Nusinersen in Teenagers and Young Adults with Spinal Muscular Atrophy: Longer-term Experience Based on Results from the CS2/CS12 and SHINE Studies


Gene targeted therapies

Poster Number: 41


John Day, MD, PhD, Kathryn J. Swoboda, Basil Darras, MD, Claudia A. Chiriboga, Susan T. Iannaccone, MD, Darryl C. De Vivo, MD, Nicolas Deconinck, Richard Finkel, MD, Mar Tulinius, Kayoko Saito, Jacqueline Montes, PT, EdD, NCS, Laurence Mignon, Peng Sun, Ishir Bhan, Sarah Gheuens, Daniela Ramirez-Schrempp, Sandra P. Reyna, Janice Wong, MD, MS, Wildon Farwell, MD, MPH


1. Stanford, 2. Massachusetts General Hospital, 3. Boston Children's Hospital, 4. Columbia University Irving Medical Center, 5. University of Texas Southwestern Medical Center, 6. Columbia University Irving Medical Center, 7. UZ Gent and Hôpital Universitaire des Enfants, Université Libre de Bruxelles, Brussels, Belgium, 8. Nemours Children’s Hospital, University of Central Florida College of Medicine, 9. University of Gothenburg, 10. Tokyo Women’s Medical University, 11. Columbia University Irving Medical Center, 12. Ionis Pharmaceuticals, Inc., 13. Biogen, 14. Biogen, 15. Biogen, 16. Biogen, 17. Biogen, 18. Biogen, 19. Biogen

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