J 2024

Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review

HLÁVKA, Jakub; Andrew T. KINOSHITA; Divya JEYASINGH; Cheng HUANG; Leila MIRSAFIAN et. al.

Basic information

Original name

Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review

Authors

HLÁVKA, Jakub; Andrew T. KINOSHITA; Divya JEYASINGH; Cheng HUANG; Leila MIRSAFIAN and Mireille JACOBSON

Edition

CLINICAL INTERVENTIONS, UNITED STATES, WILEY, 2024, 2352-8737

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

Organization

Ekonomicko-správní fakulta – Repository – Repository

UT WoS

001385328600001

EID Scopus

2-s2.0-85213717106

Keywords in English

Alzheimer's disease; clinical trials; disease-modifying therapy; pharmaceutical pipeline; pharmacoeconomics

Links

LX22NPO5107, research and development project.
Changed: 8/2/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

INTRODUCTION: Without disease-modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near-total failure rate in clinical trials suggests that more disease-modifying therapies are on the horizon. In this review, we assess the late-stage pipeline of disease-modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms-groups of candidates that share an underlying biological mechanism of action and general disease target. METHODS: We extracted data from the National Library of Medicine clinical trials database regarding Phase 2 and 3 trials of disease-modifying AD therapies. We categorized trials into eight unique treatment paradigms, which we defined by combinations of therapy (biologic, small molecule, cell and gene therapy, other) and target (amyloid, tau, other). We analyzed primary endpoints, eligibility criteria including clinical ratings of cognition, trial phase and length, and funding sources. RESULTS: We identified 123 unique disease-modifying intervention candidates in 175 late-stage clinical trials. Biologic and small molecule drugs comprised 30% and 54% of trials, respectively. Eligibility criteria favored patients between the ages of 60 and 80 years with mild cognitive impairment. Including multi-phase trials, 81% of studies were engaged in Phase 2 and 27% in Phase 3. Notably, within the Biologic-Amyloid paradigm, 64% of trials were engaged in Phase 3. DISCUSSION: Current studies of disease-modifying therapies for AD comprise a diverse set of approaches to treating the disease. However, effort is largely concentrated in a few treatment paradigms and a narrow patient population, causing varying rates of progress among treatment paradigms in the late-stage clinical trial pipeline. Strategies may be warranted to accelerate successes in the most promising therapeutical paradigms and nurture growth within nascent areas lacking resources but not potential.

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