Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis
The BeatMG Study
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Article Information
- Received July 1, 2020
- Accepted in final form November 19, 2021
- First Published December 2, 2021.
Article Versions
- Previous version (December 2, 2021 - 12:45).
- You are viewing the most recent version of this article.
Author Disclosures
- Richard J. Nowak, MD,
- Christopher S. Coffey, PhD,
- Jonathan M. Goldstein, MD,
- Mazen M. Dimachkie, MD,
- Michael Benatar, MD, PhD,
- John T. Kissel, MD,
- Gil I. Wolfe, MD,
- Ted M. Burns, MD,
- Miriam L. Freimer, MD,
- Sharon Nations, MD,
- Volkan Granit, MD,
- A. Gordon Smith, MD,
- David P. Richman, MD,
- Emma Ciafaloni, MD,
- Muhammad T. Al-Lozi, MD,
- Laura Ann Sams, MD,
- Dianna Quan, MD,
- Eroboghene Ubogu, MD,
- Brenda Pearson, BS,
- Aditi Sharma, MBBS,
- Jon W. Yankey, MS,
- Liz Uribe, MS,
- Michael Shy, MD,
- Anthony A. Amato, MD,
- Robin Conwit, MD,
- Kevin C. O'Connor, PhD,
- David A. Hafler, MD,
- Merit E. Cudkowicz, MD,
- Richard J. Barohn, MD;
- on behalf of the NeuroNEXT NN103 BeatMG Study Team
- Richard J. Nowak, MD,
(1) Ra Pharma, (2) Alexion, (3) argenx, (4) Immunovant, (5) Momenta
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(1) Grifols, (2) Alexion
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(1) Alexion, (2) Grifols, (3) Ra Pharma, (4) Momenta, (5) Immunovant, (6) CSL Behring
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(1) While drug/placebo were provided by Genentech through an investigator-initiated trial agreement with Dr. Nowak, they were not involved in trial design, implementation or data analysis. (2) Dr. Nowak is Global Principal Investigator for a phase 3 trial in myasthenia gravis through a research agreement(Viela Bio, a part of Horizon Therapeutics).
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(1) Alexion, (2) Genentech, (3) Grifols, (4) Ra Pharma, (5) argenx, (6) Momenta, (7) Immunovant, (8) Viela Bio
(1) National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health under award number U01NS084495, PI, 2013-2019
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(1) Myasthenia Gravis Foundation of America (MGFA)
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- Christopher S. Coffey, PhD,
(1) Several NIH Sponsored DSMBs
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(1) Michael J Fox Foundation for Parkinson's Research, Funding for travel to meetings
(1) Clinical Trials, Associate Editor (2) Trials, Associate Editor (3) Stroke, Statistical Editor
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(1) NIH U24 NS112873, Co-PI, 2019-2023 (2) NIH U01 NS077352, Principal Investigator, 2011-2023 (3) NIH R25 HL131467, Co-Investigator, 2016-2022 (4) NIH U01 NS096767, Principal Investigator (Subcontract), 2016-2022 (5) NIH U01 NS095388, Principal Investigator (Subcontract), 2017-2022 (6) NIH U01 AR070498, Principal Investigator (Subcontract), 2017-2022 (7) NIH U01 NS114001, Principal Investigator (Subcontract), 2019-2022
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(1) The Michael J Fox Foundation for Parkinson's Research
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- Jonathan M. Goldstein, MD,
1.Advisory board Alexion pharmaceutical
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NINDS, U01NS084495, Investigator, 2013-2019
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- Mazen M. Dimachkie, MD,
Dr. Dimachkie serves or recently served as a consultant for Amazentis, ArgenX, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, Roivant Sciences Inc, RMS Medical, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Third Rock and UCB Biopharma. Dr. Dimachkie received research grants or contracts from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark, UCB Biopharma, Viromed/Healixmith & TMA.
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Dr. Dimachkie serves or recently served as a consultant for Amazentis, ArgenX, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, Roivant Sciences Inc, RMS Medical, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Third Rock and UCB Biopharma. Dr. Dimachkie received research grants or contracts from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark, UCB Biopharma, Viromed/Healixmith & TMA.
