Journal
NEUROLOGY
Volume 77, Issue 13, Pages 1253-1262Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182309fa5
Keywords
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Funding
- Elan Corporation
- Janssen Alzheimer's Immunotherapy
- Bayer Schering Pharma
- Wyeth
- Bristol-Myers Squibb
- Pfizer Inc
- Eisai Inc.
- Myriad Genetics, Inc.
- GlaxoSmithKline
- Neurochem-Alzhemed
- Cephalon, Inc.
- Forest Laboratories Inc.
- Voyager
- NIH/NIA
- Norman and Rosalie Fain Family Foundation
- Champlin Foundation
- John and Happy White Foundation
- Janssen
- Alzheimer's Association
- American Health Assistance Foundation
- Anonymous Foundation
- Avid Radiopharmaceuticals, Inc
- Novartis
- Baxter International Inc.
- Janssen AI
- Medivation, Inc.
- Toyama Chemical Co., Ltd.
- Eli Lilly and Company
- Forest Laboratories, Inc.
- Merck Serono
- Mitsubishi Tanabe Pharma Corporation
- Neurochem Inc
- Ono Pharmaceutical Co. Ltd.
- NIH (NIA, NIMH)
- Abbott
- Sanofi-Synthelabo Research
- National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD)
- Shire plc
- Kavli Neuroscience Institute at Yale
- NARSAD
- Johnson Johnson
- Biogen Idec
- Canadian Institutes of Health Research
- Multiple Sclerosis Society of Canada
- NIH/NINDS
- GE Healthcare
- Arizona Department of Healt
- Toyama Chemical, Co., Ltd.
- Takeda Pharmaceutical Company Limited
- AstraZeneca
- Avid Radiopharmaceuticals, Inc.
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Objective: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). Methods: A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n = 84) to placebo (n = 82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. Results: The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p = 0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF A beta x-42 was decreased significantly compared to placebo (p = 0.009). Conclusions: Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. Classification of evidence: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005. Neurology (R) 2011; 77: 1253-1262
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