Nusinersen Phase 2 Trial Results Published in The Lancet

15 December 2016

Results from a phase 2 clinical trial of the Ionis Pharmaceuticals gene therapy drug, Nusinersen (now marketed as Spinraza), have been published in the medical journal The Lancet.

Initiated in 2013 (click here and here for further information), this trial was an open-label study designed to assess the safety, tolerability, pharmacokinetics, and efficacy of repeated spinal cord injections of Nusinersen, an antisense oligonucleotide that targets the SMN2 “backup” gene, encouraging it to produce more survival motor neuron (SMN) protein.

Twenty patients with infantile onset (3 weeks to 6 months) type 1 SMA were divided into two treatment groups; group 1 received three doses of Nusinersen at 6 mg followed by 12 mg doses, while group 2 were given 12 mg doses throughout.

Patients receiving the 12 mg dose showed incremental achievements of motor milestones, improvements in motor function, and increased survival compared to natural history studies of SMA.

Nusinersen was shown to be taken up by motor neurons throughout the spinal cord, and other nerve cells in the brain, where it successfully increased the amount of SMN protein made by the SMN2 gene.

Unfortunately, Nusinersen did not completely reverse SMA symptoms in any participant, and not all patients showed the same level of positive response to the drug.

Nevertheless, this small-scale trial, which is a forerunner to the ENDEAR, CHERISH, NURTURE, and EMBRACE phase 2 and 3 trials, was the first to provide robust evidence that Nusinersen is safe and well tolerated, and provides encouraging evidence for its clinical effectiveness in SMA patients.

Further Information

Trial Site

Lancet publication

Commentary on the Lancet publication by Tom Gillingwater

News article on the trial