Journal of Clinical Neuromuscular Disease; Editorial Board Member Reviewer: Frontiers in Neurology
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Dr. Dimachkie serves or recently served as a consultant for Amazentis, ArgenX, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, Roivant Sciences Inc, RMS Medical, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Third Rock and UCB Biopharma. Dr. Dimachkie received research grants or contracts from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark, UCB Biopharma, Viromed/Healixmith & TMA.
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Dr. Dimachkie received research grants or contracts or educational grants from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, UCB Biopharma / RaPharma, Viromed/Healixmith & TMA. Dr. Dimachkie received research grants or contracts from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark, UCB Biopharma, Viromed/Healixmith & TMA.
NIH FDA-OOPD
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- Michael Benatar, MD, PhD,
(1) Viela Bio (2) Immunovant (3) Alexion (4) UCB (5) SANOFI (6)Biogen (7) Denali (8) Orphazyme (9) Novartis (10) Alector
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US Provisional Patent Application. Determining onset of amyotrophic lateral sclerosis
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(1) National Institutes of Health (U24 NS107376), PI, 2018-2023 (2 National Institutes of Health (U54 NS092091), PI, 2014-2024 (3) National Institutes of Health (U01 NS107027), PI, 2018-2023 (4) National Institutes of Health (R01 NS205479), PI, 2018-2023 (5) National Institutes of Health (R21 NS111275), Co-I, 2019-2021
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(1) ALS Association (16-TACL-242) (2) MDA (376132) (3) Target ALS
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- John T. Kissel, MD,
Member of Data Safety Monitoring Board for NIH NeuroNext Study $0-$4,999
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Oxford Press: 2004-present
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- Gil I. Wolfe, MD,
(1)UCB/Ra Scientific Advisory Board (2)ArgenX Scientific Advisory Board (3)BPL Scientific Advisory Board (4)Orphazyme DSMB (5)Alexion Scientific Advisory Board
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(1) Grifols speaker honoraria (2) Alexion speaker honoraria
RRNMF Neuromuscular Journal, Editorial Board member, 2020-2021
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As above under #3
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(1) UCB/Ra Pharma for research support (2) Immunovant for research support (3) ArgenX for research support (4) Roche for research support
PCORI: 1609-35953, PROMISE-MG: Prospective multicenter observational cohort study of comparative effectiveness of disease-modifying treatments for myasthenia gravis (Site Principal Investigator, PI D. Sanders). 1/1/18- 12/31/19, Per patient reimbursement $3600.
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MG Foundation of America
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- Ted M. Burns, MD,
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- Miriam L. Freimer, MD,
Commercial: Alexion, ARGENX, UCB
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Commercial: alexion Amicus Alnylum Orphyzyme Fulcrum UCB Takeda
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- Sharon Nations, MD,
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- Volkan Granit, MD,
(1)Myasthenia Gravis Foundation of America (2)Argenx (3)Alexion Pharmaceuticals (4)Immunovant Sciences GMBH
NONE
NONE
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(1)Argenx (2)Immunovant Sciences GMBH
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(1) McAloon&Friedman, Expert Witness, 2018 (2) Jackson Kelly PLLC, Expert Witness, 2019
- A. Gordon Smith, MD,
Lexicon DSMB NIH DSMB Disarm Therapeutics Study Steering Committee Co-Chair Eidos DSMB
NONE
NONE
Continuum Editorial Board Annals of Clinical and Translational Neurology Editorial Board
NONE
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(1) Merz (2) Disarm Therapeutics (3) Alexion (4) Argenx
(1) Alexion
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(1) DK064814 PI 2004-2020 NIDDK (2) U01NS0953880 PI 2017-2021 NINDS
NONE
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- David P. Richman, MD,
Cabaletta Bio
NONE
NONE
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Cabaletta bio Sponsored Research Agreement
NINDS, 1 R21 NS104516-01, Principal Investigator, 7/1/18- 6/30/21.
