Background: Nusinersen’s clinically meaningful efficacy on motor function has been established across SMA populations.
Objectives: To analyze motor milestone achievement and maintenance data in infants/children who transitioned to SHINE from ENDEAR (infantile-onset) and CHERISH (later-onset SMA).
Approach: SHINE (NCT02594124) is an open-label extension for participants in previous nusinersen studies. Following a protocol amendment all participants are receiving 12 mg nusinersen every 4 months. Baseline was defined as: before initiation of the assigned treatment in ENDEAR and CHERISH; and before initiation of nusinersen in SHINE (for the previous sham-procedure group who received nusinersen in SHINE).
Results: 89 participants from ENDEAR and 125 from CHERISH transitioned. Mean (SD) total HINE-2 score at baseline was 1.5 (1.29) in those who received sham-procedure in ENDEAR (n=41), 1.4 (1.28) in those who received nusinersen in SHINE only (sham-procedure in ENDEAR; n=24), and 1.3 (1.08) in those who received nusinersen in ENDEAR and SHINE (n=81). Mean (SD) WHO motor milestone score at baseline was 1.5 (1.02) in those who received sham-procedure in CHERISH (n=42), 1.4 (1.11) in those who received nusinersen in SHINE only (sham-procedure in CHERISH; n=42), and 1.4 (0.96) in those who received nusinersen in CHERISH and SHINE (n=84). A total WHO motor milestone score at baseline of 1 was observed in 29 (69%) participants who received sham-procedure in CHERISH, 36 (86%) who received nusinersen in SHINE, and 66 (79%) who received nusinersen in CHERISH and SHINE; 1 (2%), 3 (7%), and 5 (6%) participants, respectively, had a total WHO motor milestone score of 4 at baseline. Analyses of motor milestone data over time from the SHINE 15 October 2018 data cut will be presented.
Conclusions: Continued data analysis from the SHINE study will increase the information available on the long-term effects on motor milestones of repeated nusinersen doses.
Support: Biogen; encore submission