Pipeline Insight: Alzheimer's Disease - The Ultimate High-Risk, High-Reward Therapy Market

Published by: Datamonitor

Published: Aug. 14, 2009 - 226 Pages

Table of Contents

Overview

Catalyst

Summary

ABOUT DATAMONITOR HEALTHCARE

About the Central Nervous System pharmaceutical analysis team

Executive Summary

Strategic scoping and focus

Datamonitor insight into the Alzheimer's disease market

Related reports

Table of Contents

1. Pipeline Overview and Dynamics

Key findings

Pipeline overview

Interest remains strong in this high risk/high reward indication

Clinical trial attrition is very high in Alzheimer's disease

Movement towards more targeted drugs

Trends in the current pipeline

Comparative forecasts - Pfizer's Dimebon best positioned for commercial success

Datamonitor Pipeline Assessment Summary - disease modification enhances clinical attractiveness

Key companies involved in the Alzheimer's disease pipeline

Big Pharma companies partner their way into Alzheimer's pipeline

Elan Pharmaceuticals

Pfizer and Wyeth

Key R&D company strategies

Diverse drug discovery approaches

Beta-amyloid is the primary drug discovery target

Secondary indications are possible but not yet under development

2. Alzheimer's Disease: Market Potential

Key findings

Definition

Overview

World Health Organization classification and scope

1) Alzheimer's disease-specific sales

2) Other dementia-specific sales

3) Mild cognitive impairment

Syndrome description and patient segmentation

Dementia

Alzheimer's disease

Mild cognitive impairment

Mild cognitive impairment subtypes

Mild cognitive impairment subtypes and their links to Alzheimer's disease

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

Epidemiology

Seven major markets

Alzheimer's disease prevalence and patient population

Alzheimer's disease prevalence estimates methodology

Alternative US patient population estimates

Patient population projections across the seven major markets

Rest of the world

Lower current prevalence rates than in more developed markets

Projected demographic changes drive growth in Alzheimer's disease population

Diagnosis rate of cognitive disorders

Dementia (including Alzheimer's disease)

Mild cognitive impairment

Current treatment options

Brand dynamics and key past events

Drug profiles

Historical sales and off-label prescribing

Current gold standard and comparator therapies

Gold standard or comparator therapy: Aricept

Leading Alzheimer's disease therapy

Superior efficacy did not drive the success of Aricept

Current market overview

Global Alzheimer's disease market

Alzheimer's disease-specific sales across the seven major markets

Unmet need in Alzheimer's disease

Disease modifying/slowing treatments

Early treatment with disease slowing drugs should produce a better outcome

Improved symptomatic efficacy

Better diagnostic tools

Current diagnostic techniques are subjective

Better diagnostics required for early treatment and a better outcome

Better understanding of the disease etiology

Current level of attainment vs. target product profile

Different efficacy expectations for symptomatic or disease modifying treatments

Safety and tolerability

Formulation/dosing

Target population

Price

3. R&D Approach

Key findings

Clinical trial design in Alzheimer's disease

What constitutes disease modification?

Determination of disease modification

Clinical trial endpoints

Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog)

Alzheimer's Disease Cooperative Study: Activities of Daily Living (ADCS-ADL)

Mini-Mental Status Exam

Clinician's Interview-Based Impression of Change

Neuropsychiatric Inventory

Utilization in Dementia

Neuropsychological Test Battery

Severe Impairment Battery

Clinical Dementia Rating

4. Pipeline Analysis & Forecasts: Drugs targeting beta-amyloid

Key findings

Overview for drugs targeting beta-amyloid

Pipeline summary

Beta-amyloid theory

Better understand of the role of beta-amyloid is still required

Passive immunotherapy and vaccines

Secretase modulation

Aggregation inhibition

Comparative forecasts

Bapineuzumab - passive immunotherapy

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Clinical outcome

MRI measure of cerebral volume change

Ongoing clinical trials

Clinical attractiveness

Patient potential

Regular monitoring

Commercial attractiveness

Price of bapineuzumab and influencing factors

Bapineuzumab market penetration

Marketing resources and expertise unprecedented

Competition in passive immunization

Datamonitor drug assessment score card for bapineuzumab

Satisfaction of unmet needs

Forecasts to 2018

Gammagard - passive immunotherapy

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Baxter Phase II clinical trial

Other studies investigating the use of immunoglobulin in Alzheimer's disease

Ongoing Phase III clinical trial

Clinical attractiveness

Commercial attractiveness

Competing immunoglobulin is in development

Large scale production may represent a challenge

Datamonitor drug assessment score card for Gammagard

Satisfaction of unmet needs

Forecasts to 2018

Other drugs targeting beta-amyloid

LY450139 - gamma secretase

Drug overview

Clinical trial data

Ongoing clinical trials

Datamonitor's comment

PBT2 - aggregation inhibition

Drug overview

Clinical trial data

Datamonitor's comment

LY2062430 - passive immunotherapy

Drug overview

Clinical trial data

PF-04494700 - other beta-amyloid

Drug overview

Phase IIa clinical results

Ongoing clinical trial program

Posiphen - other beta-amyloid

Drug overview

Previous clinical trial failure with the negative enantiomer of phenserine

Amyloid vaccines ACC-01 and CAD106

ACC-001

CAD106

Good antibody response but no clinical efficacy signal

Octagam - passive immunization

Drug overview

ELND005 - beta-amyloid aggregation inhibitor

Drug overview

ACI91 - beta-secretase inhibition

Drug overview

EHT0202 - alpha-secretase activator

Drug overview

NIC515 - gamma-secretase inhibitor

Drug overview

ARC029 - other beta-amyloid

Drug overview

PF4360365 - passive immunization

Drug overview

Late-stage development compounds recently discontinued

Flurizan

Alzhemed

5. Pipeline Analysis & Forecasts: Drugs targeting tau hyperphosphorilation

Key findings

Overview for drugs targeting tau tangles

Pipeline summary

Rember - tau hyperphosphorylation inhibitor

Drug overview

Clinical trial data

Datamonitor's comments

Patient potential

Potential pricing

Other drugs targeting tau tangles

AL108 - tau hyperphosphorylation inhibitor

NP-12 - Glycogen synthase kinase-3 beta inhibitor

Drug overview

GSK-3 beta hypothesis of Alzheimer's disease

Basic research identifies the GSK-3 beta target

Preclinical in vivo analysis conducted with NP-12

Phase I safety trial

Ongoing Phase II clinical trial

Datamonitor's comment

6. Pipeline Analysis & Forecasts: General neuroprotective drugs

Key findings

Overview for general neuroprotective drugs

Pipeline summary

Dimebon - MPTP, NMDA, cholinesterase inhibitor

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Estimation of disease modifying effects with Staggered Start and Natural History Staggered Start approach

Preclinical animal studies suggest beta-amyloid modulation

Ongoing clinical trials

Clinical attractiveness

Clinical significance of Dimebon's various mechanisms of action yet to be established