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Myasthenia Gravis Foundation of America
NONE
NONE
NONE
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- Emma Ciafaloni, MD,
Sarepta Avexis Stronbridge NS Pharma Biogen Santhera PTC Alexion Wave Sanofi Scholar Rock
NONE
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MedLink
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Oxford Press
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Center Disease Control Prevention:
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Sarepta, PTC, Santhera, Orphazyme: clinical trial support
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- Muhammad T. Al-Lozi, MD,
NONE
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- Laura Ann Sams, MD,
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- Dianna Quan, MD,
Alnylam Pharmaceuticals
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Pfizer, travel to PI meeting (commercial entity) AANEM, speaker honoraria
Neurology Today, Editorial Board
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Diabetic Neuropathy, eMedicine, current online, royalties Ocular Myasthenia Gravis, UpToDate, current online, royalties
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IngenioRx
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Alnylam Pfizer Ionis Cytokinetics Argenx Momenta Alexion VielaBio
NONE
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- Eroboghene Ubogu, MD,
NONE
NONE
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Ubogu EE. Neurology Oral Boards Review: A Concise and Systematic Approach to Clinical Practice, Humana Press, Totowa, August 2005. ISBN: 1-58829-654-7 (paperback version), ISBN: 1-59259-984-2 (e-Book version). Cardona AE, Ubogu EE (eds.) Chemokines: Methods and Protocols, Methods in Molecular Biology, Springer Science + Business Media, New York 2013. ISBN: 978-1-62703-425-8 (hardback version), ISBN: 978-1-62703-426-5 (eBook), DOI: 10.1007/978-1-62703-426-5.
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1) Commercial entity: Latigo Biotherapeutics (specialist advice on the blood-nerve barrier permeability and neuropathic pain therapeutics).
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(1) Argenx BVBA, (2) Genzyme Corporation
(1) NIH/NINDS, R21 NS109644-01A1, Principal Investigator, 2019-2021, (2) NIH/NINDS, R21 NS113033-01A1, Principal Investigator, 2020-2022, (3) NIH/NINDS, R01 NS116704-01, Subcontract Principal Investigator/ Co-Investigator, 2020- 2024, (4) NIH/NINDS, U01 NS095388, Site Principal Investigator, 2018-2023, (5) NIH/NINDS, R01NS090083Â06, Site Principal Investigator, 2016-2020
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(1) SV40 Large T-antigen immortalized human endoneurial endothelial cell line, Baylor Licensing Group, 2021
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- Brenda Pearson, BS,
NONE
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- Aditi Sharma, MBBS,
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- Jon W. Yankey, MS,
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- Liz Uribe, MS,
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Everest Clinical Research, Senior Biostatistician 1, 2 years
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- Michael Shy, MD,
(1) Charcot Marie Tooth Association-Non Profit (2) Muscular Dystrophy Association (MDA)-Non Profit
NONE
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Neuromuscular Disorders, Editorial Board Muscle and Nerve, Editorial Board
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(1) Alnylam Pharmaceuticals - Consultant (2) Mitochondria in Motion-Consultant (3) Inflectis BioSci - Consultant (4) Neurogene - Consultant (5) Applied Therapeutics - (Consultant)
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NINDS/Office of Rare Disease/NCATS
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(1) Muscular Dystrophy Association; (2) Charcot Marie Tooth Association
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- Anthony A. Amato, MD,
Medical Advisory Board for Orphazyme, Argenx, Ra Pharma, Johnson and Johnson
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Associate Editor for Neurology
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Amato AA, Russell J. Neuromuscular Disease (2nd Ed). New York: McGraw-Hill, 2016 Harrisons Principles of Internal Medicine, New York, McGraw-Hill, 2021 (in-press) Up-to-Date
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Medical Consultant for Best Doctors
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Expert witness for defendant in medical malpractice cases
- Robin Conwit, MD,
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- Kevin C. O'Connor, PhD,
Commercial entity - Alexion, now part of AstraZeneca
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Commercial entities: Consultant/advisor for Alexion Pharmaceuticals, Takeda, and for Roche.
Received speaking fees from Alexion and Viela Bio, now part of Horizon Therapeutics.
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Received research support from Ra Pharma and is a consultant and equity shareholder of Cabaletta Bio. KOÂC is the recipient of a sponsored research subaward from the University of Pennsylvania, the primary financial sponsor of which is Cabaletta Bio. Received research support from Ra Pharma, now a part of UCB Pharma, and Alexion, now part of AstraZenca, and Viela Bio, now part of Horizon Therapeutics.
Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) through awards R01-AI114780 and R21-AI142198, NIH through the Rare Diseases Clinical Research Consortia of the NIH (Award Number U54-NS115054)
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1. Guthy Jackson Charitable Organization 2. A Neuromuscular Disease Research Program award from the Muscular Dystrophy Association (MDA) under award number MDA575198.
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Equity shareholder of Cabaletta Bio.
