Pipeline Insight: Mild Cognitive Impairment - Unlocking the potential of prodromal Alzheimer's disease and beyond

Published by: Datamonitor

Published: Apr. 1, 2009 - 196 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Central Nervous System pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the mild cognitive impairment market

Key metrics

Datamonitor Pipeline Assessment Summary

Contributing experts

Related reports

Upcoming reports

CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS

Pipeline overview

Lack of pipeline drugs targeting mild cognitive impairment

Mild cognitive impairment pipeline dominated by potentially disease-slowing therapies

Key companies involved in the mild cognitive impairment pipeline

Allon Therapeutics

The only company targeting amnestic mild cognitive impairment as a primary indication

AL-108 showed mixed Phase II results in amnestic MCI patients

The heterogeneity of the amnestic mild cognitive impairment population may induce misleading Phase II results

Trials in mild cognitive impairment patients should not be conducted before the development of diagnostic tools specific to each disease subtype

Pfizer/Medivation/Wyeth

Presence in the current market with Aricept

License agreements and mergers develop potential MCI portfolio

Key R&D company strategies

Mild cognitive impairment - a future indication expansion opportunity

Working on the development of better diagnostic tools

Wyeth has already partnered with diagnostic company Adlyfe to develop better tools

TauRx Therapeutics is developing its own biomarkers

CHAPTER 3 PATIENT POTENTIAL

Definition of mild cognitive impairment

Mild cognitive impairment - a borderline condition between normal aging and dementia

Evolution of mild cognitive impairment definition

Mild cognitive impairment diagnostic criteria

Clinical segmentation of mild cognitive impairment

Working areas and their significance for pharmaceutical companies

The broad definition of mild cognitive impairment is problematic for the development and approval of new drugs

Mild cognitive impairment - an early status of several dementia

Ongoing discussion on the inclusion of mild cognitive impairment in DSM-V

Uncertainty for the inclusion of psychiatric and somatic cognitive impairments in mild cognitive impairment

Cognitive disorders - mild cognitive impairment and beyond

Other definitions of cognitive impairments - both broader and narrower than mild cognitive impairment

Cognitive impairments in international diseases classifications

Epidemiology of mild cognitive impairment

Prevalence of mild cognitive impairment

Mild cognitive impairment affects up to 20% of the seven major markets' population aged 65 years and over

Mild cognitive impairment prevalence increases with age

Prevalence and progression of mild cognitive impairment subtypes

Mild cognitive impairment patients are at increased risk for dementia

Alzheimer's disease is the most frequent outcome of mild cognitive impairment

Link between amnestic mild cognitive impairment and early dementias

Imprecise relationship between symptoms and outcomes

Relationship between amnestic-mild cognitive impairment and prodromal Alzheimer's

Different types of dementia

Treatable population

Number of treated MCI patients estimated at around 548,300 in 2007

Presentation and diagnostic combined rate lower than 10% in MCI

Mild cognitive impairment treatable population in 2007

Segmentation of the mild cognitive impairment population in 2007

Etiology of mild cognitive impairment

Etiology of mild cognitive impairment can be linked to underlying neurodegenerative disorder

Causes of mild cognitive impairment - Alzheimer's disease etiology

Causes of mild cognitive impairment - frontotemporal dementia etiology

Diagnosis of mild cognitive impairment

Lack of consensus in diagnostic tools

Heterogeneity of mild cognitive impairment measures and rating scales

Variability on normal reference standards across studies

Accurate diagnosis may demand a combination of exams

Diagnostic tools

Neuroimaging tests - a beneficial tool for mild cognitive impairment future diagnosis

Proposed criteria for effective biomarkers in mild cognitive impairment

Example of other biomarkers potentially suitable to MCI

Urine and serum biomarkers

Neurological tests and questionnaires

Unmet needs in mild cognitive impairment

Unmet need overview

Consensus on the definition and categorization of mild cognitive impairment

Improving the definition of each subtype of the mild cognitive impairment population in correlation with a specific outcome

Development of diagnostic tools

Need to develop diagnostic tools able to identify specific subtypes of patients

Consensus on diagnosis criteria

Specific and sensitive biomarkers could help to diagnose mild cognitive impairment patients likely to progress to Alzheimer's disease or other dementia

Need for more sensitive neurological tests

Development of therapeutic solution

Delay of progression to dementia with the approval of disease-slowing drugs

Approval of effective symptomatic drugs will slightly improve MCI patients' quality of life

CHAPTER 4 MARKET OVERVIEW AND POTENTIAL

Current market size

Market value methodology

Mild cognitive impairment-specific sales estimate methodology

ATC class choice

Medical data for indication-specific sales

Age range choice

Mild cognitive impairment-specific sales calculations

MCI market value estimates

MCI-specific market value estimated at $440m in 2007

Mild cognitive impairment sales revenue led by anti-Alzheimer's products

Disparities in mild cognitive impairment market across regions

Forecast methodology

Overview of Datamonitor's forecast methodology

Evolution in patient numbers over the forecast period

Mild cognitive impairment presentation and diagnosis combined rate forecast to increase from around 8% in 2007 to 20.1% in 2018

Market forecast overview

Total market forecasts

MCI-specific sales revenue expected to increase by seven-fold to 2018

Key late-stage pipeline drug forecasts

CHAPTER 5 R&D APPROACH

Classification of pipeline products

Lack of pipeline drugs targeting MCI as a primary indication

Patient potential

Patient potential of pipeline drugs depends on their mechanism of action

Symptomatic treatments

Symptomatic drugs possess a large patient potential

Disease-modifying treatments

Disease-slowing treatments will satisfy the most important unmet need of mild cognitive impairment

Clinical trial design in mild cognitive impairment

CHAPTER 6 POTENTIAL DISEASE SLOWING THERAPIES

Overview for potentially disease-slowing therapies

Definition of current comparator therapy - Aricept

Aricept - a symptomatic drug prescribed off-label for the treatment of mild cognitive impairment

Aricept's strengths and weaknesses

Historical sales for Aricept and other anti-Alzheimer's diseases drugs in mild cognitive impairment

Factors required to compete with Aricept

Bapineuzumab

Drug overview

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Japan - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price of bapineuzumab and influencing factors

Competitive environment

Bapineuzumab market penetration

Patient potential

Potential limited to ApoE4 non-carriers with prodromal Alzheimer's disease'

Intravenous administration and MRI monitoring

Satisfaction of unmet needs

Clinical trial data

Positive post-hoc analysis results in ApoE-negative patients with mild-to-moderate Alzheimer's disease patients

Phase II clinical trial data

Ongoing clinical trials

LY450139 - semagacestat

Drug overview

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Japan - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price for LY450139 and influencing factors

LY450139 market penetration

Competitive environment

Patient potential

LY450139's potential limited to MCI patients with prodromal Alzheimer's disease symptoms

Satisfaction of unmet needs

Clinical trial data

Ongoing and completed clinical trials

Phase II results: reduction of beta-amyloid fragment (1-40) concentration in plasma but no change in cognition

Gammagard

Drug overview

Gammagard's large production may represent a challenge

Forecasts to 2018

US - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price for Gammagard and influencing factors

Gammagard market penetration

Patient potential

Gammagard's potential possibly limited to prodromal Alzheimer's disease MCI patients

Satisfaction of unmet needs

Clinical trial data

Phase II clinical trial

Ongoing Phase III clinical trial

Rember

Drug overview

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price for Rember and influencing factors

Rember market penetration

Patient potential

Rember potential possibly limited to MCI patients with prodromal Alzheimer's disease symptoms

Satisfaction of unmet needs

Clinical trial data

A Phase IIb trial of a tau aggregation inhibitor therapy

PBT2

Drug overview

Historical research program

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price for PBT2 and influencing factors

