Longer-term Experience with Nusinersen in Teenagers and Young Adults with Spinal Muscular Atrophy: Results from the CS2/CS12 and SHINE Studies
John W. Day1, Kathryn J. Swoboda2, Basil T. Darras3, Claudia A. Chiriboga4, Susan T. Iannaccone5, Darryl C. De Vivo4, Nicholas Deconinck6, Richard S. Finkel7, Mar Tulinius8, Kayoko Saito9, Jacqueline Montes4, Peng Sun10, Ishir Bhan10, Boris Kandinov10, Janice Wong10, Wildon Farwell10
1Stanford University School of Medicine, 2Massachusetts General Hospital, 3Boston Children's Hospital and Harvard Medical School, 4Columbia University Irving Medical Center, 5University of Texas Southwestern Medical Center, 6Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 7Nemours Children's Hospital, 8University of Gothenburg, 9Tokyo Women’s Medical University, 10Biogen
Objective:
To report longer-term outcomes for five adolescents with symptomatic SMA Type II/III treated with nusinersen who participated in SHINE (NCT02594124).
Background:
Nusinersen has demonstrated clinically meaningful efficacy in presymptomatic and symptomatic infants/children with SMA.
Design/Methods:
Five teenagers aged 14–15 years initiated nusinersen in CS2 (Phase 1b/2a), received intrathecal nusinersen 12mg in CS12 extension, transitioned to SHINE long-term extension, and were 19–21 years as of 15 October 2018. Assessments included: HFMSE, WHO Motor Milestones (all participants); ULM (non-ambulatory); 6MWT (ambulatory); Assessment of Caregiver Experience with Neuromuscular Disease (ACEND; caregivers), and safety.
Results:
Participant 1 had SMA Type II; all 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] days), HFMSE scores changed by +5 (Participant 1), +4 (Participant 2), −3 (Participant 3), 0 (Participant 4), and −2 (Participant 5) points. ULM scores were stable in Participants 1, 2, and 5 (0-point change) and 6MWT distance increased in Participants 2 (+69 m), 3 (+81 m), and 4 (+24 m). During SHINE, Participants 2–4 maintained the ability to walk independently. 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. One participant had a serious AE (post-lumbar puncture headache) that resolved with treatment. New 2019 interim analysis data will be reported.
Conclusions:

Teenagers with SMA Type II/III treated with nusinersen demonstrated stable/improved motor function and stable/reduced impact on caregivers over >4 years, in contrast to the expected slow decline based on SMA natural history. Nusinersen safety profile was consistent with previous experience.

Study Supported by: Biogen