Motor Milestone Achievement and Maintenance in Infants and Children Treated With Nusinersen: Data From the SHINE Study

Topic:

Gene targeted therapies

Poster Number: 77

Author(s):

Diana Castro, MD, Eugenio Mercuri, MD, Richard Finkel, MD, Basil Darras, MD, Michelle A. Farrar, Jacqueline Montes, PT, EdD, NCS, Giulia Gambino, Richard Foster, Ishir Bhan, Daniela Ramirez-Schrempp, Janice Wong, MD, MS, Wildon Farwell, MD, MPH

Institutions:

1. UT Southwestern Medical Center Dallas, 2. Department of Paediatric Neurology,Catholic University, Rome , 3. Nemours Children’s Hospital, University of Central Florida College of Medicine, 4. Boston Children's Hospital, 5. Sydney Children’s Hospital and UNSW Sydney, 6. Columbia University Irving Medical Center, 7. Biogen, 8. Biogen, 9. Biogen, 10. Biogen, 11. Biogen, 12. Biogen

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