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- David A. Hafler, MD,
D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, ARCUS, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme.
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D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, ARCUS, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme.
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Funded as PI or Co-PI by NIH grants (1) P01AI073748, 2008- 2013, (2)P01 AI045757,2013-2018, (3) R01 NS049477, 2010- 2015, (4) R01 AI091568, 2010-2015, (5) U19 AI089992, 2010- 2022,(6) P01 AI039671, 2010-2022, (7) R25 NS079193, 2012- 2022, (8) U01 AI02011, 2012-2017, (9) U01NS084495-01A1, 2013-2017, Funded as Co-PI by Department of the Army grant # MS110275, 2012-2013
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Funded as PI by (1) National Multiple Sclerosis Society grant # CA 1061-A-18, 2009-2019, (2) Nancy Taylor Foundation grant, 2011-2013
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- Merit E. Cudkowicz, MD,
Lilly DSMB
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Neurotherapeutics editorial board JAMA Neurology editorial board
Metabolomics in ALS - patent MIR 155 inhibitor - patent
UptoDate MND chapter
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Cytokinetics, Biogen, Orion, ImmunityPharm, Biohaven, Avexis, Revalesio, MT Pharma
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NINDS - U01 NeuroNEXT
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Muscular dystrophy association, als association, als finding a cure foundation, ALS One
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- Richard J. Barohn, MD;
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(1) Journal of Clinical Neuromuscular Disease, Associate Editor, 2002-Present (2) RRNMF Neuromuscular Journal, editor
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(1) Novartis, (2) Sanofi/Genzyme, (3) Biomarin, (4) Ionis, (5) Teva, (6) Cytocenetics, (7) Eli-Lily
(1) NIH/NCATS, UL1 TR000001, PI, 2011Â2018, (2) FDA OPD, RO1FD003739, PI, 2012-2017, (3) NIH/NINDS, 1U10NS077356, PI, 2011-2018, (4) NIH, U54TR001137, Co-Investigator, 2014-2019, (5) PCORI, CER-1306-02496, PI, 2014-2018, (6) FDA OPD, RO1FD003937, PI, 2016-2019, (7) PCORI, CDRN-1501-26643, Co- Investigator, 2015-2018.
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- on behalf of the NeuroNEXT NN103 BeatMG Study Team
- From the Department of Neurology (R.J.N., A.S., K.C.O., D.A.H.), Yale University School of Medicine, New Haven, CT; Clinical Trials Statistical & Data Management Center (C.S.C., B.P., J.W.Y., L.U.) and Department of Neurology (A.S.), University of Iowa, Iowa City; Department of Neurology (J.M.G.), Hospital for Special Surgery, New York, NY; Department of Neurology (M.M.D., R.J.B.), Kansas University School of Medicine, Kansas City; Department of Neurology (M.B., V.G.), University of Miami Miller School of Medicine, FL; Department of Neurology (J.T.K., M.L.F.), The Ohio State University Wexner Medical Center, Columbus; Department of Neurology (G.I.W.), University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY; Department of Neurology (T.M.B.), University of Virginia School of Medicine, Charlottesville; Department of Neurology (S.N.), University of Texas Southwestern Medical School, Dallas; Department of Neurology (V.G.), Albert Einstein College of Medicine, Bronx, NY; Department of Neurology (A.G.S.), University of Utah School of Medicine, Salt Lake City; Department of Neurology (D.P.R.), University of California Davis School of Medicine, Sacramento; Department of Neurology (E.C.), University of Rochester School of Medicine & Dentistry, NY; Department of Neurology (M.T.A.-L.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (L.A.S.), University of Cincinnati College of Medicine, OH; Department of Neurology (D.Q.), University of Colorado School of Medicine, Aurora; Department of Neurology (E.U.), The University of Alabama at Birmingham School of Medicine; Department of Neurology (M.S.), Carver College of Medicine, University of Iowa, Iowa City; Department of Neurology (A.A.A.), Brigham and Women's Hospital, Boston, MA; Division of Clinical Research (R.C.), National Institute of Neurological Disorders and Stroke, Rockville, MD; Department of Neurology (M.E.C.), Massachusetts General Hospital, Boston; and Department of Neurology (R.J.B.), University of Missouri, Columbia.
- Correspondence
Dr. Nowak richard.nowak{at}yale.edu
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