Nusinersen in later-onset spinal muscular atrophy
Long-term results from the phase 1/2 studies
Citation Manager Formats
Make Comment
See Comments

Article Information
- Received July 12, 2018
- Accepted in final form January 25, 2019
- First Published April 24, 2019.
Article Versions
- Previous version (April 24, 2019 - 12:45).
- You are viewing the most recent version of this article.
Author Disclosures
- Basil T. Darras, MD,
- Claudia A. Chiriboga, MD, MPH,
- Susan T. Iannaccone, MD,
- Kathryn J. Swoboda, MD, FACMG,
- Jacqueline Montes, PT, EdD, NCS,
- Laurence Mignon, PhD,
- Shuting Xia, MS,
- C. Frank Bennett, PhD,
- Kathie M. Bishop, PhD,
- Jeremy M. Shefner, MD, PhD,
- Allison M. Green, PhD,
- Peng Sun, PhD,
- Ishir Bhan, MD, MPH,
- Sarah Gheuens, MD, PhD,
- Eugene Schneider, MD,
- Wildon Farwell, MD, MPH and
- Darryl C. De Vivo, MD
- on behalf of the ISIS-396443-CS2/ISIS-396443-CS12 Study Groups
- Basil T. Darras, MD,
(1) Hoffman LaRoche (2) Cytokinetics, Inc. (3) BMS, Inc (4) Sarepta Therapeutics (5) Biogen (6) AveXis (6) PTC Therapeutics (7) AveXis Ad hoc SAB member; no financial interests in these companies
NONE
Speaker honoraria from Biogen
NONE
NONE
(1) Various titles, UpToDate, 1999-present (2) One videotaped presentation,
NONE
NONE
Biogen
NONE
NONE
(1) PTC Therapeutics (2) Valerion Therapeutics (MTM) (3) Sarepta Therapeutics (4) Biogen (5) Summit (6) AveXis (7) Roche (8) Fibrogen (9) Santhera (10) Cytokinetics
(1) NIH/NINDS, 1U10NS077269, Site-PI/PD, 2018-2023. (2) NIH/NINDS, 5U01NS061799, FOR-DMD, Site-PI, 2012-2016. (3) NIH/NINDS via Skulpt Inc., 5RNS073188, Site-PI, 2015- 2016.
NONE
(1) SMA Foundation (2) Muscular Dystrophy Association (3) Slaney Family Fund for SMA
NONE
NONE
NONE
NONE
NONE
NONE
- Claudia A. Chiriboga, MD, MPH,
Advisory board member for Biogen, Avexis, Roche, Genentec
NONE
Biogen speaker honoraria 2018
NONE
NONE
NONE
NONE
NONE
Biogen speaker (see above)
NONE
NONE
research sponsors Biogen (CS11) Avexis-Strive and Sprint Roche Pharmaceuticals (Sunfish, Jewelfish)
NONE
NONE
SMA foundation- natural history study Cure SMA- Spinraza staff support MDA- MDA Care Center
NONE
NONE
NONE
NONE
NONE
NONE
- Susan T. Iannaccone, MD,
Member DSMB, Congenital Muscular Dystrophy Ascending Multiple Dose Cohort Study anaLyzing Pharmacokinetics at three dose Levels In Children and Adolescents with Assessment of Safety and Tolerability of Omigapil Santhera AveXis Ad Board Sarepta Ad Board
NONE
American Academy of Pediatrics, 2018
Editorial board: Neuromuscular Disorders, Journal of Pediatric Rehabilitation Medicine
NONE
NONE
NONE
NONE
NONE
NONE
NONE
Site PI for: PTC sponsored clinical trial of Ataluren in Duchenne muscular dystrophy: A Phase 2b Efficacy and Safety Study of PTC124 in Subjects with Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy Extension Study of Ataluren in Subjects with Nonsense- Mutation-Mediated Duchenne and Becker Muscular Dystrophy, PTC Therapeutics, 3 patients previously enrolled now in open label. 2011 - present An Open-Label, Multi-Center, 48-Week Study with a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy Sarepta 2014 - present Biogen SHINE, site coPI AveXis STRIVE, STRONG, SPRINT, site PI Capricor HOPE2, site PI
Site CoPI for NIH sponsored NeuroNEXT 2018-2023 Site CoPI for Wellstone Center for Muscular Dystrophy (NIH U54 AR068791-01 ) 2015-2020
NONE
Muscular Dystrophy Association, Care Center grant: coDirector Cure SMA Center of Excellence, coDirector
NONE
NONE
NONE
NONE
NONE
NONE
- Kathryn J. Swoboda, MD, FACMG,
Cure SMA Scientific Advisory Board AHC foundation Scientific Advisory Board Biogen Scientific Advisory Board
NONE
Biogen Ionis
1. Journal of Neuromuscular Disorders, Editorial Board, 2015- present
NONE
NONE
NONE
Biogen AveXis
NONE
NONE
NONE
1. Biogen: PI for NURTURE, phase 2 trial of nusinursen in pre- symptomatic infants with SMA; April 2016-present 2. AveXis: PI for SPR1NT, phase 3 Pre-Symptomatic Study of Intravenous AVXS-101 in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2; July 2018-present
NIH RO1-HD69045 for newborn screening pilot study for SMA, PI, 2011-18, NICHD And NIH R21-NS108015, NINDS, Pathologic studies in SMA, PI, 2018-2020
Professor, Adjunct, University of Utah Department of Neurology Lecturer, Harvard Medical School
Cure SMA clinical support grant, PI, 2018-2019 Cure SMA research grant, PI, 2018-2020
NONE
NONE
NONE
NONE
NONE
NONE
- Jacqueline Montes, PT, EdD, NCS,
(1) Roche Pharmaceuticals (2) Biogen (3)Cytokinetics (4) Scholar Rock
NONE
NONE
NONE
NONE
NONE
NONE
(1) Isis Pharmaceuticals (2) Biogen
NONE
NONE
NONE
NONE
National Institute of Health: Eunice Kennedy Shriver National Institute of Child Health and Human Development (K01HD084690), Principal Imvestigator; 2016-2021
NONE
(1) SMA Foundation (2) Muscular Dystrophy Association Clinical Trials Travel Grant (575870).
NONE
NONE
NONE
NONE
NONE
NONE
- Laurence Mignon, PhD,
NONE
NONE
NONE
NONE
NONE
NONE
(1) Ionis Pharmaceuticals, Inc, Director Clinical Development, 2013-2018
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Shuting Xia, MS,
NONE
NONE
NONE
NONE
NONE
NONE
Ionis Pharmaceuticals, associate director, 18 years
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- C. Frank Bennett, PhD,
NONE
NONE
NONE
NONE
Inventor on several issued patents covering nusinersen
NONE
Ionis Pharmaceuticals, Senior Vice President Research,Employed for 29 years
Experimental Therapeutic Center in Singapore Stock/Stock Options, Medical Equipment & Materials: Own stock and have stock options in Ionis Pharmaceuticals
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Kathie M. Bishop, PhD,
Unpaid scientific advisory board member for the non- profit groups the Myotonic Dystrophy Foundation and the Spinal Muscular Atrophy Foundation
NONE
NONE
NONE
NONE
NONE
I was a full-time employee of Isis Pharmaceuticals from September 2009 to March 2015. Currently a full-time employee of Otonomy Inc.
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Jeremy M. Shefner, MD, PhD,
I served on a Scientific Advisory Boards sponsored by Biogen-Idec, AveXis, Orphazyme, Brainstorm and Cytokinetics related to new ALS therapies. I am also the Medical Monitor for the Braingate Brain-Computer Interface Program.
NONE
non-profit: I received an honorarium for giving Grand Rounds Massachusetts General Hospital.
UpToDate, Neuromuscular Section Editor, 2007-present. Editorial Board, Neurotherapeutics and the ALS Journal.
NONE
UpToDate, Neuromuscular Section Editor, 2007-present.
NONE
Commercial: I have consulted for Cytokinetics, and Biohaven.
NONE
NONE
NONE
Biogen Idec, clinical trial management. Cytokinetics, clinical trial management and site investigator. Amylyx, clinical trial management Brainstorm, clinical trial management
NIH through subcontracts from the Massachusetts General Hospital, trial management. NIH: 1U24NS107204-01, Principal Investigator, 2018-2013
NONE
ALS Association,principal investigator of TREAT ALS grant and experimental markers of ALS progression grant. ALS Finding a Cure Foundation
NONE
NONE
NONE
NONE
NONE
NONE
- Allison M. Green, PhD,
NONE
NONE
NONE
NONE
NONE
NONE
Excel Scientific Solutions, Envision Pharma Group, medical writer, 2 years; Biogen provided funding for medical writing support in the development of this report to Excel Scientific Solutions.
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Peng Sun, PhD,
NONE
NONE
NONE
NONE
NONE
NONE
Biogen, Director of Biostatistics, 4 years
NONE
NONE
NONE
NONE
Biogen as an employee
NONE
NONE
NONE
NONE
NONE
NONE
Biogen, 4 years
NONE
NONE
- Ishir Bhan, MD, MPH,
NONE
NONE
NONE
NONE
NONE
NONE
I am an employee of Biogen (2 years)
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
Biogen (stock)
NONE
NONE
- Sarah Gheuens, MD, PhD,
NONE
NONE
NONE
NONE
NONE
NONE
Biogen, senior medical director, 6 years
NONE
NONE
I am an employee of Biogen and hold stock.
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Eugene Schneider, MD,
NONE
NONE
NONE
NONE
NONE
NONE
Ionis Pharmaceuticals, VP Clinical Development, 2013-present
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
Ionis Pharmaceuticals - employee and stock-holder
NONE
NONE
- Wildon Farwell, MD, MPH and
NONE
NONE
NONE
NONE
NONE
NONE
I am an employee of Biogen. My employment with Biogen begn in 2010.
NONE
NONE
NONE
NONE
I am an employee of Biogen.
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
NONE
- Darryl C. De Vivo, MD
SMA Foundation. The Hope for Children Research Foundation. Pediatric Neurotransmitter Disease Association. International Reye Syndrome Foundation. The Will Foundation Chairman, Data Safety Monitoring Board, Cytokinetics Chairman, Canavan Disease Foundation Advisory Board, NYC Scientific Advisory Board, Metafora Glut1 Deficiency Foundation The Grace Science Foundation
NONE
Speaker Honorarium from the American Academy of Neurology
Current Opinion in Neurology, Editorial Board Medlink in Neurology, Editorial Board Journal of Pediatric Neurology Editorial Board (Turkish journal)
Gene therapy for Glut1 Deficiency patent International PCT Patent Application No. PCT/US2016/021810 Based on U.S. Provisional Patent Application Serial No.: 62/130,899 Title: RECOMBINANT GLUT1 ADENO-ASSOCIATED VIRAL VECTOR CONSTRUCTS AND RELATED METHODS FOR RESTORING GLUT1 EXPRESSION Filed: March 10, 2016 Our Ref.: 01001/003887-WO0
Elsevier Publishers. Lippincott Publishers.
NONE
Ionis Pharmaceuticals Biogen Pharmaceuticals Ultragenyx Pharmaceuticals
NONE
NONE
NONE
Ionis Pharmaceuticals Biogen Pharmaceuticals Ultragenyx Pharmaceuticals Sarepta Therapeutics PTC Therapeutics
NIH, DOD
NONE
SMA Foundation. The Hope for Children Research Foundation. The Will Foundation The Pediatric Neurotransmitter Disease Association The Glut1 Deficiency Foundation
NONE
NONE
NONE
NONE
NONE
Expert witness.
- From the Department of Neurology (B.T.D.), Boston Children's Hospital, MA; Departments of Neurology (C.A.C., J.M., D.C.D.), Pediatrics (C.A.C., D.C.D.), and Rehabilitation and Regenerative Medicine (J.M.), Columbia University Irving Medical Center, New York, NY; Department of Pediatrics (S.T.I.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (K.J.S.), Massachusetts General Hospital, Boston; Ionis Pharmaceuticals, Inc. (L.M., S.X., C.F.B., E.S.), Carlsbad, CA; employee of Ionis Pharmaceuticals, Inc. (K.M.B.), Carlsbad, CA, during design and conduct of this study, current employee of Otonomy, San Diego, CA; Department of Neurology (J.M.S.), Barrow Neurologic Institute, Phoenix, AZ; Excel Scientific Solutions (A.M.G.), Southport, CT; and Biogen (P.S., I.B., S.G., W.F.), Cambridge, MA.
- Correspondence
Dr. Darras basil.darras{at}childrens.harvard.edu
Article usage
Cited By...
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study
Dr. Robert Shapiro and Dr. Amynah Pradhan