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Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial
Randall J Bateman, Yan Li, Eric M McDade, Jorge J Llibre-Guerra, David B Clifford, Alireza Atri, Susan L Mills, Anna M Santacruz et al.. The Lancet. Neurology, 2025-04
Topic: Drug trials: efficacy and safety
Of 74 participants who were recruited into the OLE study between June 3, 2020, and April 22, 2021, 73 were enrolled and received gantenerumab treatment. 47 (64%) stopped dosing due to early termination of the study by the sponsor, and 13 (18%) prematurely discontinued the study for other reasons; 13 people completed 3 years of treatment. The mITT group for the primary analysis comprised 55 participants. At the interim analysis, the hazard ratio for clinical decline of CDR-SB in asymptomatic mutation carriers was 0·79 (n=53 [95% CI 0·47 to 1·32]) for participants who were treated with gantenerumab in either the double-blind or OLE period (Any Gant), and 0·53 (n=22 [0·27 to 1·03]) for participants who were treated with gantenerumab the longest (Longest Gant). At the final analysis, the adjusted mean change from OLE baseline to year 3 in PiB-PET SUVR was -0·71 SUVR (95% CI -0·88 to -0·53, p<0·0001). Amyloid-related imaging abnormalities occurred in 53% (39 of 73) of Partial or short-term amyloid removal did not show significant clinical effects. However, long-term full amyloid removal potentially delayed symptom onset and dementia progression. Our conclusions are limited due to the OLE design and use of external controls and need to be confirmed in long-term trials. FUNDING: National Institute on Aging, Alzheimer's Association, GHR Foundation, and F Hoffmann-La Roche/Genentech.
Key findings
- Of 74 participants who were recruited into the OLE study between June 3, 2020, and April 22, 2021, 73 were enrolled and received gantenerumab treatment. 47 (64%) stopped dosing due to early termination of the study by the sponsor, and 13 (18%) prematurely discontinued the study for other reasons; 13 people completed 3 years of treatment.
- The mITT group for the primary analysis comprised 55 participants.
- At the interim analysis, the hazard ratio for clinical decline of CDR-SB in asymptomatic mutation carriers was 0·79 (n=53 [95% CI 0·47 to 1·32]) for participants who were treated with gantenerumab in either the double-blind or OLE period (Any Gant), and 0·53 (n=22 [0·27 to 1·03]) for participants who were treated with gantenerumab the longest (Longest Gant).
- At the final analysis, the adjusted mean change from OLE baseline to year 3 in PiB-PET SUVR was -0·71 SUVR (95% CI -0·88 to -0·53, p<0·0001).
- Amyloid-related imaging abnormalities occurred in 53% (39 of 73) of Partial or short-term amyloid removal did not show significant clinical effects.
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Study details
- Study designclinical trial
- Participants53
- Evidence strengthHigh
How this study scored 83/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. 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 free to read, so those were left out: it earned 49 of the 59 points we could judge it on, which is 83 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Lancet. Neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 1 / 4 | 53 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (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 | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40120616) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 49 / 59 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 49 of the 59 points we could judge it on is 83 out of 100. |
| Total | 83 / 100 | — |
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Bateman, R. J., Li, Y., McDade, E. M., Llibre-Guerra, J. J., Clifford, D. B., Atri, A., et al. (2025). Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(25)00024-9
Vancouver
Bateman RJ, Li Y, McDade EM, Llibre-Guerra JJ, Clifford DB, Atri A, et al. Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial. The Lancet. Neurology. 2025. doi:10.1016/s1474-4422(25)00024-9. PMID: 40120616.
BibTeX
@article{bateman2025-40120616,
author = {Bateman, Randall J and Li, Yan and McDade, Eric M and Llibre-Guerra, Jorge J and Clifford, David B and Atri, Alireza and Mills, Susan L and Santacruz, Anna M and others},
title = {{Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial}},
journal = {The Lancet. Neurology},
year = {2025},
doi = {10.1016/s1474-4422(25)00024-9},
pmid = {40120616},
url = {https://doi.org/10.1016/s1474-4422(25)00024-9}
}
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