Nusinersen linked to improved motor function in spinal muscular atrophy

Key takeaways:

• Interim results also showed reduction of the neurodegenerative biomarker neurofilament light chain.
• Serious adverse events occurred in 13 of 38 patients in the safety cohort, none directly related to nusinersen.

Treatment with nusinersen was linked to increased motor function and reduction of the neurodegenerative biomarker neurofilament light chain in children with spinal muscular atrophy, according to interim results of a study.

“The phase 4 RESPOND study evaluates clinical outcomes and safety following treatment with nusinersen (Spinraza) over a 2-year period in infants and toddlers with spinal muscular atrophy who have unmet clinical needs,” Crystal Proud, MD, pediatric neurologist at Children’s Hospital of the King’s Daughters in Virginia, told Healio in an email.

Proud presented the research in a poster at the 2024 Muscular Dystrophy Association Clinical & Scientific Conference.

The researchers sought to examine whether administration of nusinersen increases motor neuron protein production in motor neurons, as well as if it is safe and well-tolerated in children with spinal muscular atrophy who have already been treated with Zolgensma, a gene therapy targeted for those with the condition.

In RESPOND, a single-arm, multicenter, open-label clinical trial, analysis centered on baseline characteristics and interim clinical, neurofilament light chain outcomes and safety findings.

The study included an interim population (n = 29) of children who received at least one dose of nusinersen and who had the opportunity to complete the 183-day assessment as of the data cut in November 2022, along with a safety set (n = 38) that included all children who received at least one dose of the drug.

Primary outcome for the interim data set was total Hammersmith Infant Neurological Examination (HINE-2) score as well as presence of plasma neurofilament light chain (NfL), while primary outcomes for the safety set was safety and tolerability of nusinersen.

According to results, at day 183, participants with suboptimal motor function at baseline reported improvement (92% in G1, 91% in G2). There was some improvement reported in suboptimal swallowing/feeding ability or respiratory function, but most often no change.

Data further showed that mean change from baseline to day 183 in total HINE-2 score was 5.4 in G1 and 5.2 in G2, with mean scores reaching 8.6 and 13.5 in each group, respectively.

Researchers additionally found that reductions in NfL levels occurred after nusinersen treatment, indicating a slowing of axonal injury and neurodegeneration.

Adverse events occurred in 31 of 38 (82%) patients, with the most common being infections/infestations (63%) and respiratory, thoracic and mediastinal disorders (26%). Two patients (5%) had an adverse event determined to be drug-related (mild proteinuria), which resolved, while 13 patients had serious adverse events, none related to nusinersen itself.

“Improvements in motor function together with decreases in neurofilament levels seen after treatment with nusinersen (Spinraza) in RESPOND show that we may be able to further optimize benefits for patients,” Proud told Healio.