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TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease
Salloway S, Pain A, Lee E, Papka M, Ferguson MB, Wang H, Hu H, Lu M et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-05-01
Topic: Drug trials: efficacy and safety
Introduction The phase 3, open-label TRAILBLAZER-ALZ 4 study compared the effect of donanemab versus aducanumab on amyloid plaque (AP) clearance in participants with early symptomatic Alzheimer's disease. Methods Participants (n = 148) were randomized 1:1 to receive intravenous donanemab (700 mg every 4 weeks for three doses, then 1400 mg every 4 weeks thereafter) or aducanumab (per label). AP was measured with florbetapir F 18 positron emission tomography. AP clearance was defined as < 24.1 Centiloids. Results At 6, 12, and 18 months, AP clearance was achieved in 37.9%, 70.0%, and 76.8%, respectively, of donanemab-treated participants versus 1.6%, 24.6%, and 43.1% of aducanumab-treated participants (P < 0.001). Median time to clearance was 359 versus 568 days for donanemab- versus aducanumab-treated participants (P < 0.001). Amyloid-related imaging abnormality (ARIA)-edema/effusion occurred in 23.9% and 34.8% of donanemab- and aducanumab-treated participants, respectively. Discussion Donanemab treatment resulted in earlier and greater AP clearance compared to aducanumab. ARIA frequencies were consistent with prior studies. Clinical trial registration No: NCT05108922, TRAILBLAZER-ALZ 4 HIGHLIGHTS: Here we report the first direct comparator study of two amyloid-targeting therapies. This was the first investigation of donanemab on biomarker efficacy regardless of tau levels. Donanemab demonstrated superiority over aducanumab in amyloid plaque (AP) clearance. The depth and speed of AP removal did not affect amyloid-related imaging abnormality risk or incidence.
Key findings
- Introduction The phase 3, open-label TRAILBLAZER-ALZ 4 study compared the effect of donanemab versus aducanumab on amyloid plaque (AP) clearance in participants with early symptomatic Alzheimer's disease.
- Results At 6, 12, and 18 months, AP clearance was achieved in 37.9%, 70.0%, and 76.8%, respectively, of donanemab-treated participants versus 1.6%, 24.6%, and 43.1% of aducanumab-treated participants (P < 0.001).
- Median time to clearance was 359 versus 568 days for donanemab- versus aducanumab-treated participants (P < 0.001).
- Discussion Donanemab treatment resulted in earlier and greater AP clearance compared to aducanumab.
- Donanemab demonstrated superiority over aducanumab in amyloid plaque (AP) clearance.
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Study details
- Study designclinical trial
- Participants148
- Effect size37.9%; 70.0%; 76.8%
- Evidence strengthHigh
How this study scored 88/100
Published in a leading specialty journal, and it is a large phase 3 trial. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 51 of the 58 points we could judge it on, which is 88 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 148 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40390253) |
| Free to read | 2 / 2 | Free to read |
| Points | 51 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 51 of the 58 points we could judge it on is 88 out of 100. |
| Total | 88 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Salloway, S., Pain, A., Lee, E., Papka, M., Ferguson, M. B., Wang, H., et al. (2025). TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70293
Vancouver
Salloway S, Pain A, Lee E, Papka M, Ferguson MB, Wang H, et al. TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70293. PMID: 40390253.
BibTeX
@article{salloway2025-40390253,
author = {Salloway, S. and Pain, A. and Lee, E. and Papka, M. and Ferguson, M. B. and Wang, H. and Hu, H. and Lu, M. and others},
title = {{TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70293},
pmid = {40390253},
url = {https://doi.org/10.1002/alz.70293}
}
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