The FDA approved Biogen and Ionis Pharmaceuticals' nusinersen for spinal muscular atrophy (SMA) in December 2016.

SMA is a hereditary muscle-wasting disease caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Nusinersen is an antisense oligonucleotide that modulates the splicing of the related SMN2 gene. By increasing the inclusion of exon 7 into SMN2 mRNA, the drug drives production of a compensatory protein.

Interim results from a phase III trial of 121 patients showed that 40% of nusinersen-treated patients made motor milestone improvements, compared with 0% in the control patients. Data released after the approval show that the drug also reduces the risk of death or permanent ventilation: 39% of nusinersen-treated patients died or required permanent ventilation during the study, versus 68% of control patients.

The landmark drug carries a landmark cost: US$750,000 for the first year and $375,000 per year thereafter.

The FDA has approved one other splice-modulating drug, Sarepta's eteplirsen for Duchenne muscular dystrophy. This was a controversial approval that was based on data from an inconclusive 12-patient study.

Splice-modulating drugs could have utility in various other indications (Nat. Rev. Drug Discov., published online 22 July 2016).