Context, Evidence, and Ongoing Questions Regarding the FDA's Approval of High-Dose Nusinersen in SMA: Angela Lek, PhD

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I think it's encouraging to see that Biogen wasn't content with the status quo when it came to the established clinical dose of the drug. Even after such a transformative first approval, they continue to ask whether we could do better for the patients. And that's really how progress happens in medicine.

On March 30, 2026, the FDA has approved a new higher dose strength for nusinersen (Spinraza; Biogen) as a treatment for patients with spinal muscular atrophy (SMA), almost 10 years after the therapy’s original approval. The 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, with the intent of enabling more efficacious results for patients with the disease.

Following the approval, NeurologyLive® sat down with Angela Lek, PhD, MDA's chief research officer, to hear her perspective on the FDA’s decision. Lek reviewed how the high-dose regimen builds on the original 2016 approval of nusinersen, which fundamentally altered the prognosis for SMA. She outlined the DEVOTE trial, a 3-part clinical trial that supported the high-dose approval: Part A evaluated safety and tolerability; Part B examined efficacy in treatment-naive, symptomatic infants versus matched historical controls from the ENDEAR study; and Part C assessed outcomes in patients switched from the standard 12-mg dose to the high-dose regimen. Across these components, higher dosing was associated with improved motor outcomes and more rapid reductions in neurofilament biomarkers, without new major safety signals in the data presented.

Throughout the discussion, Lek emphasized that high-dose nusinersen represents an incremental optimization, not a replacement of the original regimen, and underscored the need for individualized treatment decisions based on age, disease stage, prior therapies, and patient/family goals. She highlighted several unanswered questions, including durability and magnitude of benefit over time and which patients are most likely to benefit from switching. Finally, Lek stressed the importance of real-world data and discussed the Muscular Dystrophy Association’s evolving MOVR neuromuscular observational registry, designed to capture longitudinal outcomes and inform future clinical decision-making and research as SMA therapies and combination approaches continue to evolve.

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