PBT2 market penetration

Patient potential

PBT2's potential limited to prodromal Alzheimer's disease MCI patients

Satisfaction of unmet needs

Clinical trial data

Higher dose of PBT2 proved to be safe and effective in early Alzheimer's disease patients

PBT2 - preclinical results

AL-108

Drug overview

AL-108 - potential disease-slowing treatment for cognitive disorders

AL-208 - the injectable formulation of NAP

Partnership needed for further development in Alzheimer's disease

Projects for 2009

Clinical trial data

AL-108 demonstrated mixed results in amnestic MCI patients

LY2062430

Drug overview

Clinical trial data

Phase II clinical trial

PF-04494700 (TTP488)

Drug overview

Clinical trial data

Phase IIa clinical results

Ongoing clinical trial program

Rosiglitazone XR

Drug overview

Amyloid vaccines

ACC-001

Drug overview

Ongoing clinical trial

CAD106

Drug overview

Clinical trial

CHAPTER 7 SYMPTOMATIC TREATMENTS

Overview for symptomatic drugs

Definition of current comparator therapy - Aricept

Dimebon

Drug overview

A promising therapy co-developed by Medivation and Pfizer

Dimebon's mechanism of action

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Japan - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Modes of action may be confusing for prescribers

Price for Dimebon and influencing factors

Dimebon market penetration: potentially beneficial for the entire MCI population

Pfizer - a highly valuable partner in Alzheimer's disease and associated markets

Patient potential

Satisfaction of unmet needs

Clinical trial data

Impressive Phase II results in patient with mild-to-moderate Alzheimer's disease

Ongoing clinical trials

Aricept (donepezil) SR

Drug overview

Forecasts to 2018

US - forecast methodology

5EU - forecast methodology

Datamonitor drug assessment summary

Marketing factors

Price for Aricept (donepezil) SR

Aricept SR market penetration expected to decline over the forecast period

Patient potential

Satisfaction of unmet needs

SB-742457

Drug overview

Datamonitor comments

BIBLIOGRAPHY

Journals

Websites

Annual reports

Datamonitor reports

APPENDIX

Methodology

Datamonitor forecast methodology

Patent's expiry dates of key branded treatments

Current market estimate

Treatments for MCI

Definition of a standard unit (only use if ForeSight model used to forecast)

Epidemiology forecasts

Pipeline product forecasts

Contributing experts

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare's therapy area capabilities

About the Disease analysis team

Disclaimer

List of Tables

Table 1: Key parameters of mild cognitive impairment (MCI) across the seven major markets, 2007-2017

Table 2: Key pipeline product sales in mild cognitive impairment (MCI) across the seven major markets to 2018

Table 3: Key potential disease-slowing treatments in development for Alzheimer's disease and potentially appropriate for mild cognitive impairment, 2009

Table 4: Key symptomatic treatments in development for Alzheimer's disease and potentially appropriate for mild cognitive impairment, 2009

Table 5: Number of key late-stage pipeline drugs potentially suitable for mild cognitive impairment per class and phase of development, 2009

Table 6: Allon Therapeutics's drug pipeline, 2009

Table 7: Prevalence of mild cognitive impairment (MCI) in the seven major markets, 2007

Table 8: Epidemiological studies on mild cognitive impairment, 2001-08

Table 9: Description of different types of dementias mild cognitive impairment patients can go on to develop

Table 10: Mild cognitive impairment-specific sales value ($) and volume (IMS standard units, SU) and number of patients treated across the seven major markets, 2007

Table 11: Examples of cerebrospinal fluid tracers for beta-amyloid plaques and acetylcholinesterase

Table 12: Example of alternative tests to cerebrospinal fluid biomarkers in neurological conditions

Figure 9: Unmet needs in mild cognitive impairment (MCI), 2009

Table 13: ICD-10 codes excluded from mild cognitive impairment (MCI) sales estimate

Table 14: Evolution of MCI patients flow across the seven major markets, 2007-2018

Table 15: Sales forecasts for the key late-stage pipeline drugs across the seven major markets ($m), 2011-18

