• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar
  • Skip to footer
  • Email
  • Facebook
  • LinkedIn
  • Twitter
  • YouTube

International Alliance of ALS/MND Associations

  • Members' Login
  • Contact
  • Join the Alliance
  • Donate
  • What is ALS/MND
  • Find a Member Association
  • Support for PALS & CALS
    • Fundamental Rights for People with ALS/MND and Caregivers
    • Research
      • Voice Preservation
      • Open Science
      • Expanded Access
      • Understanding ALS/MND Research
      • Improving Regulatory Pathways
      • Right to Try
      • US FDA Orphan Drug Designation
      • Unproven (Off-Label) Treatments
      • Open Label Extension
    • Advocacy
      • Advocacy Toolkit
      • Emergency Preparedness Toolkit
      • Equitable Access to Therapies
      • Recommendations for Trial Sponsors
    • Clinical Care
      • Genetic Counselling & Testing
      • Mental Health Support
      • Nursing and Symptom Management
      • Nutrition and Swallowing
      • Occupational Therapy and Activities of Daily Living
      • Physiotherapy and Mobility
      • Respiratory Care
      • Speech Therapy and Communication
      • Support for Family & Caregivers
      • Technology
      • Global Clinic Locator
    • Drugs in Development
      • AB Science – Masitinib
      • BrainStorm Cell Therapeutics – NurOwn
      • Clene Nanomedicine – CNM-Au8
      • Collaborative Medicinal Development – CuATSM
      • ILB – Tikomed
      • Kadimastem – AstroRx
      • Mitsubishi Tanabe Pharma America – Oral Edaravone
      • Neuronata-R/Lenzumestrocel
      • NeuroSense – PrimeC
      • Neuvivo – NP001
      • Prilenia Therapeutics – Pridopidine
      • SOD1 Therapies & Trials
      • T Regulatory Cell Therapies
      • Ulefnersen – Ionis Pharmaceuticals
    • Approved Drugs
      • Nuedexta
      • Radicava/Edaravone
      • Riluzole/Tiglutik
      • Rozebalamin/Methylcobalamin
      • Tofersen/Qalsody
    • Drugs No Longer in Development
      • Amylyx – AMX0035
      • Collaborative Medicinal Development – CuATSM
      • Cytokinetics – Reldesemtiv
      • Orphazyme – Arimoclomol
      • TUDCA Trial
  • Support for Health Professionals
    • Breaking the News in ALS/MND
    • Diagnostic Delay (in development)
  • Events/Programs
    • Calendar of Events/Programs
    • Alliance Meeting
    • Allied Professionals Forum
    • Alliance Webinars
    • ALS/MND Connect
    • Global Day Calendar
    • March of Faces
    • Patient Fellows Program
    • Global CRLI
    • International Symposium
  • About
    • Who We Are
    • ALS/MND Health Literacy Map
    • Board of Trustees
    • Advisory Councils/Committees
      • Scientific Advisory Council
      • PALS and CALS Advisory Council
      • Innovation and Technology Council
      • Advocacy and Public Policy Forum
      • Research Directors Forum
      • Governance Committee
      • Finance Committee
    • Staff
    • History
    • Archives
      • Newsletters
      • Meetings
    • Awards
      • Forbes Norris Award
      • Humanitarian Award
      • Allied Health Professional Award
      • Student Innovation Award
  • Members
    • Member Registration
    • Forgot Password

Methylcobalamin

Background

Methylcobalamin is the biologically active form of vitamin B12 and is used in Japan to treat peripheral neuropathy and megaloblastic anaemia. Methylcobalamin has the ability to decrease levels of homocysteine, a molecule that can contribute to neuronal degeneration which led to it being considered as a potential candidate for ALS/MND treatment.

Based on some small early-stage human studies, a Japanese pharmaceutical company, Eisai, supported a Phase II/III clinical trial.

This trial was run between 2007 and 2014 in 51 sites in Japan with 360 participants. The treatment regime was quite long (3.5 years), with participants receiving placebo, or 25 or 50mg methylcobalamin twice a week via intramuscular injections. Results from this initial trial showed that receiving methylcobalamin did not lead to any significant differences either in survival rates or ALS/MND functional scores, when compared with placebo.

However, subsequent analysis of the data showed that methylcobalamin seemed to have an effect in a sub-group of participants who received treatment earlier in their disease journey (a year or less after symptom onset). These participants showed a statistically significant decrease in the rate of disease progression (i.e., a decrease in the rate of decline of the ALSFRS-R score), and also survived longer or took longer to require ventilation support compared with the placebo group. The outcome of the trial was published in January 2019 (“Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study”).

However, this data was not considered sufficient for approval as an ALS/MND treatment by the Japanese authorities because it was done after the initial study results were obtained (post-hoc analysis) and such observations can be misleading.

In an attempt to validate the post-hoc findings, a new Phase 3 trial, JETALS, was undertaken in 2017, which focused on participants who seemed to respond well to the treatment from the first trial, i.e. those whose symptoms had begun within one year of enrollment and who progressed at a moderate rate (defined as a 1–2 point decrease in their ALSFRS-R scores over the three months preceding the trial).

