Nusinersen is an antisense oligonucleotide approved for treating patients with spinal muscular atrophy (SMA).¹ Extensive studies such as the CHERISH study and the ENDEAR study had demonstrated nusinersen’s efficacy and tolerability in children, and several prospective real-world studies also substantiated the use of nusinersen in patients aged ≥15 years.¹ In the AAN 2023, Dr. Chad Heatwole from the University of Rochester Medical Center, the United States (US), presented the 14-month interim results of a recent study assessing the safety and effectiveness of 30-month nusinersen treatment in adult patients with type II/III SMA.¹

The SAS trial is an ongoing, multicenter, longitudinal observational study designed to evaluate the safety and effectiveness of nusinersen among adult type II/III SMA patients over 30 months of treatment.¹ Since October 2018, a total of 43 treatment-naïve adult patients aged 18-70 years were enrolled and were categorized into 2 study groups.¹ Group 1 consisted of ambulatory and non-ambulatory patients with a Revised Upper Limb Module (RULM) score ranging from 4 to 34, while Group 2 comprised ambulatory patients capable of walking independently for at least 10 meters without assistance.¹ Majority of patients (90.7%) had 3-4 SMN2 copies.¹ Primary outcome was changes from the baseline in RULM and 6-minute walk distance (6MWD).¹ Incidence of adverse events (AEs), changes from the baseline in biomarkers, pulmonary function tests, SMA-Health Index (SMA-HI) scores, and revised hammersmith scale, which assesses motor function over the entire body, were also recorded and evaluated.¹

Results from the month 14 assessment showed sustained RULM improvement from baseline among Group 1 patients (mean change: 1.0 ± 2.4, p=0.02).¹ Group 2 participants also attained a numerical but insignificant increase in 6MWD by 11.9 meters from baseline at month 14 (mean change: 11.9 ± 58, p=0.3).¹  As for changes in the revised Hammersmith scale,  a numerical improvement of 0.9 points was observed at month 14 (mean change: 0.9 ± 4.1, p=0.1).¹  Specifically, ≥30 meters increase in 6MWD from baseline, ≥2 points increase in RULM, and  ≥3 points increase in the revised hammersmith scale, regarded as minimal clinically important differences, were achieved in 45.5%, 39.1%, and 25.8% of patients treated with nusinersen for 14 months.¹

In addition, robust improvements in total SMA-HI scores were achieved at month 14 (mean change: -6.2 ± 17.3, p=0.002).¹ Pulmonary functions were stabilized during the 14-month period with a minimal change in forced vital capacity percent predicted from baseline (mean change: -0.1 ± 8.6, p=0.7).¹

In terms of safety, common AEs with nusinersen included headaches (33%), pain in the extremity (12%), upper respiratory tract infections (12%), fever (9%), and urinary tract infections (9%).¹ While 11 serious AEs occurred during the study period, none of them were related to nusinersen treatment, and all of them were resolved.¹ For laboratory abnormalities, elevated urine protein levels (≥20mg/dL) were found in 23% of patients.¹ Until the data cutoff date (30 March 2023), no deaths or treatment discontinuation due to serious AEs or laboratory abnormalities were recorded.¹

In summary, nusinersen provides an improvement in RULM and 6MWD in adult type II/III SMA patients over 14 months of treatment.¹ The interim results also indicated nusinersen’s acceptable safety profile, with generally mild-to-moderate AEs and no treatment-related serious AEs.¹ The SAS trial is still ongoing.