Ambulatory SMA patients on Spinraza show walking gains
Meaningful changes among type 3 and 4 children, adults in real-world study
More than 1 in 4 ambulatory spinal muscular atrophy (SMA) patients experienced clinically meaningful improvements in walking ability after being treated with Spinraza (nusinersen), according to an analysis of real-world findings in Europe.
“Our data demonstrate a positive effect of [Spinraza] treatment on motor function in ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance in a subgroup of patients,” the researchers wrote.
Many patients also reported a marked reduction in fatigue with Spinraza’s use.
“Our results contribute to the increasing evidence on the positive long-term effect of nusinersen treatment in this patient population. This is necessary to develop treatment recommendations, but also to facilitate and guarantee access to treatment,” Astrid Pechmann, MD, a study co-author at the University of Freiburg in Germany, said in a university press release.
Focus on milder SMA forms to help ensure patient access to Spinraza
The study, “Improvements in Walking Distance during Nusinersen Treatment – A Prospective 3-year SMArtCARE Registry Study,” was published in the Journal of Neuromuscular Diseases.
Spinraza was the first disease-modifying treatment for SMA to become widely available. Sold by Biogen, the therapy works to boost levels of the SMN protein, whose deficit causes SMA.
Approvals of Spinraza were supported mainly by data from clinical trials that tested the therapy in children with SMA types 1 or 2. In the absence of treatment, patients with these severe SMA types are not expected to ever walk independently.
Its effectiveness for those with relatively milder SMA types 3 and 4 is less well studied. These patients are typically able to walk as children, though they can lose that ability as the disease progresses, especially in comparatively more severe cases of type 3 disease.
“Data on the long-term effect of [Spinraza] in ambulant patients are still scarce. Due to reimbursement policies, this led to limited access to treatment for adult or ambulant patients in different countries,” Pechmann said.
An international team of scientists investigated outcomes for 231 people with SMA who were treated with Spinraza. All were able to walk when they started on the therapy.
The researchers stressed that, because they focused only on ambulatory patients and excluded those with type 3 but not ambulatory, their study “does not represent the whole spectrum” of milder SMA.
Data were obtained from SMArtCARE, a registry that collects information on SMA patients treated at dozens of European centers, including those across Germany, Austria, and Switzerland. The SMArtCARE registry is funded in part by Biogen and Novartis Gene Therapies, which markets the SMA gene therapy Zolgensma.
Among the 231 patients, 114 were children and the other 117 were adults when they started treatment. Ambulatory adults with SMA tended to have an older age at disease onset (about 11.5 years vs. 3.4 years for ambulatory children), which was expected as patients with an earlier age at onset are more likely to lose walking ability at a younger age.
Patients were followed for up to 38 months (more than three years), though data was not available for all measures at every time point in the real-world database. The fact that the study relied on real-world findings, which are messier and less well-controlled than data from clinical trials, was noted as both a strength and a limitation of the analysis.
To assess walking ability, researchers looked at scores on the six-minute walk test (6MWT), a common assessment that simply measures how far a patient can walk in six minutes. A change of at least 30 meters (nearly 100 feet) in 6MWT scores is considered clinically meaningful.
Meaningful 6-minute walking distance gains for one-quarter of patients
Over the total observation period, more than a quarter of Spinraza-treated patients — 31 (27.2%) children and 31 (26.5%) adults — experienced a clinically meaningful improvement of greater than 30 meters on the 6MWT. The average change from the start of treatment to month 38 was 39.3  meters in children and 24.4 meters in adults.
By comparison, five adults (4.3%) experienced a decrease of 30 meters or more in walking ability while on Spinraza, and two children (1.8%) lost the ability to walk without assistance while being treated.
Average scores on other measures of motor function — specifically the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) — generally improved among pediatric patients and were stable for adults on Spinraza.
About a third of the patients (33.3% of children and 35.9% of adults) experienced a clinically meaningful improvement on the HFMSE, while 9.4% of adults showed a clinically significant worsening of HFMSE scores. For RULM, clinically meaningful improvements were seen in 23.7% of children and 14.5% of adults, while clinically significant worsening was reported in 2.6% of adults.
Respiratory function remained stable throughout the study, with three adults requiring non-invasive ventilatory support during the observation. One pediatric patient also required a feeding tube for six months.
Before starting on treatment, about 1 in 3 patients (29.9%) reported clinically significant fatigue. After some three years on Spinraza, the number reporting fatigue had dropped to less than 1 in 10 (9.1%).
“Both pediatric and adult patients reported a remarkable reduction of perceived fatigue after 38 months of treatment,” the researchers wrote.
Side effects were observed in 40 (17.3%) of these patients over the study’s three years. The most common were complications related to the spinal canal injection, fractures and accidents, and infections.
“Our results demonstrate a stabilization of disease progression and, more importantly, clinically meaningful improvements in walking distance in both pediatric and adult SMA patients,” the researchers wrote.
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