Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis
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Article Information
- Received May 28, 2018
- Accepted in final form January 31, 2019
- First Published May 22, 2019.
Article Versions
- Previous version (May 22, 2019 - 12:45).
- You are viewing the most recent version of this article.
Author Disclosures
- James F. Howard Jr, MD,
- Vera Bril, MD,
- Ted M. Burns, MD,
- Renato Mantegazza, MD,
- Malgorzata Bilinska, MD,
- Andrzej Szczudlik, MD,
- Said Beydoun, MD,
- Francisco Javier Rodriguez De Rivera Garrido, MD,
- Fredrik Piehl, MD, PhD,
- Mariarosa Rottoli, MD,
- Philip Van Damme, MD, PhD,
- Tuan Vu, MD,
- Amelia Evoli, MD,
- Miriam Freimer, MD,
- Tahseen Mozaffar, MD,
- E. Sally Ward, PhD,
- Torsten Dreier, PhD,
- Peter Ulrichts, PhD,
- Katrien Verschueren, MSc,
- Antonio Guglietta, MD,
- Hans de Haard, PhD,
- Nicolas Leupin, MD,
- Jan J.G.M. Verschuuren, MD, PhD;
- on behalf of the Efgartigimod MG Study Group
- James F. Howard Jr, MD,
(1) SAB (non-remunerative), Alexion Pharmaceuticals (2) SAB (non-remunerative), argenx BVBA (3) SAB (non-remunerative, Ra Pharmaceuticals (4) SAB (non-remunerative), Toleranzia AB
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(1) Alexion Pharmaceuticals, travel for investigator meetings, SAB meetings; honoraria for advisory training sessions (2) argenx BVBA, travel for investigator meeting, SAB meetings (3) Ra Pharmaceuticals, travel for investigator meeting, SAB meetings
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(1) Consultant (non-remunerative), Alexion Pharmaceuticals (2) Consultant (non-remunerative), argenx BVBA (3) Consultant (non-remunerative), Ra Pharmaceuticals (4) Consultant (non-remunerative), Toleranzia AB
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(1) Alexion Pharmaceuticals (2) argenx BVBA (3) Ra Pharmaceuticals
(1) PCORI Award #1609-35953/Duke Clinical Research Institute, Principal Site Investigator, 2018 ? 2021 (2) Centers for Disease Control, and Prevention (CDC) U01DD001116,Co-Investigator, 2014 ? 2019. (3) NIH U01-NS061799-01A2, Principal Site Investigator, 2013 ? 2021. (4) NIH NS079683-01A1, Inveseatigator, 2013 ? 2018. (5) NIH R01 NS074057-01A1, Co-Investigator, 2011 ? 2017
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- Vera Bril, MD,
(2) CSL Behring (2) Baxalta (2) Grifols (2) Argenyx (2) Octapharma (2) Alpha Technologies (3) Powell Mansfield Inc (2) Shire (2) Akcea (2) UCB (2) Alnylam
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(2) CSL Behring
PLoS One, editorial board member starting 2016
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(2) CSL Behring, Grifols, Bionevia, Octapharma, Powell Mansfield Inc, Argenyx, Alpha Technologies, Baxalta, Akcea, UCB, Alnylam, Pfizer
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(2) CSL Behring, Grifols, Bionevia, Octapharma, Baxalta, ArgenX, UCB, Shire
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Toronto General/Toronto Western Hospital Foundation GBS/CIDP Foundation International
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- Ted M. Burns, MD,
Argenx, Momenta
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Argenx, Alexion Pharmaceuticals
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received support for consulting activities from UCB Pharma, CSL Behring, Momenta, Argenx
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- Renato Mantegazza, MD,
Dr. Mantegazza serves on a scientific advisory board for Alexion Pharmaceuticals and Biomarin
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(1) Alexion Pharmaceuticals Advisory Board (2) Biomarin Advisory Board (3) Argenx Advisory Board
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Italian Patent n.MI2011A 002106
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(1) Annual Funding for Research from the Italian Ministry of Health
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(1) AIM (Associazione Italiana per la lotta alla Miastenia)
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- Malgorzata Bilinska, MD,
Argenix, Novartis, Griffols, Beringer, Baxter.
