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Neuromuscul Disord. 2019 Nov;29(11):842-856. doi: 10.1016/j.nmd.2019.09.007. Epub 2019 Sep 12.

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.

Author information

1
Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: dcd1@cumc.columbia.edu.
2
Unit of Neuromuscular and Neurodegenerative Disorders, Post-Graduate Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy.
3
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
4
Departments of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
5
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6
Division of Neurology, Department of Pediatrics, Nemours Children's Hospital, Orlando, FL, USA.
7
Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Neuropediatrics, University Medical Hospital, Bonn, Germany.
8
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
9
Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
10
Royal Children's Hospital, University of Melbourne, Murdoch Children's Research Institute, Melbourne, Australia.
11
Department of Pediatrics and Neurology, University of Utah, Salt Lake City, UT, USA.
12
Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.
13
Sidra Medicine, Department of Pediatrics, Qatar Foundation, Doha, Qatar; Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
14
NEMO Clinical Center - NEuroMuscular Omniservice, Milan, Italy; Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
15
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University; Departments of Pediatrics and Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
16
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
17
Biogen, Cambridge, MA, USA.
18
Biogen, Maidenhead, Berkshire, UK.

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.

KEYWORDS:

Clinical trial; Neurofilament; Newborn screening; Nusinersen; Presymptomatic; Spinal muscular atrophy

PMID:
31704158
DOI:
10.1016/j.nmd.2019.09.007
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