Table 16: Key potential disease-slowing treatments in development for Alzheimer's disease and potentially appropriate for mild cognitive impairment (MCI), 2009

Table 17: Pfizer/Eisai's Aricept: key facts, 2009

Table 18: Bapineuzumab - forecast methodology in mild cognitive impairment in the US, 2012-18

Table 19: Bapineuzumab - forecast methodology in mild cognitive impairment in the 5EU, 2012-18

Table 20: Bapineuzumab - forecast assumptions in mild cognitive impairment in Japan, 2013-18

Table 21: LY450139 - forecast methodology in mild cognitive impairment in the US, 2013-18

Table 22: LY450139 - forecast methodology in mild cognitive impairment in the 5EU, 2013-18

Table 23: LY450139 - forecast methodology in mild cognitive impairment in Japan, 2014-18

Table 24: Clinical trial summary for LY450139 in Alzheimer's disease, 2009

Table 25: Gammagard - forecast methodology in mild cognitive impairment in the US, 2013-18

Table 26: Rember - forecast methodology in mild cognitive impairment in the US, 2014-18

Table 27: Rember - forecast methodology in mild cognitive impairment in the 5EU, 2014-18

Table 28: PBT2 - forecast methodology in mild cognitive impairment in the US, 2014-18

Table 29: PBT2 - forecast methodology in mild cognitive impairment in the 5EU, 2014-18

Table 30: Clinical trial results for high dose of AL-108 (15mg twice a day) in mild cognitive impairment (MCI) subjects

Table 31: Key symptomatic treatments in development for Alzheimer's disease and potentially appropriate for mild cognitive impairment (MCI), 2009

Table 32: Dimebon - forecast methodology in mild cognitive impairment in the US, 2012-18

Table 33: Dimebon - forecast methodology in mild cognitive impairment in the 5EU, 2012-18

Table 34: Dimebon - forecast methodology in mild cognitive impairment in Japan, 2015-18

Table 35: Clinical trial summary for Dimebon in Alzheimer's disease, 2009

Table 36: Aricept (donepezil) SR - forecast methodology in mild cognitive impairment in the US, 2011-18

Table 37: Aricept (donepezil) SR - forecast methodology in mild cognitive impairment in the 5EU, 2011-18

Table 38: Patent's expiry dates of key branded anti-Alzheimer's disease drugs across the US, the 5EU and Japan

Table 39: Datamonitor drug assessment parameters

List of Figures

Figure 1: Datamonitor's drug assessment summary of key late-stage therapies in development for Alzheimer's disease and potentially effective in mild cognitive impairment, 2007-2018.

Figure 2: Number of symptomatic and potential disease-slowing late-stage pipeline drugs potentially appropriate for mild cognitive impairment, 2009

Figure 3: Diagnosis algorithm and mild cognitive impairment (MCI) segmentation according to clinical characterization of the symptoms

Figure 4: Mild cognitive impairment prevalence by age in Unverzagt et al.'s study, 2001

Figure 5: Prevalence of each subtype within the mild cognitive impairment (MCI) population

Figure 6: Potential relation between symptom classification and outcomes in mild cognitive impairment patients

Figure 7: Prevalent, diagnosed and treated population with mild cognitive impairment aged 65 and over across the seven major markets, 2007

Figure 8: Segmentation of the mild cognitive impairment population and the treatable population across the seven major markets

Figure 10: Datamonitor's mild cognitive impairment (MCI) sales methodology, 2009

Figure 11: US IMS diagnostic value sales ($m) for ATC classes N6D and N7D limited to non-dementia indications per age group, 2007

Figure 12: US IMS diagnostic value sales ($) for ATC classes N6D and N7D limited to non-dementia indications per 1,000 persons, 2007

Figure 13: Mild cognitive impairment (MCI)-specific sales value ($m) by class across the seven major markets, 2005-08

Figure 14: Mild cognitive impairment (MCI)-specific sales volume (IMS standard units) by class across the seven major markets, 2005-08

Figure 15: Mild cognitive impairment (MCI)-specific sales revenue ($m) in the US, 5EU and Japan, 2007

Figure 16: Datamonitor's methodology for estimating the treatable MCI population across the seven major markets.