Trial Design & Results

Participants received twice-weekly injections of either 50 mg of methylcobalamin or a placebo for 16 weeks. An open-label extension was then made available to all trial participants in which they will receive the therapy until March 2024.

The initial 16-week trial met its primary outcome, with methylcobalamin-treated participants showing a 43% slower disease progression as measured by their ALSFRSR scores than those given a placebo (2.66 vs. 4.63 points over 16-weeks). Participants receiving Riluzole as well as methylcobalamin showed similar results. There was no difference in side effects of the drug between placebo or methylcobalamin-treated participants. Although there were statistically significant reductions in ALSFRS-R, other measures such as muscle strength, forced vital capacity and the ALSAQ-40 total score, were not changed.

The results from this trial were published in May 2022: “Efficacy and Safety of Ultra-high-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis A Randomized Clinical Trial.”

There are several things to take into account for this study. As the drug was only tested on participants early in the disease process, it is not clear if the treatment would be appropriate for participants with more advanced disease. Methylcobalamin treatment results in a marked change in urine colour which could mean that participants may have known whether they were receiving placebo or methylcobalamin and that could influence results (including a potential “nocebo” effect). The fact that the placebo group appeared to worsen their rate of disease progression once the trial commenced perhaps supports these concerns of a potential unblinding effect. The open label extension data may well help to offset any possible confounding effects. It should be considered that the 16-week trial duration is shorter than most other trials which usually have a minimum 24-week duration.

Data from the open-label extension will be informative for the longer-term benefits of this drug.

Summary

The Scientific Advisory Council (SAC) believes that the initial trial and follow-up stage 3 trial have demonstrated promising results in a subset of early stage participants. The company have stated they will file for approval from the Japanese authorities in 2023. Due to the short trial duration and potential confounding effects (hastened placebo decline, possible unblinding), it is difficult at this time to know the true efficacy, if any, of ultra high-dose methylcobalamin in ALS/MND and any consideration of use should be at a clinician’s discretion. The SAC suggests that data from the open label extension be incorporated into analysis to better assess the efficacy of this treatment.

International Alliance of ALS/MND Associations
March 2023


The original language of communication is English and any translation cannot be guaranteed for accuracy of messaging.

 

Primary Sidebar

Drugs in Development

  • AB Science – Masitinib
  • BrainStorm Cell Therapeutics – NurOwn
  • Clene Nanomedicine – CNM-Au8
  • Collaborative Medicinal Development – CuATSM
  • ILB – Tikomed
  • Kadimastem – AstroRx
  • Methylcobalamin
  • Mitsubishi Tanabe Pharma America – Oral Edaravone
  • Neuronata-R/Lenzumestrocel
  • NeuroSense – PrimeC
  • Neuvivo – NP001
  • Prilenia Therapeutics – Pridopidine
  • SOD1 Therapies & Trials
  • T Regulatory Cell Therapies
  • Ulefnersen – Ionis Pharmaceuticals

