FDA Approves High-Dose Regimen of Nusinersen for Spinal Muscular Atrophy
Key Clinical Summary
- The US Food and Drug Administration (FDA) approved a new high-dose regimen of nusinersen (SPINRAZA) for the treatment of spinal muscular atrophy (SMA) based on phase 2/3 DEVOTE trial data.
- Treatment-naïve infants showed significant motor improvement versus sham controls (CHOP-INTEND mean difference: +26.19 points; p < 0.0001).
- Safety profile was consistent with the established low-dose regimen, with pneumonia and respiratory events among common adverse reactions.
The US Food and Drug Administration (FDA) has approved a new high-dose regimen of Biogen Inc’s nusinersen (SPINRAZA) for the treatment of spinal muscular atrophy (SMA). The approval was supported by data from the 3-part, phase 2/3 DEVOTE study, as well as a decade of clinical data backing a lower-dose regimen.
Regulatory Context
The low-dose regimen of nusinersen (12 mg/5 mL) was approved by the FDA in 2016 for the treatment of SMA in adult and pediatric patients. The newly approved regimen includes 50 mg/5 mL loading doses and 28 mg/5 mL maintenance doses. For treatment-naïve patients, the regimen involves two 50 mg loading doses administered 14 days apart, followed by maintenance dosing every 4 months. Patients transitioning from the 12 mg regimen receive a single high-dose loading phase before continuing maintenance dosing at 4 month-intervals.
Approval was supported by data from the DEVOTE trial, a randomized, controlled, dose-escalating study evaluating the efficacy, safety, tolerability, and pharmacokinetics of nusinersen at 50/28 mg. The study included 145 participants across age groups and SMA types.
In the study’s cohort of symptomatic, treatment-naïve infants, high-dose nusinersen demonstrated significant improvement in motor function, measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) when compared to a matched untreated group from the ENDEAR study, yielding a mean difference of 26.19 points; (p < 0.0001).
The safety profile of the high-dose regimen was also consistent with that of the 12 mg regimen. Common adverse reactions included pneumonia, COVID-19, pneumonia aspiration, and malnutrition in infantile-onset SMA.
Clinical Implications
The approval introduces a higher-dose therapeutic option that may address unmet needs in SMA management, particularly for patients requiring enhanced efficacy or faster clinical response. The accelerated loading phase could be clinically relevant in rapidly progressing infantile-onset disease, where early motor gains are critical.
Clinicians must weigh benefits against known risks, including respiratory complications and potential renal or bleeding concerns. Monitoring protocols, including laboratory testing for renal function and coagulation, remain essential.
Expert Commentary
“Optimizing the dose of nusinersen builds on a therapy that we already know can change lives,” said Richard Finkel, MD, director, Center for Experimental Neurotherapeutics (CENT), St. Jude Children’s Research Hospital, in a press release. “I believe high dose Spinraza will play an important role in the future of SMA care.”
