Conflict of interest statement: S. Paganoni reports grants from Amylyx 
Pharmaceuticals, Inc, The ALS Association, and ALS Finding A Cure during the 
conduct of the study, and grants from Revalesio, Ra Pharma, Biohaven, Clene 
Nanomedicine, and Prilenia, outside the submitted work. S. Hendrix reports other 
personal fees from Pentara Corporation, outside the submitted work. S.P. Dickson 
reports other personal fees from Pentara outside the submitted work. E.A. 
Macklin reports grants from Amylyx, The ALS Association, and ALS Finding A Cure 
Foundation during the conduct of the study. He is also a data and safety 
monitoring board member (DSMB) and reports grants from Acorda Therapeutics; 
steering committee membership for Biogen; consultant work for Cerevance; grants 
from GlaxoSmithKline; consultant work for Inventram, Lavin Consulting, and 
Myolex; grants from Mitsubishi Tanabe Pharmaceuticals; and DSMB membership for 
Novartis Pharmaceuticals and Shire Human Genetic Therapies, outside the 
submitted work. J.D. Berry reports grants from ALS Finding A Cure, The ALS 
Association, and Amylyx during the conduct of the study; personal fees from 
Biogen and Clene Nanomedicine; and grants from Alexion, Biogen, MT Pharma of 
America, Anelixis Therapeutics, Brainstorm Cell Therapeutics, Genentech, nQ 
Medical, National Institute of Neurological Disorders and Stroke, and the 
Muscular Dystrophy Association, outside the submitted work. M.A. Elliott has 
received personal fees from Amylyx and personal fees from Biogen. C. Karam 
reports grants and personal fees from Akcea, Alnylam, and Genzyme, and personal 
fees from Acceleron, Biogen, Alexion, Argenx, Cytokinetics, and CSL Behring, 
outside the submitted work. J.B. Caress reports grants from Amylyx during the 
conduct of the study, and grants from Orion Pharmaceuticals, MTB Pharma, and 
Cytokinetics, outside the submitted work. J. Wymer reports grants from Amylyx 
during the conduct of the study. S.A. Goutman reports grants from The ALS 
Association during the conduct of the study; grants from the National Institutes 
of Health/National Institutes of Environmental Health Sciences, The ALS 
Association, and Target ALS, outside the submitted work; consultant work for 
Biogen and ITF Pharma, outside the submitted work; and personal fees from 
Biogen, ITF Pharma, Watermark Research Partners, and for expert testimony, 
outside the submitted work. T.D. Heiman‐Patterson reports grants from Mitsubishi 
Tanabe Pharma America, Amylyx Pharmaceuticals, The ALS Association, and Orion 
Pharma, and personal fees from Cytokinetics, ITF, and Biohaven, outside the 
submitted work. C.E. Jackson reports grants from Amylyx during the conduct of 
the study; grants and personal fees from Cytokinetics, personal fees from CSL 
Behring, grants and personal fees from Mitsubishi Tanabe Pharma America, DSMB 
membership, and personal fees from Brainstorm and Mallinckrodt during the 
conduct of this study; and personal fees from ITF Pharma, outside the submitted 
work. C. Quinn received personal fees for serving on an advisory board of 
Amylyx, outside the submitted work. J.D. Rothstein reports licensing agreement 
and nonfinancial support from Ionis Pharmaceuticals; nonfinancial support from 
Calico, Biogen, and IBM Watson; research grant support from the National 
Institute of Neurological Disorders and Stroke, National Institute on Aging, 
Department of Defense, the Chan Zuckerberg Initiative, Microsoft, The ALS 
Association, the Muscular Dystrophy Association, Target ALS, F Prime, ALS 
Finding A Cure, Answer ALS, Robert Packard Center for ALS Research, 
GlaxoSmithKline, Travelers Insurance, American Airlines, Caterpillar, and the 
National Football League; and personal consulting fees from Expansion 
Therapeutics and Team Gleason. He also reports that his institution was a trial 
site and thus had a contract with Amylyx to participate in the study. J. Katz 
reports personal fees from MT Pharma America, Denali Pharmaceuticals, Genentech, 