  • Anita Forte, Les Turner ALS Foundation, USA

    Anita Forte, Les Turner ALS Foundation, USA

  • Emilienne Verhaegen, ALS Liga Belgium, Diagnosed 2014

    Emilienne Verhaegen, ALS Liga Belgium, Diagnosed 2014

  • Sam Hayden-Harler, Motor Neurone Disease (MND) Association, UK

    Sam Hayden-Harler, Motor Neurone Disease (MND) Association, UK

  • Peng Yi-Wen

    Peng Yi-Wen

  • Eric Von Schaumburg, USA

    Eric Von Schaumburg, USA

  • Sharon Corosanite, Diagnosed 2014 , ALS Hope Foundation, USA

    Sharon Corosanite, Diagnosed 2014 , ALS Hope Foundation, USA

  • Fabio Carvalho

    Fabio Carvalho

  • Guoqiang Xu, Diagnosed 2016 , Shaanxi ALS Association, China

    Guoqiang Xu, Diagnosed 2016 , Shaanxi ALS Association, China

  • Erwin Coppejans, Diagnosed 2007 , ALS Liga België, Belgium

    Erwin Coppejans, Diagnosed 2007 , ALS Liga België, Belgium

  • Richard Clark, MND New Zealand,  Diagnosed 2011

    Richard Clark, MND New Zealand, Diagnosed 2011

  • Duncan Bayly , MND Australia

    Duncan Bayly , MND Australia

  • Kirsty Gerlach, MND New Zealand, Diagnosed 2017

    Kirsty Gerlach, MND New Zealand, Diagnosed 2017

  • Ian Gale, MND Australia

    Ian Gale, MND Australia

  • Maurice Leclerc, Canada

    Maurice Leclerc, Canada

  • March of Faces Photo Submission_OLGA_ELA ARGENTINA

    March of Faces Photo Submission_OLGA_ELA ARGENTINA

  • Kris Van Reusel, Belgium

    Kris Van Reusel, Belgium

  • Marcelo Farinelli, Diagnosed 2006, ABrELA, Brazil

    Marcelo Farinelli, Diagnosed 2006, ABrELA, Brazil

  • Mahmood Anwar, UK

    Mahmood Anwar, UK

  • Oliver Juenke, DGM, Germany

    Oliver Juenke, DGM, Germany

  • Horacio Fritzer, Argentina

    Horacio Fritzer, Argentina

  • Chris McCauley, Diagnosed 2015 , ALS Canada

    Chris McCauley, Diagnosed 2015 , ALS Canada

  • Elisabeth Zahnd, Switzerland

    Elisabeth Zahnd, Switzerland

  • John Dinon, MND Australia

    John Dinon, MND Australia

  • Ailsa Malcolm-Hutton, Diagnosed 2013,  MND Association of England, Wales and N Ireland

    Ailsa Malcolm-Hutton, Diagnosed 2013, MND Association of England, Wales and N Ireland

  • Angela Jansen, Deutsche Gesellschaft für Muskelkranke e.V.-DGM, Diagnosed 1995, Germany

    Angela Jansen, Deutsche Gesellschaft für Muskelkranke e.V.-DGM, Diagnosed 1995, Germany

  • Kirsten Harley,  Diagnosed 2013,  Australia

    Kirsten Harley, Diagnosed 2013, Australia

  • Brian Lovell, Diagnosed 2011 . MND Australia

    Brian Lovell, Diagnosed 2011 . MND Australia

  • Imelda Arenas, ACELA, Colombia

    Imelda Arenas, ACELA, Colombia

  • Danny Reviers, Diagnosed 1979 , ALS Liga België, Belgium

    Danny Reviers, Diagnosed 1979 , ALS Liga België, Belgium

  • Laurie Petit-Jean, Diagnosed 2012 , ARSLA, France

    Laurie Petit-Jean, Diagnosed 2012 , ARSLA, France

  • Rosie Riley, Les Turner ALS Foundation, USA

    Rosie Riley, Les Turner ALS Foundation, USA

  • Liong Ting Ngu, MND Malaysia, Diagnosed 2014

    Liong Ting Ngu, MND Malaysia, Diagnosed 2014

  • Joy Blakeley, Diagnosed 2017 , MND Australia

    Joy Blakeley, Diagnosed 2017 , MND Australia

  • Ian Roberts

    Ian Roberts

  • Tammy Moore and Eddy Lefrancois

    Tammy Moore and Eddy Lefrancois

  • Irene McCaughey, Diagnosed 2011,  MND Australia

    Irene McCaughey, Diagnosed 2011, MND Australia

  • Mike Rannie,  ALS Canada,  Diagnosed 2017

    Mike Rannie, ALS Canada, Diagnosed 2017

  • March of Faces Photo Submission_ALEX_ELA ARGENTINA

    March of Faces Photo Submission_ALEX_ELA ARGENTINA

  • Den Haag, Diagnosed 2016 , The Netherlands

    Den Haag, Diagnosed 2016 , The Netherlands

  • Willi Klein

    Willi Klein

  • 727747090571358167

    727747090571358167

  • Jan Zuring, Diagnosed 2010 , The Netherlands

    Jan Zuring, Diagnosed 2010 , The Netherlands

  • Wendy Hendrickson, ALS Hope Foundation, USA

    Wendy Hendrickson, ALS Hope Foundation, USA

  • Steve

    Steve

  • Enzo Maccarrone, AISLA ONLUS, Italy

    Enzo Maccarrone, AISLA ONLUS, Italy

  • Chen Yin Xue, Taiwan MND Association, Diagnosed 1995, Taiwan

    Chen Yin Xue, Taiwan MND Association, Diagnosed 1995, Taiwan

  • Rolf Mauch, Association ALS Switzerland, Diagnosed 2015

    Rolf Mauch, Association ALS Switzerland, Diagnosed 2015

  • David Bishop

    David Bishop

  • Michel Perrozzo, ARSLA, Diagnosed 2015, France

    Michel Perrozzo, ARSLA, Diagnosed 2015, France

  • Dawn Morton, Diagnosed 2014 , MND Scotland, UK

    Dawn Morton, Diagnosed 2014 , MND Scotland, UK

Learn more about the March of Faces

Latest Tweets

  • Just now

Footer

Subscribe to our Bi-Monthly Newsletter

Sign up to receive updates and to hear what's going on in the International Alliance of ALS/MND Associations.

"*" indicates required fields

 
This field is for validation purposes and should be left unchanged.
  • Email
  • Facebook
  • LinkedIn
  • Twitter
  • YouTube
Return to top of page

Contact | Disclaimer | Privacy Notice & Cookies | Sitemap

Copyright © 2025 The International Alliance of ALS/MND Associations. All rights reserved.


Registered in England: Charity Number 1079504 · Site built by graphics.coop · Powered by WordPress · Members' login