Nusinersen is an antisense oligonucleotide for children with later-onset spinal muscular atrophy.
Data from a phase 3 end of study of nusinersen (Spinraza) demonstrated significant improvement in motor function among children with later-onset spinal muscular atrophy (SMA).
Nusinersen is an antisense oligonucleotide designed to treat SMA by altering the splicing of SMN2 pre-mRNA to increase the production of full-length SMN protein. It is administered via intrathecal injections, according to a press release.
The multicenter, randomized, double-blind, sham-procedure controlled, phase 3 CHERISH study was designed to assess the safety and efficacy of nusinersen in children with later-onset SMA.
Nusinersen was investigated in 126 non-ambulatory children aged 2 to 12 years who experienced symptom onset at greater than 6 months of age, according to the study.
The results of the 15-month study showed that children administered nusinersen experienced a highly statistically significant and clinically meaningful improvement in motor function compared with untreated children.
When changes were measured from baseline, children who received nusinersen achieved a 3.9-point mean improvement at month 15, whereas children who did not receive nusinersen experienced a mean decline of 1.0 point.
The primary endpoint results of the analysis were consistent with results observed at the interim analysis, according to the press release.
Additional endpoints that included attainment of new motor milestones and upper limb motor function were consistently in favor of children who received nusinersen. Overall, nusinersen demonstrated a favorable safety profile, according to the press release.
Treatment-emergent adverse events (AEs), severe AEs, and serious AEs (SAEs) were reported less frequently in children administered nusinersen compared with those who did not receive treatment.
Most of the AEs were considered related to SMA, were common events in the general population, or were related to the lumbar puncture procedure. None of the study participants discontinued treatment due to AEs.
“In CHERISH, most children with later-onset SMA treated with Spinraza saw improvements in motor function and stabilization or slowing of disease progression,” Dr Richard Finkel, chief of neurology, Nemours Children's Hospital, said in a press release. “As a physician who has spent 37 years treating children with SMA, it’s incredibly encouraging to see some patients on Spinraza achieve milestones such as crawling and standing with assistance within the clinical trial. These kinds of clinically meaningful improvements are unprecedented and give new hope to individuals with SMA and their families.”
Data from the end of study will be presented at the American Academy of Neurology annual meeting in Boston, MA. Additionally, Biogen will also present new interim data from the phase 2 NURTURE study.
“The CHERISH study, conducted in collaboration with Ionis, further demonstrates the meaningful impact SPINRAZA can have in children with later-onset SMA, and reaffirms the benefit of treatment across SMA populations,” Alfred Sandrock, MD, PhD, executive vice president and chief medical officer at Biogen, said in a release. “Our clinical development program demonstrates the impact of early treatment, which is confirmed by NURTURE data showing significant motor milestone improvements generally consistent with normal development in presymptomatic infants treated with Spinraza.”
NURTURE is a multicenter, open-label, single-arm phase 2 study examining nusinersen for the treatment of infants younger than 6-weeks-old with genetically diagnosed SMA who were presymptomatic at treatment initiation.
At the time of the interim analysis, infants were enrolled for a median of 317.5 days. All infants were alive and none required respirator intervention, such as chronic noninvasive ventilation, invasive ventilation, or tracheostomy.
Most infants achieved motor milestone and growth parameter gains that were generally consistent with normal development, such as head control, independent sitting, and standing and/or walking independently, according to the release.
According to the investigators, treatment-emergent AEs were possibly related to nusinersen, but all were resolved. None of the infants discontinued treatment or withdrew from the study due to AEs. There were no new safety concerns identified, according to the release.
“The results from NURTURE are significant, as they continue to demonstrate the importance of beginning Spinraza treatment as soon as possible after an SMA diagnosis and the major impact that early treatment may have across a broad range of SMA populations,” Sandrock, MD, PhD, said.