A prospective, multi-center, observational study of the safety, tolerability and effectiveness of Nusinersen in adult patients with spinal muscular atrophy.

Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age 37.1 (11.9) years) enrolled and completed baseline assessments. Serial assessments over 30 months showed small but not significant improvements in the six minute walk test (16.1 m), Revised Upper Limb Module (0.7), Revised Hammersmith Scale (0.8), maximal inspiratory (-2.6 cm H20) and expiratory pressure (12.3 cm H20). Muscle strength and forced vital capacity did not change. The patient reported outcome Total SMA-HI improved (-11 (95% CI: -17,-5); p < 0.001)). No new safety effects were identified. This study of nusinersen in adults with SMA demonstrates stability over time in contrast to the expected decline in untreated patients, with a favorable safety profile.