Figure 17: Evolution of the mild cognitive impairment presentation and diagnosis combined rate across the seven major markets, 2005-2018

Figure 18: Number of mild cognitive impairment (MCI) patients treated by drug type across the seven major markets ($m), 2005-2018

Figure 19: Mild cognitive impairment (MCI)-specific sales revenue distribution by drug type across the seven major markets ($m), 2005-2018

Figure 20: Sales forecasts for key mild cognitive impairment-specific late-stage pipeline drugs across the major markets, 2010-2018

Figure 21: Datamonitor's drug assessment summary of key late-stage therapies in development for Alzheimer's disease and potentially effective in mild cognitive impairment, 2007-2018

Figure 22: Mild cognitive impairment patient potential according to the type of treatment

Figure 23: Aricept (donepezil) - strengths and weaknesses, 2009

Figure 24: Historical sales for the current anti-Alzheimer's disease products in the mild cognitive impairment market across the seven major markets, 2005-08

Figure 25: Off-label sales forecast for bapineuzumab in mild cognitive impairment (MCI) to 2018 across the seven major markets

Figure 26: Datamonitor's competitive positioning analysis of bapineuzumab in mild cognitive impairment across the seven major markets, 2007-2018

Figure 27: Off-label sales forecast for LY450139 in mild cognitive impairment to 2018 across the seven major markets

Figure 28: Datamonitor's competitive positioning analysis of LY450139 in mild cognitive impairment (MCI) across the seven major markets, 2007-2018

Figure 29: Off-label sales forecast for Gammagard in mild cognitive impairment (MCI) to 2018 in the US

Figure 30: Datamonitor's competitive positioning analysis of Gammagard in mild cognitive impairment (MCI) across the seven major markets, 2007-2018

Figure 31: Off-label sales forecast for Rember in mild cognitive impairment (MCI) to 2018 in the US and 5EU

Figure 32: Datamonitor's competitive positioning analysis of Rember in mild cognitive impairment (MCI) across the seven major markets, 2007-2018

Figure 33: Off-label sales forecast for PBT2 in mild cognitive impairment (MCI) to 2018 in the US and 5EU

Figure 34: Datamonitor's competitive positioning analysis of PBT2 in mild cognitive impairment (MCI) across the seven major markets, 2007-2018

Figure 35: Off-label sales forecast for Dimebon in mild cognitive impairment to across the seven major markets, 2012-2018

Figure 36: Datamonitor's competitive positioning analysis of Dimebon in mild cognitive impairment across the seven major markets, 2007-2018

Figure 37: Off-label sales forecast for Aricept (donepezil) SR in mild cognitive impairment (MCI) to 2018 in the US and 5EU

Figure 38: Datamonitor's competitive positioning analysis of Aricept (donepezil) SR in mild cognitive impairment (MCI) across the seven major markets, 2007-2018

Figure 39: Datamonitor's drug assessment summary of key late-stage therapies in development for Alzheimer's disease and potentially effective in mild cognitive impairment, 2007-2018

Abstract

• Definition and prevalence of MCI and its major sub-types.
• Review of the key unmet needs in the treatment of the MCI subtypes as identified by key opinion leaders.
• MCI-specific drug sales value and number of treated patients forecasts to 2018 in the US, Japan, and five major European markets.
• Pipeline analysis with detailed profiles for key late-stage drugs potentially appropriate for MCI patients.

• Better understand the concept of MCI and its limits in the identification of the syndromes sub-types and the approval of treatments.
• Quantify the MCI-specific market to 2018 in the US, Japan, and five major European markets and identify the drivers and resistors in this market.
• Understand unmet needs and opportunities in the definition, diagnosis and management of MCI based on key opinion leader comments.

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