- Design
- Phase 2, double-blind, placebo-controlled RCT, 100 weeks
- Population
- 327 people with early symptomatic Alzheimer disease (259 low-to-medium tau)
- Primary outcome
- Change in iADRS
- Effect
- Progression ratio 0.84 (0.66 to 1.04) at 0.75 mg; 1.32 (1.10 to 1.58) at 3 mg
This phase 2 trial at 72 sites randomised 327 people with early symptomatic Alzheimer disease and low-to-medium tau on PET to once-daily ceperognastat 0.75 mg, 3 mg or placebo for 100 weeks. The drug inhibits O-GlcNAcase, aiming to slow tau aggregation.
There was no meaningful clinical benefit. Relative to placebo, progression was 16% slower with 0.75 mg (credible interval 0.66 to 1.04, crossing no effect) and 32% faster with 3 mg (1.10 to 1.58). No secondary clinical measure improved. Brain volume loss was smaller with both doses, and tau PET changed slightly with 3 mg. Serious adverse events were more common with 3 mg (26.4% vs 15.7% placebo).
The mismatch between imaging and clinical results is a caution against reading biomarker changes as benefit. For patients and families asking about new tablet treatments for Alzheimer disease, this one is not one of them.
- Ceperognastat did not slow early Alzheimer disease
- The higher dose was associated with faster decline and more serious adverse events
- Brain volume and PET changes did not translate into clinical benefit
- Advise families that oral anti-tau drugs remain experimental
Why it matters
It is another reminder that imaging biomarkers can move without patients benefiting.
The statistics, in plain English
A progression ratio of 1.32 means 32% faster decline than placebo. Credible intervals are the Bayesian equivalent of confidence intervals.
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