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Argenix, Novartis, Griffols - funding for travel to Investigator Mitting; Beringer -EFNS 2018 and 2017.Baxter - Neurological congress in Krakow
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Argenix, Griffols, Novartis Signature: Małgorzata Bilinska Date: 29 Jan 2019
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- Andrzej Szczudlik, MD,
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Neurologia i Neurochirurgia Polska Editor in Chief, 2005 - present
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- Said Beydoun, MD,
Akcea, Alnylam, Alexion Pharmaceuticals, CSL, Grifols, Mitsubishi Tanabe, Shire
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US Neurology; Editor-in Chief, 2017-
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CSL, Grifols, Mitsubishi Tanabe, Alexion Pharmaceuticals, Shire
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Mallinkrodt, Pfizer, Catalyst, Argenx, UCB Pharma
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- Francisco Javier Rodriguez De Rivera Garrido, MD,
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- Fredrik Piehl, MD, PhD,
data safety monitoring committee Parexel/Chugai, outside of this study
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1. Biogen - unrestricted academic research projects outside of this study 2. Novartis - unrestricted academic research projects outside of this study 3. Genzyme - unrestricted academic research projects outside of this study 4. Merck KGaA - unrestricted academic research projects outside of this study
Swedish Medical Research Council (grant 2017-03054) PI, 2018- ongoing. Pcori, Washington DC (grant MS-1511-33196) PI, 2017- ongoing
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- Mariarosa Rottoli, MD,
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- Philip Van Damme, MD, PhD,
Served on the scientific advisory board of Biogen, Cytokinetcs, Sanofi, Pfizer, CSL Behring, Alexion Pharmaceuticals.
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Clinical research fellowship from FWO-Vlaanderen
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- Tuan Vu, MD,
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Allergan-Speaker bureau CSL Behring-Speaker bureau Alexion Pharmaceuticals-Speaker bureau MT Pharma-Speaker bureau
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Ipsen, commercial entity, consulting
Allergan (commercial) - nothing related to the study CSL Behring-Speaker bureau - Nothing related to the study Alexion Pharmaceuticals-Speaker bureau - nothing related to the study MT Pharma-Speaker bureau - nothing related to the study
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I participated in multicenter clinical trials as a site PI for Alexion Pharmaceuticals, Ra, UCB, Biogen, Flex, Grifols, Octapharma, Mallinkrodt, Orion, Cytokinetics, and ARGX
I participated in multicenter trials sponsored by NIH as a site PI: 5 R01 NS090083-05, 1 R21 HDO75327
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- Amelia Evoli, MD,
scientific advisory board - Alexion Pharmaceuticals data safety monitoring board - UCB
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Scientific award jury member for Grifols
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- Miriam Freimer, MD,
1.Advisory board- Alexion Pharmaceuticals 2. Advisory board- CSL Behring
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Alexinon- Have not given any talks
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1. Alexion Pharmaceuticals 2. UCB 3.Argenx 4. Immunovant 5. Alnylum 6.Amicus 7.Ra 8.Orphozyme 9.Acceleron 10. Catalyst 11. Grifols
NIH- neuronext
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Muscular Dystrophy Association clinic grant
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- Tahseen Mozaffar, MD,
On Medical and Scientific Advisory Board for the Myositis Association, Amicus, Biomarin, Genzyme, Idera Pharmaceuticals, and Ultragenyx
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Received travel reimbursement for advisory board meeting for 1) Genzyme Corporation; 2) Biomarin; and 3) Amicus
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1) Commercial or non-profit entity: Amicus, 2) Commercial or non-profit entity: Biomarin, 3) Commercial or non-profit entity: Genzyme, 4) Commercial or non-profit entity: Sarepta and 5) Commercial or non-profit entity: Ultragenyx 6) Commercial or non-profit entity: OptionCare 7) Commercial or non-profit entity: Spark Therapeutics
1) Commercial or non-profit entity: Genzyme Corporation 2) Commercial or non-profit entity: Grifols
received financial support from NuFACTOR, Inc. during the course of this study.
