Drug for Alzheimer Disease Does Not Appear to Slow Cognitive Decline
CHICAGO, Dec. 15, 2009—Although there were promising results in a phase 2 trial, patients with mild Alzheimer disease who received the drug tarenflurbil as part of a phase 3 trial did not have better outcomes on measures of cognitive decline or loss of activities of daily living compared to patients who received placebo, according to a study in the December 16 issue of JAMA.
A leading theory on the pathophysiology of Alzheimer disease (AD) is the overproduction of amyloid-β (Aβ; a peptide of certain amino acids that appear to be the main constituent of amyloid plaques in the brains of patients with AD), particularly 42 amino acid peptide Aβ42. "Tarenflurbil, a selective Aβ42-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial," the authors write.
Robert C. Green, M.D., M.P.H., of the Boston University Schools of Medicine and Public Health, and colleagues conducted a large phase 3, randomized trial of tarenflurbil for patients with mild AD to determine its efficacy, safety and tolerability. The study, conducted at 133 trial sites in the United States, included 1,684 participants who were randomized, of whom 1,649 were included in the analysis, and 1,046 completed the 18-month trial. Patients were randomized to tarenflurbil, 800 mg, or placebo, administered twice a day.
The researchers found that tarenflurbil had no beneficial effect on the primary outcomes of cognition and activities of daily living after 18 months. There were also no significant differences on secondary outcomes, which included other AD assessment measures such as quality of life and caregiver burden.
Regarding adverse events, more participants taking tarenflurbil than those taking placebo experienced dizziness, upper respiratory tract infections and anemia.
"Our results are... a reminder that interventions affecting
amyloid have not yet been shown to alter the course of AD," the
(JAMA 2009;302:2557-2564. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
In an accompanying editorial, Thomas J. Montine, M.D., Ph.D., of the University of Washington, and Eric B. Larson, M.D., M.P.H., of the Group Health Research Institute, Seattle, comment on the findings of the two studies in this week's JAMA regarding dementia and Alzheimer disease.
"The null outcome for the leading ϒ-secretase modulator
[tarenflurbil] in a phase 3 trial and the surprisingly strong
association between plasma leptin and incident Alzheimer disease
underscore the need to broaden the current view of potential
therapeutic approaches to cognitive impairment and dementia in
older individuals. Research must seek a fuller understanding of the
complex convergence of Alzheimer disease with vascular disease and
Lewy body disease [a type of dementia], the application of
biomarkers and other surrogates to clinical trials to quantify
specific pharmacologic effects, and a multimodal approach to
prevention and treatment. Doing so could have profound effects on
the increasing numbers of older persons and on the societies
confronting the global challenge of late-life dementias in decades
(JAMA 2009;302:2593-2594. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
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Posted: December 2009