Evidence map›Paper›PMID 38902572›Full record

Trial reportDrugs2024

Analysis of Cerebrospinal Fluid, Plasma β-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model.

John A Hey, Jeremy Y Yu, Susan Abushakra, Jean F Schaefer, Aidan Power, Patrick Kesslak, Martin Tolar

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Drugs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04693520 (A Phase 2, Single-arm Study of the Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease Who Are Carriers of the ε4 Variant of the Apolipoprotein E Gene), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04693520 phase2completednot on this map

A Phase 2, Single-arm Study of the Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease Who Are Carriers of the ε4 Variant of the Apolipoprotein E Gene (APOE4/4 or APOE3/4)

TypeinterventionalSponsorAlzheon Inc.Ran2020 to 2025Enrolled84ConditionsEarly Alzheimer's DiseaseArmsALZ-801
3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Trial
  4. Review
  5. Beyond the Cochrane review: Re-evaluating anti-amyloid therapy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Review
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

John A HeyAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA. john.hey@alzheon.com.ORCID http://orcid.org/0000-0002-5104-6231
Jeremy Y YuAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.
Susan AbushakraAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.
Jean F SchaeferAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.
Aidan PowerAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.
Patrick KesslakAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.
Martin TolarAlzheon, Inc., 111 Speen Street, Suite 306, Framingham, MA, 01701, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionALZ-801/valiltramiprosate is an oral, small-molecule inhibitor of beta-amyloid (Aβ) aggregation and oligomer formation in late-stage development as a disease-modifying therapy for early Alzheimer's disease (AD). The present investigation provides a quantitative systems pharmacology (QSP) analysis of amyloid fluid biomarkers and cognitive results from a 2-year ALZ-801 Phase 2 trial in APOE4 carriers with early AD.

methodsThe single-arm, open-label phase 2 study evaluated effects of ALZ-801 265 mg two times daily (BID) on cerebrospinal fluid (CSF) and plasma amyloid fluid biomarkers over 104 weeks in APOE4 carriers with early AD [Mini-Mental State Examination (MMSE) ≥ 22]. Subjects with positive CSF biomarkers for amyloid (Aβ

resultsA total of 84 subjects were enrolled. Excluding one subject who withdrew at the early stage of the trial, data from 83 subjects were used for this analysis. The ALZ-801 treatment arrested the progressive decline in CSF Aβ

conclusionsIn this genetically defined and biomarker-enriched early AD population, the QSP analysis demonstrated a positive therapeutic effect of oral ALZ-801 265 mg BID by arresting the natural decline of monomeric CSF and plasma amyloid biomarkers, consistent with the target engagement to prevent their aggregation into soluble neurotoxic oligomers and subsequently into insoluble fibrils and plaques over 104 weeks. Accompanying the amyloid biomarker changes, ALZ-801 also stabilized the natural trajectory decline of the RAVLT memory test, suggesting that the clinical benefits are consistent with its mechanism of action. This sequential effect arresting the disease progression on biomarkers and cognitive decline was more pronounced in the earlier symptomatic stages of AD. The QSP analysis provides fluid biomarker and clinical evidence for ALZ-801 as a first-in-class, oral small-molecule anti-Aβ oligomer agent with disease modification potential in AD. TRIAL REGISTRY: https://clinicaltrials.gov/study/NCT04693520.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4BiomarkersCognitionHeterozygoteTaurineAdministration, OralAgedFemaleHumansMaleMiddle AgedNetwork PharmacologyPeptide Fragmentstau ProteinsAmyloid beta-PeptidesApolipoprotein E4BiomarkersPeptide Fragmentstau ProteinsTaurinetramiprosate

Identifiers

PMID38902572
PMCPMC11289344

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.