granted marketing authorization for a high-dose, potentially more efficacious regimen of nusinersen (Spinraza) for patients with 5q spinal muscular atrophy (SMA).¹

The newly approved high-dose regimen includes a more rapid loading phase consisting of two 50 mg loading doses administered 14 days apart, followed by 28-mg maintenance doses every 4 months thereafter. Notably, patients transitioning from the previously approved 12-mg regimen will receive a single 50-mg dose in place of their next scheduled 12-mg dose, followed by 28-mg maintenance dosing every four months.

This EC approval is based on data from a previous three-part, Phase 2/3 DEVOTE study (NCT04089566) and its ongoing long-term extension. Clinical data from the pivotal cohort of the study showed that treatment-naïve, symptomatic infants who received the high-dose regimen of nusinersen experienced statistically significant improvements in motor function as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), compared with a prespecified matched untreated cohort from the ENDEAR study (mean difference, 26.19 points; +15.1 vs −11.1; P <0.0001).

Motor function improvements were also observed in the DEVOTE open-label cohort, which included individuals across a range of ages and SMA types who transitioned from the low-dose regimen. Participants in this cohort experienced a mean improvement of 1.8 points (SD, 3.99) on the Hammersmith Functional Motor Scale–Expanded from baseline to day 302.

“Since its approval in the European Union in 2017, nusinersen has helped set a new standard in patient care and treated more than then 10,000 infants, children, teens and adults worldwide,” Priya Singhal, MD, MPH, executive vice president and head of development at Biogen, in a statement. “We are proud to introduce the high-dose regimen of nusinersen, which we have developed to address the evolving needs of individuals living with SMA, and are deeply committed to bringing it to the European SMA community as quickly as possible. We are grateful for all of the contributions of the SMA community who made today’s approval possible.”¹

Throughout the DEVOTE study, high-dose regimen was generally well tolerated, with reported adverse events (AEs) consistent with SMA and the known safety profile of nusinersen. Notably, no new safety concerns were observed with continued use of high-dose nusinersen in the long-term extension study.

In DEVOTE, the most common AEs that occurred in at least 10% of participants treated with the high-dose regimen and occurred at least 5% more frequently than the matched sham group were pneumonia, COVID-19, pneumonia aspiration, and malnutrition. Special warnings and precautions for use of nusinersen include adverse reactions as a part of the lumbar puncture procedure, low platelet counts and blood clotting abnormalities, renal toxicity and hydrocephalus.

“The DEVOTE results provide encouraging evidence that this new dosing option could deliver meaningful treatment outcomes with a safety profile generally consistent with the 12 mg dosing regimen,” said Eugenio Mercuri, MD, PhD, professor of pediatric neurology at the Catholic University in Rome, Italy, in a statement.¹ “I have witnessed the remarkable strides that have been made in treating SMA, but it is clear challenges remain. The European Commission approval of the high-dose regimen of nusinersen is an important step toward addressing those challenges and advancing how we care for people living with SMA.”¹

At the 2024 WMS Annual Congress, investigators reported that patients receiving the higher-dose regimen achieved a 94% reduction in plasma neurofilament light chain (NfL) levels from baseline to day 183, compared with a 30% reduction in the sham group (P < .0001). Declines in NfL also occurred more quickly than with the 12-mg dose, with significant separation observed as early as day 64 (nominal P = .0050). By day 302, CHOP-INTEND scores increased by 19.6 points in the higher-dose arm and 21.6 points in the 12-mg arm (LS mean difference, –1.94; P = .8484), while improvements in HINE-2 were smaller and did not reach statistical significance (LS mean difference, 0.58; P = .1734).

The higher-dose regimen also reduced the combined risk of death or permanent ventilation by 67.8% versus sham (HR, 0.322; P = .0006) and by 29.9% compared with the 12-mg regimen (HR, 0.701; P = .2775). These outcomes were consistent with higher survival rates, fewer hospitalizations, and a lower incidence of serious respiratory events. Among later-onset patients in part B, the higher-dose arm demonstrated numerically greater improvements on both the HFMSE and RULM motor scales compared with the 12-mg regimen, with findings further supported by matched comparisons to sham and 12-mg controls from the CHERISH phase 3 study.

In late 2025, the FDA handed Biogen a complete response letter (CRL) for the higher dose strength, citing updates needed to the Chemistry Manufacturing and Controls module of the supplemental new drug application (sNDA). At the time, the agency did not cite any deficiencies in the clinical data presented in the package and offered potential resolutions to recorrect the submission.

REFERENCES
1. Biogen Receives European Commission Approval for High Dose Regimen of SPINRAZA® (nusinersen) for Spinal Muscular Atrophy. Biogen. News Release. January 12, 2026. Accessed January 13, 2026.
2. New Higher Dose Nusinersen Efficacy and Safety Data Presented at World Muscle Society Congress, Highlight Potential to Maximize Benefit of Nusinersen in SMA. News Release. Biogen. Published October 8, 2024. Accessed January 13, 2026. https://investors.biogen.com/news-releases/news-release-details/new-higher-dose-nusinersen-efficacy-and-safety-data-presented
3. Biogen Provides Regulatory Update on High Dose Regimen of Nusinersen. News release. Biogen. September 23, 2025. Accessed January 13, 2026. https://investors.biogen.com/news-releases/news-release-details/biogen-provides-regulatory-update-high-dose-regimen-nusinersen