High-Dose Nusinersen Slows Neurodegeneration in SMA Patients, Study Shows

Results from a Phase II/III study (DEVOTE) published in Nature Medicine provide new evidence supporting the clinical benefit of a high-dose regimen of nusinersen in people living with spinal muscular atrophy (SMA) (1). The study evaluated a regimen consisting of 50 mg loading doses followed by 28 mg maintenance dosing and demonstrated functional improvements and faster biomarker response compared with the approved 12 mg regimen, as announced by Biogen on Feb. 4, 2026 (2).

In November 2025, Biogen received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use for the higher-dose regimen of nusinersen, which then received European Commission marketing authorization on Jan. 12, 2026 (3,4).

Nusinersen is an antisense oligonucleotide developed by Biogen and marketed as Spinraza. It is approved globally for the treatment of SMA. The study findings add to ongoing efforts to assess whether higher dosing strategies may further improve outcomes across a broad range of patients, including those with different ages, disease severity, and prior treatment exposure.

How did biomarker data inform neurodegeneration outcomes?

A key differentiating finding from the Phase II/III study was the effect of higher dosing on neurofilament, a biomarker associated with neurodegeneration. Treatment with the high-dose regimen resulted in a more rapid reduction in neurofilament levels compared with the 12 mg regimen, suggesting earlier slowing of neurodegenerative processes.

“One of the most notable changes seen with the higher dose regimen was a more rapid reduction in neurofilament, a marker of neurodegeneration,” said Richard Finkel, MD, director of the Center for Experimental Neurotherapeutics at St. Jude Children’s Research Hospital, in a company press release (2). “In DEVOTE, treatment with the high-dose regimen led to improvement across important domains like motor and bulbar function, respiratory health and hospitalizations, and survival.”

What did the study show in previously treated patients?

In the open-label Part C cohort, 40 participants aged 4 to 65 years transitioned from the 12 mg regimen to the high-dose regimen after a median of 3.9 years of prior treatment. Participants received one 50 mg dose four months after their last 12 mg dose, followed by 28 mg maintenance dosing every four months.

After transitioning, participants demonstrated mean improvements of 1.8 points on the Hammersmith Functional Motor Scale–Expanded and 1.2 points on the Revised Upper Limb Module at Day 302, indicating functional gains in individuals with established disease and long-term prior treatment (1,2).

“The publication of the DEVOTE data are an important step in our commitment to bring the high dose regimen of nusinersen to people living with SMA as quickly as possible,” said Stephanie Fradette, PharmD, head of the Neuromuscular Development Unit at Biogen, in the release (2).

How did safety compare with existing dosing?

The safety profile of the high-dose regimen was broadly consistent with that of the 12 mg regimen. In the infantile-onset cohort, the most common adverse events included pneumonia, respiratory failure, pyrexia, COVID-19, and upper respiratory tract infection. Serious adverse events occurring in at least 10% of participants included pneumonia, aspiration pneumonia, and respiratory failure (2).

The high-dose regimen of nusinersen, already approved in the European Union and Japan, is currently under review by FDA. A Prescription Drug User Fee Act action date is set for April 3, 2026.

References

1. Finkel, R. S., Crawford, T. O., Mercuri, E. et al. High-dose Nusinersen for Spinal Muscular Atrophy: A Phase 3 Randomized Trial. Nat. Med. 2026. DOI: 10.1038/s41591-025-04193-6
2. Biogen. Nature Medicine Publishes Results from the Pivotal DEVOTE Study of High-Dose Regimen of Nusinersen in Spinal Muscular Atrophy. Press Release. Feb. 4, 2026.
3. Biogen. High Dose Regimen of Nusinersen Receives Positive CHMP Opinion for the Treatment of Spinal Muscular Atrophy. Press Release. Nov. 17, 2025.
4. Biogen. Biogen Receives European Commission Approval for High Dose Regimen of SPINRAZA (nusinersen) for Spinal Muscular Atrophy. Press Release. Jan. 12, 2026.