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1) Commercial or non-profit entity: Alnylam 2) Commercial or non-profit entity: Alexion Pharmaceuticals 3) Commercial or non-profit entity: Amicus 4) Commercial or non-profit entity: Biomarin 5) Commercial or non-profit entity: CSL Behring 6) Commercial or non-profit entity: Genzyme 7) Commercial or non-profit entity: Ionis 8) Commercial or non-profit entity: GSK 9) Commercial or non-profit entity: Novartis 10) Commercial or non-profit entity: Ultragenyx 11) Commercial or non-profit entity: Grifols 12) Commercial or non-profit entity: Octapharma
NIH Funding (primary investigator NS107210)
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- E. Sally Ward, PhD,
(1) Non-Profit - Therapeutic Antibody Core Scientific Advisory Board, Cancer Prevention and Research Institute of Texas (2015 - present) (2) Non-Profit - Scientific Advisory Board for Antibody Biology and Engineering, Gordon Research Conference (2017 - present)
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(1) Non-Profit - SELECTBIO, reimbursement (travel, hotel, meals) for March 2017 Advances in Drug Discovery conference (keynote speaker) (2) Non-Profit - GTCbio, reimbursement (travel, hotel, meals) for July 2017 5th Antibody and Protein Therapeutics conference (keynote speaker) (3) Commercial - argenx BVBA, reimbursement (travel, hotel, meals) for October 2017 meeting/presentation (speaker) (4) Non-Profit - Cancer Prevention and Research Institute of Texas, reimbursement (travel, hotel, meals) for November 2017 Therapeutic Antibody Core Symposium (keynote speaker) (5) Commercial - Cambridge Healthtech Institute, reimbursement (travel, hotel, meals) for January 2018 17th Annual PepTalk - Protein Science Week (invited speaker) (6) Non-Profit - Lupus Research Alliance, reimbursement (travel, hotel, meals) for January 2018 Human Immunology- Technology Initiative in Lupus (invited speaker) (7) Non-Profit - The Histochemical Society, reimbursement (travel, hotel, meals) for April 2018 Annual Meeting at Experimental Biology (invited speaker) (8) Commercial - Cambridge Healthtech Institute, reimbursement (travel, hotel, meals) for May 2018 PEGS 19th Annual Engineering Antibodies conference (keynote speaker) (9) Non-Profit - SELECTBIO, reimbursement (travel, hotel, meals) for May 2018 Stem Cells and Antibodies in Drug Discovery (invited speaker) (10) Non-Profit - Federation of American Societies for Experimental Biology, reimbursement (travel, hotel, meals) for June 2018 Immunoreceptors and Immunotherapy conference (primary organizer and speaker) (11) Non-Profit - Cancer Prevention and Research Institute of Texas, reimbursement (travel, hotel, meals) for November 2018 Therapeutic Antibody Core Symposium (invited speaker) (12) Non-Profit - The Antibody Society, reimbursement (travel, hotel, meals) for December 2018 Antibody Engineering & Therapeutics conference (keynote speaker) (13) Commercial - argenx BVBA, reimbursement (travel, hotel, meals) for January 2019 meeting
(1) Protein Engineering, Design and Selection (formerly Protein Engineering), Editorial Board member, 2003-present (2) The Antibody Society, Board of Distinguished Advisors member, 2009-present (3) mAbs, Editorial Board member, 2009-present
(1) (owned by UT Southwestern Medical Center) filed May 2006, Immunoglobulin Molecules With Improved Characteristics (2) (owned by UT Southwestern Medical Center and argenx BVBA) filed December 2014, FcRn Antagonists and Methods of Use E.S.W. is also a (co-)inventor on various patents that are not study-related from which she receives royalty payments through her previous employers (UT Southwestern Medical Center, U.K. Medical Research Council). E.S.W. has only partial knowledge of the licensing arrangements for these patents.
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E.S.W. has served as a consultant for various parties in the previous two years (contractual obligations do not permit public disclosure without prior consent from various parties).
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(1) Commercial - argenx BVBA Scientific Research Contract (2) Commercial - Bioverativ Scientific Research Contract (3) Commercial - Shire Pharmaceuticals Scientific Research Contract
(1) National Institutes of Health, R01 AR056478, Principal Investigator, August 2008 - May 2015 (2) National Institutes of Health, R01 GM085575, Co- Principal Investigator, August 2013 - present (3) Cancer Prevention and Research Institute of Texas, RP110441, Principal Investigator/Program Leader, July 2011 - December 2017 (4) Cancer Prevention and Research Institute of Texas, RP140141, Principal Investigator, August 2014 - present (5) Cancer Prevention and Research Institute of Texas, RP160051, Principal Investigator, March 2016 ? present
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(1) National Multiple Sclerosis Society (RG 2411) (2) Wellcome Trust (U.K.) Research grant
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E.S.W. is a (co-)inventor on various patents from which she receives royalty payments through her previous employers (UT Southwestern Medical Center, U.K. Medical Research Council). E.S.W. has only partial knowledge of the licensing arrangements for these patents.
