The US Food and Drug Administration approved a higher-dose regimen of nusinersen (SPINRAZA) for the treatment of spinal muscular atrophy in pediatric and adult patients, introducing a revised dosing schedule with increased drug exposure during loading and maintenance phases.
The high-dose regimen includes two 50 mg loading doses administered 14 days apart, followed by maintenance doses of 28 mg every 4 months. Patients transitioning from the previously approved 12 mg regimen may receive a single high-dose loading phase and then continue maintenance dosing at 4-month intervals. This approach builds on more than a decade of clinical data supporting nusinersen and maintains an established safety profile.
Approval was based on data from the phase 2/3 DEVOTE study, a randomized, controlled, dose-escalation trial evaluating safety, tolerability, pharmacokinetics, and efficacy in patients with spinal muscular atrophy. In the pivotal cohort of treatment-naïve infants with symptomatic disease, patients receiving the high-dose regimen demonstrated statistically significant improvement in motor function compared with a matched untreated group from a prior trial. Motor function was assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, with findings indicating statistically significant improvement over 6 months.
The safety profile of the high-dose regimen was consistent with that of the lower-dose regimen. The most common adverse events included pneumonia, coronavirus disease 2019, aspiration pneumonia, and malnutrition among patients with infantile-onset disease. Monitoring for bleeding complications and kidney damage is recommended, with laboratory testing performed prior to and during treatment.
Nusinersen is delivered via intrathecal injection by health care professionals trained in performing lumbar puncture procedures. The therapy is indicated for the treatment of spinal muscular atrophy in both pediatric and adult patients. The high-dose regimen has received approval in multiple regions, including the EU, Switzerland, and Japan, and is expected to become available in the US in the coming weeks.
Source: Biogen
