Background: Nusinersen clinical trial results have shown significant and clinically meaningful efficacy across SMA subtypes. A previous integrated safety analysis of five nusinersen trials in later-onset SMA showed a favorable benefit–risk profile over a median of 1.2 (range: 0.08–4.2) years.
Objectives: To evaluate the longer-term safety of nusinersen by total and annual incidence of serious adverse events (SAEs) in participants with later-onset SMA who had their first dose of nusinersen in CS1, CS2, CHERISH, EMBRACE Parts 1/2, or SHINE and included any follow-up in CS2, CS10, CS12, EMBRACE Part 2, and SHINE extension. Safety results are reported from nusinersen initiation through the 27 August 2019 SHINE data cut.
Results: SAEs were documented in 39% (74/190) of participants over a median of 4.0 (range: 0.08-7.6) years of follow up. No SAEs were considered by the investigator to be related to study drug (does not include events considered possibly related). Two deaths were reported (1 acute respiratory distress, 1 acute respiratory failure). The incidence of SAEs in ?3 participants by MedDRA Preferred Term were: pneumonia in 8%; gastroenteritis, pneumonia viral, respiratory syncytial virus infection in 3% each; bronchitis in 2%; gastroenteritis viral, rhinovirus infection in 2% each; scoliosis in 9%; foot deformity, kyphoscoliosis in 2% each, respiratory distress in 4%; acute respiratory failure in 3%; and post-lumbar puncture syndrome in 5%. The annualized incidence of SAEs in participants with 4 years of follow-up (N=97) was 10%, 5%, 6%, and 9% in Years 1 through 4, respectively, with serious post–lumbar puncture syndrome in 1 (1%) participant in Years 1 and 2 each and none in Years 3 and 4.
Conclusions: The most common SAEs in participants with later-onset SMA were consistent with the disease itself or the lumbar puncture procedure and there were no new or concerning trends identified over 4 years of treatment with nusinersen.
Study Support: Biogen