Encouraging interim results at 9 months from an open‐label study of simufilam in patients with Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Simufilam is a novel drug candidate for Alzheimer’s disease (AD). This small molecule reverses an altered conformation of filamin A in the AD brain, reducing tau hyperphosphorylation and neuroinflammation initiated by Aβ42. In a prior randomized, controlled trial in 64 patients with mild‐to‐moderate AD, simufilam significantly improved eleven CSF biomarkers of AD pathology, neurodegeneration, neuroinflammation and blood‐brain barrier integrity over 28 days, with no safety issues. A one‐year, open‐label, multi‐center study is now evaluating simufilam’s long‐term safety and tolerability and following cognition and neuropsychiatric symptoms of dementia. The study has pre‐planned interim analyses at 6 and 9 months. Method Approximately 150 patients with mild‐to‐moderate AD, MMSE 16 to 26, will be enrolled across 16 sites in the US and Canada. Study participants receive 100 mg twice‐daily oral simufilam for one year. In addition to safety, patients are assessed on the 11‐item Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog11) and the 10‐item Neuropsychiatric Inventory (NPI10). Result Interim results summarize data from the first 50 patients to complete at least 9 months of treatment. Simufilam was safe and well‐tolerated, consistent with prior safety results. Six months of treatment improved patients’ cognition scores by ‐1.6 points on ADAS‐Cog11, a 10% mean improvement from baseline (negative score indicates improvement). At 9 months, ADAS‐Cog11 scores improved by ‐3.0 points, a 19% mean improvement from baseline. At 9 months, 69% of patients showed improved or stable ADAS‐Cog11 scores from baseline. Mean baseline ADAS‐Cog11 score for these 50 patients was 16. Mean baseline MMSE was 22. Six months of treatment also improved NPI scores by ‐1.3 points, a 29% mean improvement from baseline (negative score indicates improvement). At 9 months, NPI scores improved by ‐0.7 points, a 16% mean improvement from baseline. At 9 months, 76% of patients showed improved or stable NPI scores from baseline. Mean baseline NPI10 score was 4.5. Conclusion Interim analyses at 6 and 9 months indicate open‐label treatment with simufilam 100 mg improved scores of cognition and neuropsychiatric symptoms in patients with Alzheimer’s disease, with no safety issues. This work was funded by NIA grant AG065152.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".