Spinraza (nusinersen) improves motor skills in a broad range of children with spinal muscular atrophy (SMA) type 1, including those in more advanced disease stages, according to a study of patients in Germany taking part in an Expanded Access Program (EAP) for the treatment offered by its developer, Biogen.
Spinraza is the only approved treatment for SMA — covering all or most all types — in countries that include the U.S., the European Union, Australia, Canada and South Korea (although it is not necessarily available on all national health plans). It works by increasing levels of the survival motor neuron protein, the missing protein in SMA.
The treatment’s approval was based on consistently positive results in several clinical trials, including the ENDEAR study (NCT02193074) that enrolled infants and children with infantile-onset SMA, and likely to develop type 1. ENDEAR showed that Spinraza significantly improved patients’ motor and respiratory function, compared to placebo.
Prior to Spinraza’s approval, Biogen sponsored one of the largest Expanded Access Programs yet offered for a potential rare disease treatment in 2016, a response to the urgent need for treatment in babies and children with SMA type 1 – the most severe type of SMA.
The program offered free access to Spinraza for type 1 patients of different ages and disease stages, a point that differed from the inclusion criteria of the earlier clinical trials. In Europe, more than 350 eligible children in 17 countries started and maintained Spinraza treatment.
Researchers evaluated its clinical benefits in 61 of those children after six months of treatment at seven neuromuscular centers in Germany.
Motor function was assessed through the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) — which evaluates the severely limited repertoire of motor skills in SMA type 1 infants — and motor milestones under section 2 of the Hammersmith Infant Neurological Examination (HINE).
Changes in respiratory and nutritional status were also assessed, as well as parents’ impression of motor and respiratory improvements.
Children’s mean age at symptom onset was 2.78 months, and 21 months when starting with Spinraza. Prior to treatment, a majority needed both respiratory support (35 patients or 57.4%) and some type of feeding tube for nutrition (34 or 55.7%).
After six months of treatment, motor abilities improved in 47 children (77%) as confirmed by a more than four-point increase in the CHOP INTEND score. Children on respiratory support at treatment start showed lesser motor function gains.
Older children also had lesser increases in motor function scores than younger ones, suggesting treatment response is strongly associated with age at treatment start, the study noted.
Nineteen patients (31.1%) showed improvements in HINE motor milestones, with four children (6.6%) achieving full head control and two (3.3%) being able to sit independently.
“Further research is needed to evaluate the impact of changes in CHOP INTEND score on daily life and on quality of life in children with SMA type 1, which are not as obvious as changes in motor milestones,” the researchers wrote.
No major improvements in respiratory function and nutrition were found with Spinraza treatment in this study.
Still, parents were overwhelming positive — their impressions had 93.4% of these children showing improvement in motor function after six months.
Among reported adverse events, 54.7% were classified as serious, with respiratory tract infections as the most frequent (58.5%).
Although not a randomized controlled trial, the researchers believe these results show that “even in advanced stages of the disease, nusinersen can lead to improvement of motor function as measured by CHOP INTEND,” they wrote.