Spinraza (nusinersen) is an antisense oligonucleotide (ASO) that consists of small pieces of synthetic material that bind ribonucleic acid (RNA). The therapy, which was developed to treat infants and children with spinal muscular atrophy, targets the SMN2 gene and converts it to a SMN1 gene, which then binds to the RNA template made by SMN2 and enhances the inclusion of exon 7 into the SMN (survival motor neuron) protein, increasing its production.1
Spinraza became the first treatment approved by the U.S. Food and Drug Administration (FDA) to treat SMA in both infants and adults on Dec. 23, 2016, under a priority review program for rare diseases on the basis of it demonstrating statistically significant improvements in both motor function and survival.
The treatment also was given board approval, indicated to treat infantile-onset SMA, as well as patients with SMA types 1, 2 and 3.
An application for regulatory approval is under review by the European Medicines Agency (EMA), a necessary step in possibly bringing the treatment to European Union countries. Biogen also initiated a global expanded access program (EAP) in Europe for eligible patients in infantile-onset SMA (most likely to develop Type 1) in September 2016.
Biogen and Ionis Pharmaceuticals achieved several key developmental goals for the therapy. Both U.S. and European regulatory agencies have designated nusinersen an Orphan Drug for the treatment of patients with spinal muscular atrophy (SMA). The FDA also awarded nusinersen Fast Track Status for approval and Accelerated Assessment in the EU.2,3
Clinical trials and their results
The Phase 3 clinical trial known as ENDEAR (NCT02193074) was a randomized, double-blind, sham-procedure controlled, 13-month study in 121 infants diagnosed with SMA, evaluating the efficacy and safety of a 12 mg dose of Spinraza. An interim analysis found that treated infants experienced a statistically significant improvement in motor milestones compared to those not treated (40% versus 0%), as assessed by the Hammersmith Infant Neurological Examination (HINE). A smaller percentage of Spinraza-treated infant died (23%) compared to those in the untreated group (43%).
Based on the positive results of the interim analysis, the ENDEAR study was stopped and participants transitioned into the SHINE (NCT02594124) open-label study, where all patients receive Spinraza. This study is expected to conclude in February 2020.
The treatment demonstrated an acceptable safety profile in the ENDEAR trial, with respiratory events and constipation being the most commonly reported adverse events. These adverse events are consistent with those expected in infants with SMA.
Spinraza is also being evaluated in these clinical studies:
- The CHERISH trial (NCT02292537), a Phase 3 randomized, 15-month study in 126 children, non-ambulatory with later-onset SMA, between the ages of 2 and 12 years old. It is expected to finish in the summer 2017.
- The EMBRACE trial (NCT02462759) is a Phase 2 double-blind study evaluating Spinraza’s safety and pharmacokinetics in patients who didn’t meet the age and other criteria of ENDEAR and CHERISH. It’s likely completion date is April 2019.
- NURTURE (NCT02386553) is a Phase 2 trial assessing about 25 genetically diagnosed but pre-symptomatic infants, up to six weeks old when given their first dose, to determine if early treatment might prevent or delay the onset of SMA symptoms. It is set to conclude in September 2019.
More about Spinraza
Spinraza is administered by intrathecal injection, so that it is delivered directly to the cerebrospinal fluid (CSF) around the spinal cord, where motor neurons degenerate in SMA patients due to insufficient levels of SMN protein. Because it is administered intrathecally, treatment must be done in hospitals or centers whose staff are trained in performing lumbar punctures.