Authors' objectives: Until the advent of SMA therapies, the only treatment was best supportive care. Three treatments have been approved: Nusinersen in 2017, onasemnogene abeparvovec in 2020 and risdiplam in 2021. Nusinersen and risdiplam both work by increasing the availability of functional SMN protein in cells, with the important difference that nusinersen needs to be administered intrathecally whilst risdiplam can be taken orally. Onasemnogene abeparvovec is a viral vector-based gene therapy. The present review aims to update the evidence on longer-term safety and efficacy (≥24 months for nusinersen and onasemnogene abeparvovec and ≥12 months for risdiplam) as monotherapies or in combination with particular attention to stabilisation and persistence of motor skills, effect on respiratory and nutritional function and overall quality of life in patients with SMA 1 to 4.

Authors' results and conclusions: Twenty observational studies and one RCT were included in the synthesis, reporting on 1374 patients in total. Fifteen studies investigated nusinersen in 948 patients, one study was identified on onasmenogene abeparvovec, evaluating 12 patients and two studies investigated risdiplam in 221 patients. A combination of therapies was received by 193 patients. The results show clinically relevant improvements in motor skills in SMA type 1 patients, especially in patients with early treatment initiation and ≥2 SMN2 copies, as well as a stabilisation of health status in SMA type 2 and 3 patients. In all studies reporting these outcomes, no significant improvements in respiratory and nutritional function were reported regardless of SMA type and therapy used, with most studies reporting no change or an increase in the need for ventilation and nutritional support. Adverse events were common in all studies that reported it but seldom classified as treatment-related. Post-lumbar puncture syndrome was frequently reported across nusinersen studies and, overall, disease-related respiratory complications were common. Conclusion: The clinical data show that all therapies have an impact on the motor function, in all SMA-type patients with clear indications that early treatment initiation leads to better outcomes, showcasing the importance of newborn screening. Improvements and stabilisation in older, later-onset SMA patients were also evident. In any case there is no compelling evidence to support the notion of a "curative" therapy, but rather a "disease-modifying" treatment.

Authors' methods: A systematic literature search was conducted in July 2023. The selected publications were assessed for internal validity and risk of bias and all relevant data were extracted into standardised tables. Results were summarised narratively as the substantial heterogeneity of the studies prevents any meaningful quantitative analysis.

Project Status: Completed

URL for project: https://aihta.at/page/homepage/en

Year Published: 2023

URL for published report: https://eprints.aihta.at/1485/1/Policy_Brief_001_2nd_Update.pdf

URL for additional information: https://eprints.aihta.at/1485/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Austria

Organisation Name: Austrian Institute for Health Technology Assessment

Contact Address: Garnisongasse 7/20, A-1090 Vienna, Austria

Contact Name: office@aihta.at

Contact Email: office@aihta.at