Angela Lek, PhD, on the FDA's Approval of High-Dose Nusinersen in SMA

This interview was originally published on our sister site, NeurologyLive®.

“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.”

The FDA approved a new higher-dose formulation of nusinersen (Spinraza; Biogen) for spinal muscular atrophy (SMA) on March 30, 2026, nearly a decade after the therapy first received regulatory clearance. The updated dosing regimen—comprising 50 mg/5 mL and 28 mg/5 mL dose strengths—is intended to deliver greater drug concentrations during both the loading and maintenance phases, with the goal of achieving improved clinical outcomes for patients with the condition.

In the wake of the approval, CGTLive®’s sister site NeurologyLive® spoke with Angela Lek, PhD, chief research officer at MDA, to discuss her perspective on the regulatory decision. Lek contextualized the high-dose regimen within the history of nusinersen development, noting that it builds upon the foundational 2016 approval, which transformed the prognosis for patients living with SMA. She walked through the DEVOTE clinical trial—the 3-part study that formed the clinical basis for the new approval—describing each component in turn: Part A assessed the safety and tolerability of the elevated dose; Part B evaluated efficacy in treatment-naive symptomatic infants relative to matched historical controls drawn from the ENDEAR study; and Part C examined outcomes among patients who transitioned from the established 12-mg regimen to the higher-dose regimen. Across all 3 components, the high-dose regimen was associated with greater improvements in motor function outcomes and quicker reductions in neurofilament biomarker levels, with no new major safety concerns identified in the available data.

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