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A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Open accessAbstract
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 Aβx-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.
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“The oral drug, scyllo-inositol is a Aβ42 aggregation inhibitor that was studied in AD subjects (ELND005). A clinical study (phase 2) in patients with AD found no confirmation of ELND005′s clinical benefit, and the study was stopped due to severe toxicity concerns (Salloway et al., 2011).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Salloway et al., 2011
In the citing paper
“Further development of the agent at a lower dose has not progressed in the last 8 years.50”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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“A phase 2 clinical trial in patients with AD did not provide evidence to support a clinical benefit of ELND005 while severe toxicity issues (infections) forced the cessation of the study.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
In the citing paper
“The last Aβ42 aggregation inhibitor which was tested in humans was the oral agent scyllo-inositol (ELND005).”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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“Aggregation inhibitors such as scyllo-inositol did not meet primary efficacy endpoints in phase 2 (Salloway et al., 2011).”
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Metadata
- Authors
- Salloway, S., Sperling, R., Keren, R., Porsteinsson, A. P., van Dyck, C. H., Tariot, P. N., Gilman, S., Arnold, D., Abushakra, S., Hernandez, C., Crans, G., Liang, E., Quinn, G., Bairu, M., Pastrak, A., Cedarbaum, J. M., & For the ELND005-AD201 Investigators
- Affiliations
- Brigham and Women's Hospital (US)
- From the Department of Neurology, Butler Hospital, and Department of Neurology, Alpert Medical School of Brown University (S.S.), Providence, RI; Center for Alzheimer Research and Treatment (R.S.), Brigham and Women's Hospital, Boston, MA; Ontario Shores Centre for Mental Health Sciences (R.K.), Whitby, Canada; Monroe Community Hospital (A.P.P.), University of Rochester Medical Center, Rochester, NY; Departments of Psychiatry and Neurobiology (C.H.v.D.), Yale University School of Medicine, New Haven...
- ORCID
- Venue
- Neurology
- Published
- 2011-09-27
- Volume
- 77
- Issue
- 13
- Pages
- 1253-1262
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3179648
- OpenAlex
- W2119197968
- Cited by
- 258
- References
- 42
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 18 · 2021: 14 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 20 · 2016: 22 · 2015: 21 · 2014: 21 · 2013: 24 · 2012: 17
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Elan
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- scyllo-inositol, Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, activities of daily living, neuropsychological performance, dose-ranging, drug safety
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Alzheimer Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Inositol, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Peptide Fragments, Platelet Aggregation Inhibitors, Time Factors, Amyloid beta-Peptides, Treatment Outcome, Apolipoprotein E4
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