General Information

Spinraza (nusinersen) is a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide.

Spinraza is specifically indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

Spinraza is supplied as a solution to be administered intrathecally. The recommended dosage is 12 mg (5 mL) per administration. Initiate Spinraza treatment with 4 loading doses. The first three loading doses should be administered at 14-day intervals. The 4th loading dose should be administered 30 days after the 3rd dose. A maintenance dose should be administered once every 4 months thereafter.

Missed Dose: If a loading dose is delayed or missed, administer Spinraza as soon as possible, with at least 14-days between doses and continue dosing as prescribed. If a maintenance dose is delayed or missed, administer Spinraza as soon as possible and continue dosing every 4 months.

Clinical Results

FDA Approval

The FDA approval of Spinraza was based on ENDEAR, a randomized, double-blind, sham-controlled phase III study in 121 patients with infantile-onset (most likely to develop Type 1) SMA. At a planned interim analysis of ENDEAR, a greater percentage of infants treated with Spinraza achieved a motor milestone response compared to those who did not receive treatment (40% versus 0%; p<0.0001) as measured by the Hammersmith Infant Neurological Examination (HINE). Additionally, a smaller percentage of patients on Spinraza died (23%) compared to untreated patients (43%). Data from the other efficacy endpoints analyzed were consistently in favor of infants who received treatment.

The results of the controlled trial in infantile-onset SMA patients were supported by open-label uncontrolled trials conducted in symptomatic SMA patients who ranged in age from 30 days to 15 years at the time of first dose, and in presymptomatic patients, who ranged in age from 8 days to 42 days at the time of first dose. The patients in these studies had or were likely to develop Type 1, 2, or 3 SMA. Some patients achieved milestones such as ability to sit unassisted, stand, or walk when they would otherwise be unexpected to do so, maintained milestones at ages when they would be expected to be lost, and survived to ages unexpected considering the number of SMN2 gene copies of patients enrolled in the studies.

Mechanism of Action

Spinraza (nusinersen) is a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide. It was designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, Spinraza was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein.