Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

April 18, 2017; 88 (16 Supplement) April 25, 2017

AVXS-101 Phase 1 Gene Therapy Clinical Trial in SMA Type 1: Event Free Survival and Achievement of developmental milestones (CT.003)

Jerry Mendell, Samiah A. Al-Zaidy, Richard Shell, W. David Arnold, Louise R. Rodino-Klapac, Thomas W. Prior, Linda Lowes, Lindsay N. Alfano, Katherine Berry, Kathleen Church, John Kissel, Sukumar Nagendran, James L’Italien, Doug M. Sproule, Minna Du, Jessica A. Cardenas, Arthur Burghes, Kevin D. Foust, Kathrin Meyer, Shibi Likhite, Brian K. Kaspar
First published April 17, 2017,
Jerry Mendell
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
3Department of Neurology Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samiah A. Al-Zaidy
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Shell
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. David Arnold
3Department of Neurology Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Louise R. Rodino-Klapac
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
3Department of Neurology Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas W. Prior
4Department of Pathology Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linda Lowes
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lindsay N. Alfano
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine Berry
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen Church
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Kissel
2Department of Pediatrics Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sukumar Nagendran
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James L’Italien
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Doug M. Sproule
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minna Du
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica A. Cardenas
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arthur Burghes
3Department of Neurology Columbus OH United States
5Department of Molecular and Cellular Biochemistry, The Ohio State University Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin D. Foust
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathrin Meyer
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shibi Likhite
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian K. Kaspar
1Center for Gene Therapy, Nationwide Children’s Hospital Columbus OH United States
2Department of Pediatrics Columbus OH United States
3Department of Neurology Columbus OH United States
6AveXis, Inc. Bannockburn IL United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Citation
AVXS-101 Phase 1 Gene Therapy Clinical Trial in SMA Type 1: Event Free Survival and Achievement of developmental milestones (CT.003)
Jerry Mendell, Samiah A. Al-Zaidy, Richard Shell, W. David Arnold, Louise R. Rodino-Klapac, Thomas W. Prior, Linda Lowes, Lindsay N. Alfano, Katherine Berry, Kathleen Church, John Kissel, Sukumar Nagendran, James L’Italien, Doug M. Sproule, Minna Du, Jessica A. Cardenas, Arthur Burghes, Kevin D. Foust, Kathrin Meyer, Shibi Likhite, Brian K. Kaspar
Neurology Apr 2017, 88 (16 Supplement) CT.003;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
0

Share

  • Article
  • Info & Disclosures
Loading

Abstract

Objective: Spinal muscular atrophy is a devastating, monogenic neurodegenerative disease that in its most severe form, SMA Type 1 (SMA1), afflicted children never sit unassisted, roll over or maintain head control. A natural history study of SMA1 children reported that none achieved a CHOP-INTEND score of ≥40 (with one transient exception at ~41) and 75% died or required permanent-ventilation by 13.6 months. This trial explores safety and efficacy of a single intravenous administration of gene therapy in SMA1.

Background: This is the first-ever gene therapy (AVXS-101) trial in SMA1, a rapidly lethal neurologic disease. AVXS-101 delivers the SMN gene in a single-dose via the AAV9 viral vector, which crosses the blood-brain-barrier.

Design/Methods: In this ongoing Phase 1 trial, 15 patients with SMA1 confirmed by genetic testing (with 2xSMN2 copies) were enrolled. Patients received an intravenous dose of AVXS-101 at 6.7e13 vg/kg (Cohort-1 n=3) or 2.0e14vg/kg (Cohort-2, n=12). The primary objective is safety and secondary objectives include survival (avoidance of death/permanent-ventilation) and ability to sit unassisted. CHOP-INTEND scores and motor milestones are additional objectives.

Results: AVXS-101 appears safe and to improve survival (15Sept16 cut-off). All patients are alive and only 1 patient, from Cohort 1, reached the pulmonary endpoint at 28.8 months of age. All patients reaching 13.6 months did so free of permanent ventilation. Patients in Cohort 2 demonstrated improvements in motor function: 11/12 have CHOP-INTEND scores >40 points, 11/12 have head control, and 8/12 sit unassisted. Two patients can crawl, stand and walk independently.

Conclusions: In contrast with the published natural history, a single intravenous administration of AVXS-101 appears to demonstrate a positive impact on the survival of both dosing cohorts and a dramatic, sustained impact on motor function in Cohort-2: 11/12 patients achieved CHOP-INTEND scores and motor milestones rarely or never seen in this population.

Study Supported by: AveXis, Inc.

Disclosure: Dr. Mendell has received personal compensation for activities with AveXis, Inc. and Sarepta Therapeutics as a consultant. Dr. Mendell has received research support from Sarepta Therapeutics Inc. and AveXis, Inc. Dr. Al-Zaidy has nothing to disclose. Dr. Shell has receivd personal compensation for activities AveXis, Inc. as an advisory board member. Dr. Arnold has received research support from Gilead Sciences. Dr. Rodino-Klapac has nothing to disclose. Dr. Prior has nothing to disclose. Dr. Lowes has received personal compensation for activities with AveXis, Inc., Bristol-Myers Squibb, Sarepta Therapeutics, and Pfizer as a consultant. Dr. Alfano has nothing to disclose. Dr. Berry has nothing to disclose. Dr. Church has nothing to disclose. Dr. Kissel has received personal compensation for activities with AveXis, Inc. Dr. Nagendran has received personal compensation for activities with AveXis, Inc. Dr. Nagendran holds stock and/or stock options in AveXis, Inc. Dr. L'Italien has received personal compensation for activities with AveXis, Inc. Dr. L'Italien holds stock and/or stock options in AveXis, Inc. Dr. Sproule has received personal compensation for activities with AveXis, Inc. as an employee. Dr. Sproule holds stock and/or stock options with AveXis, Inc. Dr. Du has received personal compensation for activities with AveXis, Inc. as an employee. Dr. Du hold stock and/or stock options with AveXis, Inc. Dr. Cardenas has received personal compensation for activities with AveXis, Inc. as an employee. Dr. Cardenas holds stock and/or stock options in AveXis, Inc. Dr. Burghes has received personal compensation for activities with AveXis, Inc., Novartis and Guide Point as a consultant, or member of the advisory board. Dr. Foust has received personal compensation for activities with AveXis, Inc. as an employee. Dr. Foust has received licensing fees from AveXis, Inc. Dr. Foust has received stock and/or stock options with AveXis, Inc. Dr. Meyer has nothing to disclose. Dr. Likhite has nothing to disclose. Dr. Kaspar has received personal compensation for activities with AveXis, Inc. as employee.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

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.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
  • Info & Disclosures
Advertisement

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease–Related Dementias

Dr. Sevil Yaşar and Dr. Behnam Sabayan

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 101 (14)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise