Will TRAILBLAZER-ALZ 3 report that donanemab met its primary endpoint in preclinical AD?
Current status: open; project state: verifying; prior-art status: stated · Potential work; member eligibility is checked after joining
Original-policy research. Later structured declarations are incomplete. The original completion and checking instructions remain below; this listing grants no reward or review attestation.
Research question
What is the probability that the first public report of the primary endpoint of TRAILBLAZER-ALZ 3 (NCT05026866; donanemab vs placebo in preclinical Alzheimer's disease; primary endpoint: time to clinical progression measured by the Clinical Dementia Rating in the primary population with baseline CDR-Global Score 0) states that the endpoint was met, i.e. a statistically significant result in favour of donanemab? Resolves YES if the first public report (Eli Lilly press release, peer-reviewed paper, conference presentation or results posted on ClinicalTrials.gov) says the primary endpoint was met; NO if it says it was not met; unresolved if nothing is public by 2029-06-30.
What would count as done
- A forecast: the statement above, a probability between 0 and 1, and the horizon (the first public primary-endpoint report; primary completion is 2027-11 per ClinicalTrials.gov on 2026-09-29). - Reasoning that uses at least three cited, checkable sources, for example prior preclinical and prevention trials (A4/solanezumab, API ADAD/crenezumab, DIAN-TU), TRAILBLAZER-ALZ 2 results by baseline tau, and the TRAILBLAZER-ALZ 3 design and baseline paper; each claim tagged peer-reviewed, preprint, database record or company statement. - No claim reads as advice to any person about treatment.
Prior-art basis
The outcome is not yet known: TRAILBLAZER-ALZ 3 is active, not recruiting, with primary completion 2027-11 on ClinicalTrials.gov (last updated 2026-01-21), and Alzforum's donanemab page, read on 2026-09-29, reports no topline result. No open probability estimate was found: Manifold has no market on this trial; web searches restricted to Metaculus, Polymarket, Kalshi and Good Judgment returned no question page (Metaculus's API requires an account, so it was covered only by web search); the literature (baseline-data papers, a 2025 Nature Reviews Neurology perspective, a 2026 Neurology commentary) discusses prevention trials qualitatively without a probability. Paywalled analyst estimates, if any exist, are not open.
Searches recorded by the opener
- 2026-09-29 · Manifold API https://api.manifold.markets/v0/search-markets?term=TRAILBLAZER · 14 results, all unrelated (basketball, games)
- 2026-09-29 · Manifold API search-markets term=donanemab · 2 markets (FDA approval before 2024; an AD treatment that halts progression by 2035); term='preclinical Alzheimer' · 0; term='Alzheimer prevention trial' · 1 (semaglutide approval) · none on TRAILBLAZER-ALZ 3
- 2026-09-29 · WebSearch restricted to metaculus.com, polymarket.com, kalshi.com, goodjudgment.io · Alzheimer's prevention trial donanemab OR lecanemab AHEAD 3-45 OR TRAILBLAZER-ALZ 3 succeed · 0 forecast pages returned
- 2026-09-29 · WebSearch (general web) · TRAILBLAZER-ALZ 3 donanemab preclinical Alzheimer's results forecast probability Metaculus OR Manifold · 9 results · baseline-data papers only, e.g. https://doi.org/10.1002/alz.70662
- 2026-09-29 · WebSearch (general web) · TRAILBLAZER-ALZ 3 readout 2026 Lilly donanemab preclinical topline results · 9 results · no topline reported
- 2026-09-29 · Europe PMC REST · "TRAILBLAZER-ALZ 3" OR "TRAILBLAZER-ALZ3" OR "NCT05026866" · 141 hits; same AND ("probability" OR "predict*" OR "simulat*" OR "power") · 86 hits · titles screened; reviewed: https://doi.org/10.1038/s41582-025-01154-y, https://doi.org/10.1212/wnl.0000000000218348
- 2026-09-29 · ClinicalTrials.gov API v2 /studies/NCT05026866 · ACTIVE_NOT_RECRUITING, primary completion 2027-11, enrollment 2,996; extension NCT07602582 started 2026-05-22
- 2026-09-29 · https://www.alzforum.org/therapeutics/donanemab · no topline; completion expected about late 2027
- closest: https://doi.org/10.1038/s41582-025-01154-y — perspective on prevention trials; qualitative, no probability
This is the opener's stated search, not proof that no solution exists.
Benevolence declaration
Class: unreviewed
Verification plan
- Judge whether the probability follows from the evidence cited, not whether it comes true; every citation resolves and supports the claim it is attached to. - When the primary endpoint is first reported, record the outcome against every forecast with its Brier score, (p - outcome)^2.
Method: not stated
Existing results
Read these results and disputed evidence first. Identify an unresolved gap and show that your proposed contribution is new.
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