Alzheimer¶s Disease Today and Tomorrow

3 0 2 5 2 0 1 5 1 0 5
Source: Clinical Diagnosis and Management of A.D.

Early
Symptoms Diagnosis

Mild

Moderate

Severe

Loss of Functional Independence Behavioral Problems Nursing Home Placement Death

1 9

2

3

4 5 Years

6

7

8

Current Drugs for Alzheimer¶s Disease
Tacrine (Cognex®) Donepezil (Aricept®) Rivastigmine (Exelon ®) Galantamine (Reminyl®) Memantine (Namenda®) Warner Lambert Pfizer-Eisai Novartis Janssen Forest 1993 1997 2000 2001 2003

Proposed Classification
PrePre-symptomatic
Current Clinical practice

Mild Cognitive Impairment Dementia

Alzheimer¶s Disease:
Course, Prevention, Treatment Strategies Disease Progression
Intervention Primary Prevention
PrePresymptomatic AD

Secondary Prevention
Mild Cognitive Impairment

Treatment

Clinical State

Normal

AD

Numbers
Brain Pathologic State Strategies

???
No Disease No Symptoms

20 to 60 Mil 10 to 15 Mil 5.0 Mil
Early Brain Changes No Symptoms Prevent or Delay Emergence Of Symptoms AD Brain Changes Mild Symptoms Stimulate Memory; Slow progression Mild, Moderate, or Severe Impairment Treat cognition Treat behaviors Slow progression

Identify at-risk atPrevent AD

The Classical Drug Discovery/Development Process

Target Discovery

Hit to Lead

Lead Optimization

Preclinical Development

Clinical Development

FDA Filing/ Approval

New drug

Target ID Target Validation

Assay Development Screening Validate hits

Medicinal chemistry refinement

Scale-up, process chemistry PK, in vivo pharmacology Safety pharmacology

IND Phase I Phase II Phase III

FDA review Market application & Launch preparation FDA approval

Phase IV Postmarketing testing

Product lifetime

It¶s a long process.
Discovery to FDA approval of new drug: 12-15 years

It¶s also expensive! Current estimates: Costs >$800M-$1.2B to develop a new drug

Alzheimer Therapies in Phase III Clinical Trials
Dimebon Semagacestat (LY-450139) Solanezumab (LY-2062430) Bapineuzumab IVIg (intravenous immunoglobulin) Resveratrol Vitamin E + Memantine

Science Activities of the Alzheimer¶s Association
Grant Program Trial Match ICAD ISTAART ADNI, WW-ADNI, PIB add-on study Genetics consortia Research Roundtable Drug approval process at FDA NIA Prevalence Conference Diagnostic Criteria Alzheimer¶s Disease Centers