Early Alzheimer’s Disease: Developing Drugs for Treatment | Guideline Explorer

Description

The Food and Drug Administration (FDA or Agency) is announcing the availability of a revised draft guidance for industry entitled “Early Alzheimer’s Disease: Developing Drugs for Treatment.” This draft guidance is intended to assist sponsors in the clinical development of drugs for the treatment of the stages of sporadic Alzheimer’s disease (AD) that occur before the onset of overt dementia. This draft guidance revises the previous draft guidance for industry of the same name issued on February 16, 2018.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1

monoclonal antibodies

directed against aggregated forms of amyloid beta

Stakeholders

1

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

4

Marketing approval

may provide adequate support for a marketing approval

traditional approval

Supported by direct measures of clinical benefit or validated surrogate endpoints

accelerated approval

Pathway based on surrogate endpoints reasonably likely to predict clinical benefit; support either traditional or accelerated approval

Clinical Development

The process of developing drug and biological products for CIPN.

Attributes

4

Primary efficacy outcome measure

acceptable as a single primary efficacy outcome measure in early AD patients

Stage 3

last stage of early AD

Stage 2

stage of early AD before overt dementia

Stage 1

earliest stage of sporadic Alzheimer's disease

Technical Details

Substances

2

amyloid beta

Brain burden assessed as a surrogate endpoint

Biomarkers

Used to increase development efficiency

Testing Methods

5

Neuropsychological tests

persuasive effect on cognition as measured by sensitive neuropsychological tests

Integrated scale

An integrated scale that adequately and meaningfully assesses independent effects on both daily function and cognition

positron emission tomography

Used to assess brain amyloid beta burden

neuropsychological measures

Sensitive tests used to detect subtle clinical abnormalities

Time-to-Event Analysis

outcome measure for clinical trials; Acceptable primary efficacy measure in clinical trials for early AD; a time-to-event analysis approach could also be considered

Clinical Concepts

10

Pathophysiological changes of AD

supported by similarly persuasive effects on the characteristic pathophysiological changes of AD

Functional impairment

detectable cognitive and functional impairment at this stage of disease

Cognitive impairment

detectable cognitive and functional impairment at this stage of disease

Overt dementia

Progressive stages 4, 5, and 6 of Alzheimer's disease

Stage 3 AD

Patients with mild cognitive impairment and detectable functional impairment; Patients with Stage 3 AD approaching the onset of overt dementia have relatively mild but noticeable impairments

Stage 2 AD

Patients with subtle cognitive deficits but no functional impairment

Stage 1 AD

Asymptomatic patients with pathophysiological changes but no clinical impact

Early Alzheimer’s Disease

Target population for drug development

Autosomal dominant forms of AD

specific forms of AD not primarily discussed in this guidance

Dementia

overt clinical symptoms associated with later stages of AD

Standards & References

Specifications

2

Surrogate Endpoints

outcome measures discussed in section IV.C

Clinical Endpoints

selection of endpoints for clinical trials in this population

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics