Safety and ARIA Results of the Oral Anti‐Amyloid Agent Valiltramiprosate from the Phase 3 APOLLOE4 Trial in APOE4/4 Homozygotes with Early AD
Bibliographic record
Abstract
BACKGROUND: Valiltramiprosate/ALZ-801, an oral inhibitor of amyloid oligomer formation, was evaluated in a Phase 3 trial in APOE4/4 homozygotes with Early AD, with main results presented at this meeting (Power et al, 2025). APOE4 is a risk factor for cerebral amlyloid angiopathy (CAA) and ARIA. Tramiprosate (active agent in ALZ-801) had shown no ARIA-E in prior studies, allowing the APOLLOE4 trial to include subjects with any number of microhemorrhages (MH) and several siderosis lesions at screening MRI. METHOD: This 78-week placebo-controlled trial enrolled 325 homozygotes who received placebo or 265 mg BID. Anti-coagulants were exclusionary. In addition to adverse event (AE) assessments, MRIs were performed every 26 weeks and evaluated by Clario Inc. for occurrence of ARIA with edema and/or microhemorrhage/siderosis (ARIA-E, ARIA-H). RESULT: Safety population (N =325) was 51% females, 89% Caucasian, mean age 68 years, MMSE 25.6, with MCI vs. Mild AD (39% vs 61%); 298 had screening MRI (149/arm provided ≥1 post-dose MRI). At baseline, 32% had >1 MH (placebo, 32%, active, 31%); 11% in placebo and 8% in active arm had siderosis (maximum 4 and 5 lesions, respectively); and 5% in each arm had ≥ 10 MH. New ARIA-E occurred during the study in 5 subjects in each arm (3%) and new macrohemorrhages in 2 subjects/arm. Increase in MH from low to high category (0, 1-4, 5-9, ≥10 MH) was seen in 14% placebo and 9% active arm. Radiographic ARIA were all mild except 1 severe (placebo) and 1 moderate (active); all were without symptoms. AEs with incidence >5% and >2x placebo rate were nausea (26%), weight decrease (14%), decreased appetite and vomiting (10% each); with lower incidence of headache, falls and dizziness in active arm. CONCLUSION: APOLLOE4 enrolled homozygotes with a high CAA burden who would be ineligibile for amyloid antibody treatments. Valiltramiprosate overall safety was favorable and consistent with prior studies. ARIA-E incidence was similar to placebo, and ARIA-H was lower than placebo with no symptomatic ARIA events over 78 weeks of treatment. Coupled with promising efficacy in MCI subjects, valiltramiprosate can provide a favorable benefit-risk profile for the high-risk APOE4/4 patients with unmet treatment need.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 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".