Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder that causes progressive muscle weakness and wasting, resulting in loss of motor function. The oral drug risdiplam demonstrated improvement or stabilization of motor function in clinical studies of patients with SMA. Professor Sophelia Chan of the Department of Paediatrics and Adolescent Medicine, University of Hong Kong, shared the latest published local findings on treatment outcomes with risdiplam in paediatric and adult patients with SMA.
SMA subtypes and symptoms
SMA, caused by mutations in the survival motor neuron 1 gene (SMN1), results in degeneration of motor neurons, progressive muscle weakness and loss of motor function. However, a nearly identical SMN2 gene produces a small amount of functional SMN protein, and having higher SMN2 copies is generally associated with milder phenotypes of SMA. [J Neuromuscul Dis 2020;7:1-13]
SMA is classified into four clinical subtypes based on the age of onset and motor milestones achieved. [J Neuromuscul Dis 2020;7:1-13]
Risdiplam: The only oral noninvasive treatment for SMA
Three disease-modifying treatments (DMTs) are currently approved for SMA in Hong Kong — risdiplam, nusinersen and onasemnogene abeparvovec. Risdiplam is an orally administered small molecule drug indicated for use in both adult and paediatric SMA patients. Nusinersen, an antisense oligonucleotide approved for patients with SMA, requires regular intrathecal administration every 4 months in addition to four initial loading doses. Onasemnogene abeparvovec, a gene replacement therapy approved for children <2 years of age, is given as a single intravenous dose. [Evrysdi Prescribing Information, September 2024; Drug Des Devel Ther 2022;16:1865-1883; Nusinersen US Prescribing Information]
“As an oral treatment, risdiplam provides a simple and convenient option, freeing patients from anxiety and distress associated with needles, sedation and hospital stays,” noted Chan.
HK study: Risdiplam in paediatric & adult SMA patients
The effectiveness of risdiplam in Hong Kong was evaluated in paediatric (n=10) and adult (n=24) patients with symptomatic SMA in a prospective study. The patients either received risdiplam as first-line therapy (adult, n=22; paediatric, n=3) or switched from nusinersen to risdiplam (adult, n=2; paediatric, n=7). The reasons for switching were problems related to intrathecal access or side effects. [Eur J Neurol 2026;33:e70574]
One of the paediatric patients had two SMN2 copies, and the rest had three. Almost all adult patients had either three or four SMN2 copies. The mean age at risdiplam initiation in the paediatric and adult cohorts were 11.5 and 30.2 years and the mean duration of follow-up were 3.4 and 2.7 years, respectively. Select baseline patient characteristics are summarized in the Table.
HRQoL assessments in paediatric patients
The PedsQL Family Impact Module, which has a validated Chinese version, was used to measure the impact of SMA and treatment on parents and family. These included the parents’ self-reported physical, emotional, social and cognitive well-being as well as parent-reported daily family activities and family relationships. [Eur J Neurol 2026;33:e70574]
“Sixty-seven percent of the parents [6 out of 9] reported that health-related quality of life [HRQoL] and family functioning with their child were better or maintained on risdiplam treatment, and notably, their physical well-being significantly improved after 2 years of treatment,” reported Chan.
The PedsQL 3.0 Neuromuscular Module was used to assess the child’s disease state and ability to communicate about his/her disease, as well as family resources. Scores from parallel parent proxy-report forms and child self-report forms showed that 89 percent of parents (8 out of 9) and 67 percent of children (4 out of 6) had overall improvement or maintenance in the child’s HRQoL. Parents reported significantly improved disease state of their children after 2 years of treatment, and children reported improved ability to communicate about their disease after 3 years of treatment. [Eur J Neurol 2026;33:e70574]
Other patient-/parent-proxy reported outcomes
A simple survey was conducted among the paediatric cohort (patient and parent-proxy reports) 1 year after initiation of risdiplam to assess treatment impact on physical functions. For the adult cohort, relevant information was extracted from electronic health records. [Eur J Neurol 2026;33:e70574]
“Improvements were reported in paediatric and adult motor function [paediatric, 100 percent; adult, 45.8 percent], respiratory function [50 percent; 12.5 percent], swallowing [75 percent; 12.5 percent], speaking [50 percent; 0 percent], and feelings of more invigoration [62.5 percent; 8.3 percent] or less fatigue [0 percent; 20.8 percent],” noted Chan. “Overall, the benefits of treatment were greater among the paediatric cohort.”
Motor outcomes in paediatric & adult patients
The impact of risdiplam on motor performance among paediatric and adult SMA patients was assessed using the Hammersmith Functional Motor Scale-Expanded (HFMS-E) and Revised Upper Limb Module (RULM) scales. [Muscle Nerve 2017;55:869-874; Muscle Nerve 2019;59:426-430; Pharmacotherapy 2024;44:97-105]
“The most notable improvement in the HFMS-E score within the paediatric cohort was observed in a single patient with SMA type 3,” reported Chan. “The improvement in the adult cohort was modest, but they did either improve or maintain their scores.” (Figure) [Eur J Neurol 2026;33:e70574]
“Patients with higher RULM entry item scores [≥2] remained stable or improved more as compared with those with lower entry item scores,” highlighted Chan. After 3 years of treatment, RULM scores were significantly improved in patients who received risdiplam as first therapy, but not in those who switched from nusinersen. [Eur J Neurol 2026;33:e70574]
The Adapted Test of Neuromuscular Diseases (ATEND) and the 32-item Motor Function Measure (MFM32) were also used to assess motor performance. ATEND is a wheelchair-based motor assessment for nonambulatory individuals where they are tested in semi-reclined and supported sitting positions. [Neuromuscul Disord 2022;32:S61] MFM32 is suitable for both nonambulatory and ambulatory patients, and evaluates three domains of motor function: standing and transfers, axial and proximal mobility, and distal motor mobility. [Neuromuscul Disord 2005;15:463-470]
“ATEND and MFM32 scores improved or remained stable in almost all paediatric and most adult patients,” reported Chan. Both patients who received risdiplam as first therapy and those who switched from nusinersen demonstrated significant improvements in MFM32 scores after 3 years of treatment. The motor improvements were more pronounced in the less affected distal muscle groups, especially in upper limbs, as evaluated by RULM and MFM32. (Figure) [Eur J Neurol 2026;33:e70574]
“It is important to note that motor maintenance in these patients is correlated with and contributes to HRQoL,” concluded Chan.
Safety
“Risdiplam treatment was safe with minimal side effects. One paediatric patient had skin rash, which subsequently resolved. Gastrointestinal issues were common among adults, with five patients reporting diarrhoea and one of them permanently discontinuing treatment,” noted Chan. Other side effects, including skin rash, hair loss, acne, constipation, and insomnia, were also noted in adult patients. [Eur J Neurol 2026;33:e70574]
