Background: Nusinersen has demonstrated clinically meaningful efficacy in presymptomatic and symptomatic infants/children with SMA.
Objectives: Report longer-term outcomes for 5 adolescents with symptomatic SMA Type II/III treated with nusinersen who participated in SHINE (NCT02594124).
Approach: 5 teenagers age 14–15 y initiated nusinersen in CS2, received intrathecal nusinersen 12mg in CS12 extension, transitioned to SHINE long-term extension, and were 19–21 y as of 15 October 2018. Assessments included: HFMSE, WHO Motor Milestones (all); ULM (non-ambulatory); 6MWT (ambulatory); Assessment of Caregiver Experience with Neuromuscular Disease (ACEND; caregivers), and safety.
Results: Participant 1 had SMA Type II; 4 others had SMA Type III. At CS2 baseline, Participants 2–4 were ambulatory, Participants 1 and 5 non-ambulatory. From CS2 baseline to SHINE last visit (median time:1952; range:1860–2121 d), HFMSE scores changed by +5 (Participant 1), +4 (Participant 2), −3 (Participant 3), 0 (Participant 4), and −2 (Participant 5) pts. ULM scores were stable in Participants 1, 2, and 5 (0-pt change) and 6MWT distance increased in Participants 2 (+69 m), 3 (+81 m), and 4 (+24 m). Participants 2–4 maintained the ability to walk independently in SHINE. Participant 5 walked with assistance at screening and stood with assistance throughout SHINE. Participant 1 sat without support throughout SHINE. Most caregivers reported stable/improved ACEND scores in all 7 domains. The most common AEs were related to lumbar puncture or consistent with SMA disease. 1 participant had a serious AE (post-LP headache) that resolved with treatment.
Conclusions: Adolescents with SMA Type II/III treated with nusinersen showed stable/improved motor function and stable/reduced impact on caregivers over >4 years, in contrast to the expected decline based on natural history. Nusinersen safety profile was consistent with previous experience.
Study Support: Biogen; encore submission; previously presented