FDA Approves Higher Strength, More Effective Nusinersen Dose for Spinal Muscular Atrophy

Nearly 10 years after its original approval, the FDA has approved a new higher dose strength for nusinersen (Spinraza; Biogen) as a treatment for patients with spinal muscular atrophy (SMA). This new dosing regimen, which is comprised of 50 mg/5 mL and 28 mg/5 mL doses, is designed to deliver a higher concentration of drug through both the loading and maintenance dosing phases, leading to more efficacious results for patients with the disease.¹

The high-dose regimen of nusinersen, expected to become available in the coming weeks, introduces a faster loading schedule for treatment-naïve patients. This approach includes two 50 mg doses given 14 days apart, followed by ongoing maintenance injections of 28 mg every four months. For patients switching from the low-dose regimen, treatment would continue on the same four-month dosing interval after completing a single high-dose loading phase.

The US FDA approval of high dose nusinersen, which comes months after the European Comission granted greenlight, is backed by the phase 2/3 DEVOTE study (NCT04089566). This global, 3-part trial was designed to test safety, pharmacokinetics, and efficacy of this new regimen compared with the originally approved 12 mg regimen. All told, results from the study showed statistically significant improvements in motor function, as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), when compared to a prespecified matched sham (untreated) group from the ENDEAR study* (mean difference: 26.19 points; +15.1 vs. -11.1, P <0.0001).

“I think it’s incredibly exciting,” Crystal Proud, MD, a study author on DEVOTE, told NeurologyLive^® regarding the approval. “We’re nearing 10 years of approval of Spinraza later this year, and our patients have had incredible success over that time period. It’s natural to then say, well, what’s next? Where can we do better?”

Proud, chief of neurology and director of Neuromuscular Medicine at Children’s Hospital of The King’s Daughters, added, “When we look at data from DEVOTE, we see that patients who had previously been treated with 12 mg Spinraza were still able to demonstrate improvements in some of their motor functional scores. There is more potential with maintaining that safety profile, so we’re encouraged by that.”

Nusinersen is an antisense oligonucleotide designed to modify splicing of the SMN2 gene, increasing production of functional survival motor neuron (SMN) protein that is deficient in SMA. By promoting inclusion of exon 7 in SMN2 mRNA, it helps restore motor neuron function and slow disease progression. Its original 2016 approval marked a historic shift in SMA care as the first disease-modifying therapy, transforming a previously fatal, supportive-care–only condition into one with meaningful clinical intervention and improved survival outcomes.²

Biogen previously tried to get approval for higher dose nusinersen in 2025, but was met with a complete response letter, with the FDA 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.³

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As Proud alluded to, the safety profile for this higher strength dose was consistent with its originally approved regimen. In DEVOTE, among patients receiving the high-dose regimen, the most common adverse reactions (≥10% incidence and at least 5% higher than in a matched historical sham-control) included pneumonia, COVID-19, aspiration pneumonia, and malnutrition in those with infantile-onset SMA. Notably, COVID-19 was not identified at the time of the ENDEAR study, which served as the source of the matched sham-control cohort.

With regards to treating, Proud added that “it’s going to be the same cadence of maintenance doses. If we have a patient, for example, who is not currently on Spinraza but wishes to transition to high dose, there is a less burdensome loading phase, which is exciting. But the maintenance phase, that consistent cadence three times per year, is not different. Nothing is different, except for the milligrams, which makes this transition hopefully smoother for our patients that are on the current dosing.”

At the 2024 WMS Annual Congress, investigators reported that patients treated with 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). Reductions in NfL were also observed earlier than with the 12-mg dose, with significant separation emerging by day 64 (nominal P = .0050). By day 302, CHOP-INTEND scores increased by 19.6 points in the higher-dose group and 21.6 points in the 12-mg group (LS mean difference, –1.94; P = .8484), while gains on HINE-2 were more modest and did not reach statistical significance (LS mean difference, 0.58; P = .1734).⁴

The higher-dose regimen was also associated with a 67.8% reduction in the combined risk of death or permanent ventilation compared with sham (HR, 0.322; P = .0006), and a 29.9% reduction relative to the 12-mg regimen (HR, 0.701; P = .2775). These findings aligned with higher survival rates, fewer hospitalizations, and a lower incidence of serious respiratory events. In later-onset patients enrolled in part B, the higher-dose group showed numerically greater improvements on both HFMSE and RULM compared with the 12-mg regimen, with results further supported by matched analyses against sham and 12-mg cohorts from the CHERISH phase 3 trial.

“Over the past decade, Biogen has continued to listen, learn, and innovate to help advance care for people living with SMA,” Priya Singhal, MD, MPH, executive vice president and head of development at Biogen, said in a statement. “With more than 10 years of clinical data on SPINRAZA, the development of the High Dose Regimen reflects both the strength of that foundation and our unwavering commitment to the SMA community to optimize treatment options. We are grateful to the community for their support and contributions toward this milestone.”

REFERENCES
1. FDA Approves New High Dose Regimen of SPINRAZA® (nusinersen) for Spinal Muscular Atrophy. News release. Biogen. March 30, 2026. Accessed March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/fda-approves-new-high-dose-regimen-spinrazar-nusinersen-spinal
2. U.S. FDA Approves Biogen’s SPINRAZA™ (nusinersen), The First Treatment for Spinal Muscular Atrophy. News release. Biogen. December 23, 2016. Accessed March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/us-fda-approves-biogens-spinrazatm-nusinersen-first-treatment
3. Biogen Provides Regulatory Update on High Dose Regimen of Nusinersen. News release. Biogen. September 23, 2025. Accessed March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/biogen-provides-regulatory-update-high-dose-regimen-nusinersen
4. 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 March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/new-higher-dose-nusinersen-efficacy-and-safety-data-presented