Abstract
There have been some successes in qualifying biomarkers and applying them to drug development and clinical treatment of various diseases. A recent success is illustrated by a collaborative effort among the US Food and Drug Administration, the European Medicines Agency, and the pharmaceutical industry to provide a set of seven preclinical kidney toxicity biomarkers for drug development. Other successes include, but are not limited to, clinical biomarkers for cancer treatment and clinical management of heart transplant patients. The value of fully qualified surrogate endpoints in facilitating successful drug development is undisputed, especially for diseases in which the traditional clinical outcome can only be assessed in large, multi-year trials. Emerging biomarkers, including chemical genomic or imaging biomarkers, and measurement of circulating tumor cells hold great promise for early diagnosis of disease and as prognostic tests for managing treatment of chronic diseases such as osteoarthritis, Alzheimer disease, cardiovascular disease, and cancer. To advance the success of treating and managing these diseases, efforts are needed to establish the temporal relationship between changes in inflammatory or imaging biomarkers with the progression of the chronic disease, and in the case of cancer, between the extent of circulating cancer cells and tumor progression or remission.
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References
EvaluatePharma. FDA website (PDUFA).
VXDS. http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/ucm073575.pdf. accessed Aug. 2010.
BQ. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174433.pdf. accessed Aug, 2010.
http://www.emea.europa.eu/pdfs/human/biomarkers/7289408en.pdf.
PSTC. http://www.c-path.org/pstc.cfm The PSTC is a unique public-private partnership, led by the non-profit Critical Path Institute (C-Path), that brings together pharmaceutical companies to share and validate each other’s safety testing methods under advisement of the Food and Drug Administration (“FDA”) and its European counterpart. accessed July 2010.
Wagner JA. Strategic approach to fit-for-purpose biomarkers in drug development. Annu Rev Pharmacol Toxicol. 2008;48:631–51.
Wagner JA, Williams SA, Webster CJ. Biomarkers and surrogate end points for fit-for-purpose development and regulatory evaluation of new drugs. Clin Pharmacol Ther. 2007;81(1):104–7.
Wagner JA, Wright EC, Ennis MM, Prince M, Kochan J, Nunez DJ, et al. Utility of adiponectin as a biomarker predictive of glycemic efficacy is demonstrated by collaborative pooling of data from clinical trials conducted by multiple sponsors. Clin Pharmacol Ther. 2009;86(6):619–25.
Burckart GJ, Amur S. Update on the clinical pharmacogenomics of organ transplantation. Pharmacogenomics. 2010;11(2):227–36.
Bernstein D, Williams GE, Eisen H, Mital S, Wohlgemuth JG, Klingler TM, et al. Gene expression profiling distinguishes a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients. J Heart Lung Transplant. 2007;26(12):1270–80.
Lievre A, Laurent-Puig P. Genetics: Predictive value of KRAS mutations in chemoresistant CRC. Nat Rev Clin Oncol. 2009;6(6):306–7.
Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34.
Yao Z, Hoffman EP, Ghimbovschi S, Dubois DC, Almon RR, Jusko WJ. Mathematical modeling of corticosteroid pharmacogenomics in rat muscle following acute and chronic methylprednisolone dosing. Mol Pharm. 2008;5(2):328–39.
Earp JC, Dubois DC, Molano DS, Pyszczynski NA, Almon RR, Jusko WJ. Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis. J Pharmacol Exp Ther. 2008;326(2):546–54.
Tavora FR, Ripple M, Li L, Burke AP. Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques. BMC Cardiovasc Disord. 2009;9:27.
Burstein D. MRI for development of disease-modifying osteoarthritis drugs. NMR Biomed. 2006;19(6):669–80.
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009;302(4):385–93.
Blennow K, Vanmechelen E, Hampel H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer’s disease. Mol Neurobiol. 2001;24(1–3):87–97.
Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007;64(3):343–9.
Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2(10):605–13.
Frisoni GB, Lorenzi M, Caroli A, Kemppainen N, Nagren K, Rinne JO. In vivo mapping of amyloid toxicity in Alzheimer disease. Neurology. 2009;72(17):1504–11.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group. N Engl J Med. 1999;340(1):14–22.
Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet. 2001;357(9256):577–81.
Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431–43.
Niizuma K, Shimizu H, Takada S, Tominaga T. Middle cerebral artery plaque imaging using 3-Tesla high-resolution MRI. J Clin Neurosci. 2008;15(10):1137–41.
Hayes DF, Smerage J. Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res. 2008;14(12):3646–50.
Smerage JB, Hayes DF. The prognostic implications of circulating tumor cells in patients with breast cancer. Cancer Investig. 2008;26(2):109–14.
SWOG-S0500. http://www.cancer.gov/clinicaltrials/SWOG-S0500. accessed August, 2010.
Acknowledgment
The authors, who are members of the organizing committee for the meeting, thank the American Association of Clinical Pharmacology and the American Association of Pharmaceutical Scientists and their staff for their support. We also acknowledge Drs. B. Joy Snider, Erik S.G. Stroes, Jacky Vonderscher, and Issam Zineh who presented at the workshop but did not participate in this proceeding.
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The views expressed in this article by the FDA employees do not necessarily represent the views of the US Food and Drug Administration.
An erratum to this article can be found at http://dx.doi.org/10.1208/s12248-011-9275-8
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Bai, J.P.F., Bell, R., Buckman, S. et al. Translational Biomarkers: from Preclinical to Clinical a Report of 2009 AAPS/ACCP Biomarker Workshop. AAPS J 13, 274–283 (2011). https://doi.org/10.1208/s12248-011-9265-x
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DOI: https://doi.org/10.1208/s12248-011-9265-x