Regulatory & Policy

FDA approves Biogen's high dose Spinraza regimen for spinal muscular atrophy

The US FDA has approved a high dose regimen of Spinraza (nusinersen) for the treatment of spinal muscular atrophy, the agency and developer Biogen announced on March 30, 2026.

Spinraza, an antisense oligonucleotide that modifies splicing of the SMN2 gene to increase production of functional SMN protein, was the first therapy approved for SMA when it received US FDA clearance in December 2016. The new regimen represents a dose optimization for a drug that has been administered intrathecally to SMA patients across all disease types for nearly a decade. The Muscular Dystrophy Association, which funded the early research by Adrian Krainer at Cold Spring Harbor Laboratory that underpinned the drug's development, noted that the organization has invested more than USD 50 million in SMA research over its history.

The high dose regimen delivers a higher concentration of nusinersen during both the loading and maintenance dosing phases compared to the original regimen. Spinraza is administered via intrathecal injection, requiring repeated lumbar punctures on a maintenance schedule of approximately every four months. The updated regimen was designed to increase drug exposure in the central nervous system while maintaining the safety profile established over the drug's decade of clinical use, the company said. Higher CNS exposure may be particularly relevant in older or heavier patients, where drug distribution with standard dosing may be less optimal.

The approval was based on findings from the DEVOTE study, a clinical trial evaluating the high dose regimen in SMA patients. The source material does not provide detailed efficacy endpoints, patient numbers, or comparative data from DEVOTE. Spinraza's original approval rested on data from the Phase III ENDEAR trial in SMA Type 1, the Phase III CHERISH trial in SMA Types 2 and 3, and the NURTURE study in pre-symptomatic infants. Richard Finkel, an SMA investigator at St. Jude's Children's Research Hospital who participated in several of these trials, said the optimized dosing has "the opportunity to deliver even greater and more sustained benefits to patients across the spectrum of disease."

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The approval arrives in a competitive treatment landscape for SMA that now includes three distinct therapeutic modalities. Novartis's Zolgensma (onasemnogene abeparvovec), a one-time intravenous AAV9 gene therapy delivering a functional copy of the SMN1 gene, was approved in 2019 for patients under two years of age. Genentech/Roche's Evrysdi (risdiplam), a daily oral small molecule SMN2 splicing modifier approved in 2020 for patients aged two months and older, offered the first non-invasive route of administration. Spinraza's intrathecal delivery requirement has been a practical limitation, particularly for patients with scoliosis or prior spinal fusion, and the drug has faced competitive pressure from these alternatives. The dose optimization may represent Biogen's effort to strengthen the clinical rationale for continued or new use of Spinraza in a field where treatment decisions increasingly weigh efficacy, route of administration, and long-term durability. Despite the availability of three approved therapies, incomplete motor recovery remains common, particularly among patients treated after symptom onset, and questions persist around optimal sequencing or combination of available treatments. No combination regimen has received regulatory approval as of March 2026. The expansion of newborn screening programs for SMA across the United States and internationally has shifted treatment increasingly toward pre-symptomatic initiation, where outcomes across all three therapies tend to be most favorable.

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