Evrysdi treatment safe, effective in adults with SMA: Real-world study
Patients also reported improvements in fatigue, quality of life
Treatment with Evrysdi (risdiplam) is generally safe and effective at improving or stabilizing motor and lung function in adults with spinal muscular atrophy (SMA) for up to two years, according to a real-world study in Belgium.
Results also suggested easing of difficulty swallowing and fatigue, as well as improved patient-reported quality of life.
“This study contributes to the evidence supporting the effectiveness and safety of Risdiplam [Evrysdi] treatment in adult SMA patients,” researchers wrote.
The study, “Two-year Risdiplam treatment in adults with spinal muscular atrophy: improvements in motor and respiratory function, quality of life and fatigue,” was published in Neuromuscular Disorders. The study was funded by Roche, which co-markets Evrysdi with subsidiary Genentech.
Treatment with Evrysdi improved SMA patients’ motor function
SMA is mainly caused by mutations in the SMN1 gene that result in a deficiency of the survival motor neuron protein (SMN), which is important for the survival and function of motor neurons — the nerve cells that control voluntary movements. This results in the progressive loss of these neurons, and the development of symptoms like muscle weakness and wasting.
Evrysdi is a disease-modifying treatment that works to increase the levels of SMN protein produced by the SMN2 gene, a backup gene of SMN1 that normally produces only a small percentage of functional SMN protein. The treatment is approved to treat children and adults with all types of SMA, “however, long-term efficacy and safety data in adult SMA patients are limited,” the researchers wrote.
In this study, researchers analyzed Evrysdi’s safety and efficacy in 18 adults with SMA who were treated for 24 months, or two years, at the University Hospitals Leuven in Belgium. Participants were mainly women (61%) who had a mean age of 38.6 years and a mean disease duration of 34.1 years.
Overall, half of the participants had SMA type 3, 44% had SMA type 2, and 6% had SMA type 4. The majority (89%) was not able to walk, almost all had scoliosis – a sideways curvature of the spine due to weakness in back muscles – and 71% underwent surgery for scoliosis. They had not been previously treated with Spinraza (nusinersen).
These findings suggest that, despite treatment, disease progression may still occur in some individuals, potentially due to individual variability in disease course or treatment response.
Treatment with Evrysdi significantly improved the participants’ motor function, demonstrated by an increase in the Motor Function Measure-32 (MFM-32) of 2.3% after one year and 2.6% after two years. Participants also experienced a significant improvement in upper limb motor function after one year, according to the disease-specific Revised Upper Limb Module (RULM).
After two years, 47% of the participants experienced a clinically significant improvement in the MFM-32 score (an increase of at least three points) and 29% experienced a meaningful improvement in RULM (an increase of at least two points). In contrast, one patient exhibited clinical worsening in MFM-32 and two in RULM after two years.
“These findings suggest that, despite treatment, disease progression may still occur in some individuals, potentially due to individual variability in disease course or treatment response,” the researchers wrote.
Patient-reported outcomes showed gains in general health
In terms of pulmonary function, the peak expiratory flow (PEF) — a measure of the speed of exhaled air — significantly increased by 6.9% after two years. Forced vital capacity (FVC), or the maximum amount of air a person can forcibly exhale after a deep breath, did not change significantly overall, as some patients improved while others deteriorated.
In the five years before beginning treatment, the patients’ FVC was declining by 1.3% per year, while PEF deteriorated by 0.2% per year.
According to the researchers, “these results showed the possible stabilizing effect of [Evrysdi] on the respiratory function in this patient population.”
Patients with SMA type 3 had significantly higher FVC and PEF than those with SMA type 2.
Additionally, patient-reported outcomes after two years of treatment indicated significant improvements in subdomain of a quality of life questionnaire — general health improved by 8.8% and health change by 17.6%. Patients also reported a significant decrease in fatigue and easier swallowing.
“Together, these findings highlight the subjective, but meaningful, improvement of health due to [Evrysdi] treatment,” the researchers wrote.
During the study, the most frequent adverse event related to therapy was abdominal pain, which was seen in two patients within the first week after starting treatment. One patient died due to aspiration pneumonia, which was considered unrelated to the treatment.
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