(1) argenx BVBA
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E.S.W. has served as a consultant/expert witness in the previous two years (contractual obligations do not permit public disclosure without prior consent from various parties).
- Torsten Dreier, PhD,
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1) WO 2015/100299 Al human IgG1 derived Fc-fragment with ABDEG mutations and efficacy in murine ITP model. 2) WO 2018/083122 Al PK/PD data in cynomolgus monkeys and human volunteers
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CDO of argenx BVBA, the sponsor of the study described in manuscript
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- Peter Ulrichts, PhD,
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(1)FcRn antagonists and method of use (2) methods of reducing serum levels of fc-containing agents using fcrn antagonists (3)Chimeric human-llama antigens and methods of use (4)Antibodies to CD70 (5)Antibodies to complex targets
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argenx bvba, research fellow, 2010-current
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- Katrien Verschueren, MSc,
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argenx BVBA Since Sep 2017 Sr. Biostatistician
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- Antonio Guglietta, MD,
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I have been an employee of Argenx since Oct 2016. currently I am the VP of Clinical Development in this company
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As an employee of Argenx, I received stock options in the the following years: 2016, 2017 and 2018.
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- Hans de Haard, PhD,
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Named as inventor on patent 1) WO 2015/100299 A1 entitled
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Chief Scientific Officer and one of the three founders of the biotech company argenx BVBA (sponsor of the study described in the manuscript); have an employment at the company for more than 10 years (since July 2008). Get compensation in the form of salary and stock.
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As employee and Chief Scientific Officer of the sponsor argenx BVBA I was involved in writing the documents used for the interactions with FDA for the clinical study described in the manuscript.
- Nicolas Leupin, MD,
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argenx BVBA employee
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argenx BVBA employee, Chief Medical Officer
- Jan J.G.M. Verschuuren, MD, PhD;
Myasthenia Foundation of America (MGFA) medical/scientific advisory board. Study Steering Committee of Argenx. Advisory meeting for Rapharma. All reimbursements were received by the LUMC.
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Journal of Neuromuscular Diseases, member editorial board, 2014-now
Patents on MuSK myasthenia gravisE
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The Neurology department of the LUMC has received fees from Alexion Pharmaceuticals, Argen-X, and Rapharma because of consultancies
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Princes Beatrix Spierfonds, grant for MG research, Prinicpal investigator.
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Development of MuSK diagnostic antibody test for TECAN/IBL.
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- on behalf of the Efgartigimod MG Study Group
- From the Department of Neurology (J.F.H.), University of North Carolina, Chapel Hill; Krembil Neuroscience Centre (V.B.), University Health Network, Toronto, Canada; Department of Neurology (T.M.B.), University of Virginia, Charlottesville; Department of Neuroimmunology and Neuromuscular Diseases (R.M.), Fondazione Istituto Neurologico Carlo Besta, Milan, Italy; Department of Neurology (B.M.), Wroclaw Medical University; Department of Neurology (A.S.), Jagiellonian University Medical College, Cracow, Poland; Department of Neurology (S.B.), University of Southern California, Keck School of Medicine, Los Angeles County Medical Center; Department of Neurology (F.J.R.D.R.G.), La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Spain; Neuroimmunology Unit, Department Clinical Neuroscience (F.P.), Karolinska Institutet, Karolinska University Hospital (Solna), Stockholm, Sweden; USC Neurologia (M.R.), USS Malattie Autoimmuni–Centro Sclerosi Multipla, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; Neurology Department (P.V.D.), University Hospitals Leuven; Laboratory of Neurobiology (P.V.D.), Department of Neuroscience, KU Leuven and Center for Brain & Disease Research, VIB, Leuven, Belgium; Department of Neurology (T.V.), University of South Florida, Morsani College of Medicine, Tampa; Institute of Neurology (A.E.), Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; Neurology Department (M.F.), The Ohio State University, Columbus; Department of Neurology (T.M.), University of California, Irvine; Department of Molecular and Cellular Medicine (E.S.W.), Texas A&M University Health Science Center, College Station; argenx BVBA (T.D., P.U., K.V., A.G., H.d.H., N.L.), Zwijnaarde, Belgium; and Department of Neurology (J.J.G.M.V.), Leiden University Medical Center (LUMC), the Netherlands.
- Correspondence
Dr. Leupin nleupin{at}argenx.com
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