FDA Approves High-Dose Nusinersen for SMA

Hope is on the horizon for adult and pediatric patients living with spinal muscular atrophy (SMA), an inherited and progressive neuromuscular disorder concentrated in the loss of lower motor neurons in the spinal cord, for which there is currently no cure.¹ The FDA has approved high-dose nusinersen (Spinraza; Biogen) for both the loading and maintenance dosing phases of treatment.² Compared with low-dose nusinersen of 12 mg, high-dose nusinersen comprises doses of 28 mg/5 mL and 50 mg/5 mL.

Data from the 3-part phase 2/3 interventional DEVOTE study (NCT04089566) among 145 patients supported Biogen’s application and this approval.¹ Part A was the initial safety and tolerability assessment, part B saw patients randomly assigned 2:1 to receive 50/28 mg (n = 50) or 12/12 mg (n = 25) nusinersen, and part C comprised an open-label cohort of treatment-experienced patients aged 4 to 65 years³ who had been receiving low-dose nusinersen for a median of 3.9 years.⁴ Patients 7 days and older with genetically documented SMA were eligible for inclusion.⁵ The primary end point was 6-month change from baseline in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) with nusinersen compared with a prespecified matched sham control group from the phase 3, randomized, double-blind, sham-procedure, controlled ENDEAR study (NCT02193074).

The patients who received nusinersen exhibited a 15.1-point improvement on CHOP-INTEND vs a disease worsening of 11.1 points for those in the control cohort (difference, 26.19; 95% CI, 20.7-31.74; P < .0001),⁴ with a safety profile for the high-dose regimen consistent with that of the low-dose regimen.² It is administered via intrathecal bolus injection directly into the cerebrospinal fluid,⁶ with a typical procedure time of 15 minutes and a total visit time of several hours to account for monitoring labs and postprocedure observation,⁷ owing to increased risks of bleeding complications and kidney damage with the potential to be fatal.²

“Nearly 10 years ago, the approval of Spinraza marked a turning point in SMA care and changed what the community believed was possible, with Biogen becoming a trusted partner for thousands of people living with SMA. Today’s approval of high-dose Spinraza makes progress in addressing unmet needs of the SMA community,” said Kenneth Hobby, president of Cure SMA, in a statement.²

With potential availability in as soon as a few weeks, the 2 new doses mean an accelerated loading phase for treatment-naive patients. After two 50 mg/5 mL doses are given 2 weeks apart, treatment-naive patients will continue on a maintenance regimen of 28-mg/5-mL doses every 4 months on an outpatient basis.⁷ For patients currently on the low-dose regimen, after the initial 50-mg/5-mL loading doses, they would transition to the higher doses on their existing dosing schedule.

Pneumonia, COVID-19, pneumonia aspiration, and malnutrition in patients with infantile-onset SMA were the most common adverse reactions, each seen in at least 10% of patients who received high-dose nusinersen in the DEVOTE study. These also occurred at least 5% more often than those seen in the control cohort from the ENDEAR study.

In February, Nature Medicine published findings from DEVOTE that showed high-dose nusinersen was safe and effective irrespective of age, treatment history, and baseline functional status.^3,4 Beyond the positive data reported above, the authors highlighted that patients experienced a mean 1.8-point increase on the Hammersmith Functional Motor Scale – Expanded and a 1.2-point increase on the Revised Upper Limb Module from baseline by day 302.

References

1. Spinal muscular atrophy (SMA). Cleveland Clinic. Updated June 6, 2024. Accessed March 30, 2026. https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma
2. 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
3. Nature Medicine published results from the pivotal DEVOTE study of high-dose regimen of nusinersen in spinal muscular atrophy. News release. Biogen. February 4, 2026. Accessed March 30, 2026. https://investors.biogen.com/news-releases/news-release-details/nature-medicine-publishes-results-pivotal-devote-study-high-dose
4. Finkel RS, Crawford TO, Mercuri E, et al. High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial. Nat Med. 2026 Mar;32(3):1095-1104. doi:10.1038/s41591-025-04193-6
5. Study of nusinersen (BIIB058) in participants with spinal muscular atrophy (DEVOTE). ClinicalTrials.gov. Updated June 5, 2025. Accessed March 30, 2026. https://clinicaltrials.gov/study/NCT04089566
6. Stewart J. How is Spinraza administered? Drugs.com. Updated January 23, 2025. Accessed March 30, 2026. https://www.drugs.com/medical-answers/how-spinraza-administered-3218023/
7. Nusinersen (Spinraza) for spinal muscular atrophy treatment. Children’s Hospital of Philadelphia. Accessed March 30, 2026. https://www.chop.edu/treatments/nusinersen-spinraza-spinal-muscular-atrophy-treatment