Commencing Novel Therapies for Adult Sma Patients: Experience from a Hybrid Clinic

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that affect both adults and children. Two novel therapies were approved for patients in England by NICE (Nusinersen via Management Access Agreement (MAA) and Risdiplam via Early Access to Medicine scheme (EAMS)). Setting up baseline assessments, designing new pathways, acquiring personnel and resources have been challenging. We present a pathway analysis of the new clinic set-up, process of patient choice, risk minimisation in intro- ducing the two novel therapies, and the impact therapies have had on adult cohort of SMA patients. Total of 58 patients included (31 had type 2 SMA and 27 had type 3[only 11/27 were ambulant]. The average age of patients with type 2 and 3 SMA was 25 and 33 respectively. 19 patients chose risdiplam (oral) and 22 are on nusinersen (intra thecal). We analysed factors that govern patients' treatment decisions. We report factors that helped early success in our hybrid clinic set-up. Set criteria on each scheme;but potential side effects, information availability, route of administration (mainly previous spinal surgery), speed at treatment initiation but not COVID directed many patients' treatment decisions. A battery of outcome measures were analysed to establish treatment impact at 12 months.

Risdiplam for the treatment of adults with spinal muscular atrophy: Experience of the Northern Ireland neuromuscular service.

INTRODUCTION/AIMS: Risdiplam is the newest available treatment for patients with spinal muscular atrophy (SMA). There is little information on its use in adults. We present the clinical experience of adults with SMA treated with risdiplam through the Early Access to Medicines Scheme (EAMS) in Northern Ireland. METHODS: All adults with Type 2 SMA attending the regional neuromuscular clinic were offered risdiplam treatment. Patients had assessments of respiratory function, the Epworth Sleepiness Scale (ESS), Quality of Life Measure for People with Slowly Progressive and Genetic Neuromuscular Disease (QOLM), and Egen Klassifikation 2 (EK2) every 3 mo and the Revised Upper Limb Module for SMA (RULM) at baseline and 6 mo. All assessments other than the RULM were carried out virtually. RESULTS: Six of seven patients who were offered risdiplam consented to treatment through the EAMS (five female, one male, mean age 33.7 y). It was generally well tolerated other than skin photosensitivity in all patients. All patients remained on therapy at 9 mo. All reported meaningful improvements in overall strength, sense of wellbeing, and speech quality. There was no change in respiratory function, daytime hypersomnolence, or upper limb function (all p > .05). There was improvement in the QOLM (p = .027) and EK2 (p = .009). DISCUSSION: Our study raises hopes that risdiplam may be efficacious in adults; however, more systematic studies in larger cohorts are needed before drawing any definitive conclusions. This study also demonstrated the feasibility of virtual assessments.

Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1.

INTRODUCTION/AIMS: There are currently three medications approved for spinal muscular atrophy (SMA), but the use of these medications in combination has not been well described. METHODS: This is a retrospective report of four cases of SMA treated with dual onasemnogene and risdiplam therapy at our institution. RESULTS: Following onasemnogene therapy, all four patients experienced a perceived plateau of therapeutic benefit, at which time daily risdiplam was started. Transient fatigue and weakness was seen in two patients following risdiplam initiation, but this resolved within 1 mo. One patient was hospitalized with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and post-viral pneumonia, weeks following risdiplam initiation. No other adverse effects related to onasemnogene and risdiplam combination therapy were identified and all patients experienced objective and subjective improvement. DISCUSSION: Combination therapy with onasemnogene and risdiplam in patients with SMA appears to be well-tolerated. Further large prospective trials are needed to determine whether dual therapy is more efficacious than monotherapy, and to identify rare adverse events that may occur with the use of combination therapy.