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Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Rachelle Smith Doody, Ronald G. Thomas, Martin Rhys Farlow, Takeshi Iwatsubo, Bruno J. Vellas, Steven Joffe, Karl D. Kieburtz, Rema Raman, Xiaoying Sun, Paul S. S. Aisen, Eric Siemers, Hong Liu‐Seifert, Richard C. Mohs. New England Journal of Medicine, 2014-01-22
Topic: Amyloid, tau and blood-test diagnosis
BACKGROUND: Alzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain. METHODS: In two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we randomly assigned 1012 and 1040 patients, respectively, with mild-to-moderate Alzheimer's disease to receive placebo or solanezumab (administered intravenously at a dose of 400 mg) every 4 weeks for 18 months. The primary outcomes were the changes from baseline to week 80 in scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11; range, 0 to 70, with higher scores indicating greater cognitive impairment) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL; range, 0 to 78, with lower scores indicating worse functioning). After analysis of data from EXPEDITION 1, the primary outcome for EXPEDITION 2 was revised to the change in scores on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; range, 0 to 90, with higher scores indicating greater impairment), in patients with mild Alzheimer's disease. RESULTS: Neither study showed significant improvement in the primary outcomes. The modeled difference between groups (solanezumab group minus placebo group) in the change from baseline was -0.8 points for the ADAS-cog11 score (95% confidence interval [CI], -2.1 to 0.5; P=0.24) and -0.4 points for the ADCS-ADL score (95% CI, -2.3 to 1.4; P=0.64) in EXPEDITION 1 and -1.3 points (95% CI, -2.5 to 0.3; P=0.06) and 1.6 points (95% CI, -0.2 to 3.3; P=0.08), respectively, in EXPEDITION 2. Between-group differences in the changes in the ADAS-cog14 score were -1.7 points in patients with mild Alzheimer's disease (95% CI, -3.5 to 0.1; P=0.06) and -1.5 in patients with moderate Alzheimer's disease (95% CI, -4.1 to 1.1; P=0.26). In the combined safety data set, the incidence of amyloid-related imaging abnormalities with edema or hemorrhage was 0.9% with solanezumab and 0.4% with placebo for edema (P=0.27) and 4.9% and 5.6%, respectively, for hemorrhage (P=0.49). CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. (Funded by Eli Lilly; EXPEDITION 1 and 2 ClinicalTrials.gov numbers, NCT00905372 and NCT00904683.).
Why it matters
Two phase 3 trials (EXPEDITION 1 and 2) randomly assigned 1012 and 1040 people with mild-to-moderate Alzheimer's disease to solanezumab, an antibody that binds amyloid, or placebo every 4 weeks for 18 months. Neither trial showed significant improvement in the primary outcomes, and the authors conclude solanezumab failed to improve cognition or functional ability.
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How this study scored 62/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported and studied in people because the record does not state it. We have no data on strength of evidence, so that was left out: it earned 59 of the 95 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (New England Journal of Medicine) |
| Journal's citation record | 4 / 4 | New England Journal of Medicine: journal h-index 1,505 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 7 / 7 | Cited 1,668 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 119.1 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 6 / 6 | Cited 124.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 4 / 4 | Cited 253 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Richard C. Mohs: h-index 75 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24450890) |
| Free to read | 2 / 2 | Free to read |
| Points | 59 / 95 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 95 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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Read the original
- DOI: 10.1056/nejmoa1312889
- PubMed: 24450890
- Original source →
- Free full text: New England Journal of Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 13 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Doody, R. S., Thomas, R. G., Farlow, M. R., Iwatsubo, T., Vellas, B. J., Joffe, S., et al. (2014). Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1312889
Vancouver
Doody RS, Thomas RG, Farlow MR, Iwatsubo T, Vellas BJ, Joffe S, et al. Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease. New England Journal of Medicine. 2014. doi:10.1056/nejmoa1312889. PMID: 24450890.
BibTeX
@article{doody2014-24450890,
author = {Doody, Rachelle Smith and Thomas, Ronald G. and Farlow, Martin Rhys and Iwatsubo, Takeshi and Vellas, Bruno J. and Joffe, Steven and Kieburtz, Karl D. and Raman, Rema and Sun, Xiaoying and Aisen, Paul S. S. and Siemers, Eric and Liu‐Seifert, Hong and Mohs, Richard C.},
title = {{Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease}},
journal = {New England Journal of Medicine},
year = {2014},
doi = {10.1056/nejmoa1312889},
pmid = {24450890},
url = {https://doi.org/10.1056/nejmoa1312889}
}
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