and Calico, outside the submitted work. S. Ladha reports grants from Amylyx, 
Biogen, and MT Pharma, and personal fees from Amylyx and Biogen. T.M. Miller 
reports licensing agreement and nonfinancial support from Ionis Pharmaceuticals, 
a licensing agreement with C2N, grants and personal fees from Biogen, and 
personal fees from Cytokinetics and Disarm Therapeutics, outside the submitted 
work. S.N. Scelsa reports grants from Amylyx during the conduct of the study, 
and grants from Orion Pharma, outside the submitted work. T.H. Vu reports 
personal fees from the speakers bureau of Mitsubishi Tanabe Pharmaceuticals, and 
has participated in clinical trials sponsored by Amylyx, Orion, Biogen, 
Mallinckrodt, and Cytokinetics during the conduct of the study. J.D. Glass 
reports that his institution was a trial site and thus had a contract from 
Amylyx to participate in the study. A. Swenson reports research support from 
Amylyx, The ALS Association, Massachusetts General Hospital, the National 
Institutes of Health/National Institute of Neurological Disorders and Stroke, 
and serving on an independent data monitoring committee for Alexion. P.L. Andres 
reports personal fees from Amylyx for consulting during the conduct of the study 
and has an isometric strength testing apparatus (US Patent 7493812B2) held by 
the Hospital Corporation. S. Babu reports research support from the American 
Academy of Neurology, the AANEM Foundation, The ALS Association, the Muscular 
Dystrophy Association, Biogen, Orion, Voyager Therapeutics, and Novartis. M. 
Chase reports grants to the Massachusetts General Hospital (MGH) from The ALS 
Association, grants to the MGH from ALS Finding A Cure, and fee for service from 
Amylyx during the conduct of the study. M. Hall reports grants for funding for 
clinical trial monitoring and outcomes training support from The ALS Association 
and Amylyx during the conduct of the study. G. Kittle reports grants from The 
ALS Association and Amylyx during the conduct of the study. J.M. Shefner reports 
grants and personal fees from Amylyx during the conduct of the study; personal 
fees for consulting work from Cytokinetics and Brainstorm; grants and personal 
fees for outcomes training and study design from Mitsubishi Pharma America, 
outside the submitted work; personal fees for consulting from Neurosense and 
Otsuka, outside the submitted work; and grants for outcomes training from 
Alexion, Medicinova, and Biogen, outside the submitted work. He is also 
Neuromuscular section editor for UpToDate. J. Wittes and Z.‐F. Yu report 
payments from Amylyx to their employer during the conduct of the study. J. Cohen 
and J. Klee report a relationship with Amylyx during the conduct of the study, 
and they serve as co‐CEOs of Amylyx, outside the submitted work, with multiple 
patents issued to Amylyx. K. Leslie reports being full‐time employee of Amylyx 
during the conduct of the study, and personal fees from Amylyx, outside the 
submitted work. R.E. Tanzi reports personal fees from Amylyx outside the 
submitted work; has helped with inception and design of the clinical trial but 
was not involved with running the trial and had no contact with the trial 
subjects; and owns founding equity in Amylyx and serves as head of the company's 
scientific advisory board. W. Gilbert was director of Amylyx during the conduct 
of the study and a company shareholder. P.D. Yeramian reports full‐time 
employment at Amylyx during the conduct of the study. D. Schoenfeld reports 
grants from The ALS Association, during the conduct of the study, and personal 
fees from Immunitypharma and Alexion, outside the submitted work. M.E. Cudkowicz 
reports grants from Massachusetts General Hospital during the conduct of the 
study; grants from Clene Nanomedicine, Ra Pharma, Biohaven, and Prilenia, 
outside the submitted work; and personal fees from Takeda, Biogen, Sunovian, 
Cytokinetics, and Immunity Pharma, outside the submitted work. The remaining 
authors declare no potential conflicts of interest.