Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team.
Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development.
Critical Path Institute, Coalition Against Major Diseases, Tucson, AZ, USA.
Stephen P
SP
Arnerić
Roche Diagnostics, Basel, Switzerland.
Richard
R
Batrla-Utermann
University of California, Davis, CA, USA.
Laurel
L
Beckett
Roche Diagnostics, Basel, Switzerland.
Tobias
T
Bittner
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
Kaj
K
Blennow
AbbVie, Abbott Park, IL, USA.
Leslie
L
Carter
Eli Lilly and Company, Indianapolis, IN, USA.
Robert
R
Dean
Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
Sebastiaan
S
Engelborghs
AbbVie, Abbott Park, IL, USA.
Just
J
Genius
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
Mark Forrest
MF
Gordon
Eli Lilly and Company, Indianapolis, IN, USA.
Janice
J
Hitchcock
Eisai, Woodcliff Lake, NJ, USA.
June
J
Kaplow
Eisai, Woodcliff Lake, NJ, USA.
Johan
J
Luthman
Novartis, East Hanover, NJ, USA.
Richard
R
Meibach
Icon, Warrington, PA, USA.
David
D
Raunig
Critical Path Institute, Coalition Against Major Diseases, Tucson, AZ, USA.
Klaus
K
Romero
Janssen R&D, Raritan, NJ, USA.
Mahesh N
MN
Samtani
Merck, Rahway, NJ, USA.
Mary
M
Savage
University of Pennsylvania, Philadelphia, PA, USA.
Leslie
L
Shaw
Critical Path Institute, Coalition Against Major Diseases, Tucson, AZ, USA.
Diane
D
Stephenson
Meso Scale Diagnostics, LLC, Rockville, MD, USA.
Robert M
RM
Umek
Biomarkable, Gent, Belgium.
Hugo
H
Vanderstichele
Eli Lilly and Company, Indianapolis, IN, USA.
Brian
B
Willis
Genentech/Roche, San Francisco, CA, USA.
Susan
S
Yule
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D055808:Drug Discovery; D006801:Humans
D015415:Biomarkers
Alzheimer’s disease; Coalition Against Major Diseases; biomarker qualification; cerebrospinal fluid biomarkers
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