Inconvenient dosing regime

Broad cognitive disorder patient potential

Commercial attractiveness

Potential for combination therapy with Aricept

Pfizer partnership greatly expands the drug's commercial potential

Lifecycle management planning

Cost of Dimebon

Datamonitor drug assessment score card for Dimebon

Satisfaction of unmet needs

Forecasts to 2018

Other drugs with general neuroprotective characteristics

Memryte - Gonadotrophin releasing hormone

Drug overview

Clinical trial data

HF0220 - endogenous human steroid

Drug overview

Cogane - neurotrophic factor inducer

Drug overview

T817MA - neurotrophic agent

Drug overview

7. Pipeline Analysis & Forecasts: Symptomatic Relief

Key findings

Overview for drugs targeting symptomatic relief

Pipeline summary

Acetylcholinesterase inhibitors

NMDA receptor antagonism

Neuronal nicotinic receptor agonism

5-HT6 receptor antagonist

Other targets

Comparative forecasts

Aricept SR - acetylcholinesterase inhibitor

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Clinical attractiveness

Commercial attractiveness

Switching between brands

Price for Aricept SR

Datamonitor drug assessment score card for Aricept SR

Satisfaction of unmet needs

Forecasts to 2018

Aricept patch - acetylcholinesterase inhibitor

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Clinical attractiveness

Commercial attractiveness

Price for Aricept patch

Datamonitor drug assessment score card Aricept patch

Satisfaction of unmet needs

Forecasts to 2018

Memantine extended-release -NMDA receptor antagonist

Drug overview

Drug profile

SWOT analysis

Clinical trial data

Clinical attractiveness

Commercial attractiveness

Datamonitor drug assessment score card for memantine extended-release

Satisfaction of unmet needs

Forecasts to 2018

Other drugs targeting symptomatic relief

Huperzine A - acetylcholinesterase inhibitor

Drug overview

Clinical trial data

Chinese clinical trial investigating the efficacy of Huperzine A

Small-scale trial investigating the efficacy and safety of Huperzine A

Mimopezil/Debio9902 SR - acetylcholinesterase inhibitor

Drug overview

Ongoing clinical trial program

Ispronicline/AZD3480 - neuronal nicotinic receptor agonist

Drug overview

Clinical trial data

Pozanicline/ABT-089 - neuronal nicotinic receptor agonist

Drug overview

R3487 - neuronal nicotinic receptor agonist

Drug overview

Clinical trial data

Ongoing clinical trials

EVP6124 - neuronal nicotinic receptor agonist

Drug overview

SAM-531 - 5-HT6 receptor antagonist

Drug overview

Ongoing clinical trials

SB-742457 - 5-HT6 receptor antagonist

Drug overview

Clinical trial data

Ongoing clinical trials

PRX03140 - 5-HT4 receptor agonist

Drug overview

Clinical trial data

Ongoing clinical trials

CX717 - AMPA receptor agonist

Drug overview

MK-0249

Drug overview

Ongoing clinical trial program

8. Innovative Early-Stage Approaches

Key findings

Delivery across the blood-brain barrier

Carniotomy-based drug delivery

EC Biodelivery, NSgene

Molecular Trojan horse

ArmaGen's neurotrophin and AGT-160

Tau immunotherapy

The future of treatment in Alzheimer's disease

Prophylactic treatment

Biomarkers significantly expand the patient population

Structural imaging - MRI

Functional imaging - PET and SPECT

Radiotracer fluorodeoxyglucose

Beta-amyloid radioligands using PET scans

Tau neurofibrillary tangles

Urine and serum biomarkers

Bibliography

Journals

Web-site

APPENDIX

Methodology

Datamonitor forecast methodology

Contributing experts

About Datamonitor

About Datamonitor Healthcare

About the Disease analysis team

Datamonitor consulting

Disclaimer

List of Tables

Table 1: Products in Phase II/III clinical development for Alzheimer's disease, 2009

Table 2: Sales forecasts ($m) for each pipeline drug, 2010-18

Table 3: Elan's Alzheimer's disease late-stage pipeline, 2009

Table 4: Pfizer/Wyeth Alzheimer's disease late-stage pipeline, 2009

Table 5: DIAG4 (ICD-10 derived) codes constituting >1% of total brand sales for drugs approved for Alzheimer's disease, 2008

Table 6: Dementia ICD-10 codes

Table 7: Forms of dementia

Table 8: Common clinical features in Alzheimer's disease

Table 9: Population size and prevalence rate of Alzheimer's disease and other cognitive disorders across the seven major pharmaceutical markets, 2009

Table 10: Age-group trends in Alzheimer's disease prevalence

Table 11: Current and projected patient populations (millions) for cognitive disorders, 2008-18

Table 12: Alzheimer's disease prevalence and patient population comparison across the seven major pharmaceutical markets and BRIC countries, 2009

Table 13: Projected Alzheimer's disease population across the seven major pharmaceutical markets, the 5EU and the BRIC nations, 2008-18

Table 14: Leading treatments for Alzheimer's disease, 2009

Table 15: Total brand and indication-specific sales for drugs approved for Alzheimer's disease, ($m), 2008

Table 16: Percentage of total brand sales attributed to each indication group, 2004-08

Table 17: Aricept (donepezil) - drug profile, 2009

Table 18: Efficacy of acetylcholinesterase inhibitors as measured by change in ADAS-Cog above placebo

Table 19: Head-to-head clinical trials of Aricept and other acetylcholinesterase inhibitors

Table 20: Comparison of acetylcholinesterase inhibitor treatment response outcomes, according to a meta-analysis of clinical trials

Table 21: Minimum acceptable product profile and target product profile

Table 22: Typical Phase III clinical trial design in Alzheimer's disease, 2009

Table 23: Key products in late-stage R&D pipeline targeting beta-amyloid, 2009

Table 24: Sales forecasts ($m) for beta-amyloid focused pipeline drugs across the seven major pharmaceutical markets, 2012-18

Table 25: Bapineuzumab - drug profile, 2009

Table 26: Bapineuzumab vs. the minimum acceptable product profile and target product profile

Table 27: Impacting factors on the revenues of bapineuzumab, 2009-18

Table 28: Bapineuzumab forecast methodology, US, 2012-18

Table 29: Bapineuzumab forecast methodology, 5EU, 2012-18

Table 30: Bapineuzumab forecast methodology, Japan, 2012-18

Table 31: Bapineuzumab forecast across the seven major markets ($m), 2012-18

Table 32: Gammagard - drug profile, 2009

Table 33: Gammagard vs. minimum acceptable product profile and target product profile

Table 34: Gammagard forecast methodology, US, 2012-18

Table 35: Gammagard forecast methodology, 5EU, 2012-18

Table 36: Gammagard forecast methodology, Japan, 2012-18

Table 37: Gammagard forecast across the seven major markets ($m), 2012-18

Table 38: Ongoing LY450139 clinical trials

Table 39: Key products in late-stage R&D pipeline targeting tau tangles, 2009

Table 40: Clinical trial results for high dose of AL-108 (15mg twice a day) in mild cognitive impairment subjects

Table 41: Key products in late-stage R&D pipeline with a general neuroprotective mechanism, 2009

Table 42: Dimebon - drug profile, 2009

Table 43: Mean change from baseline on the ADAS-Cog at weeks 12 and 26 in the intention-to-treat population

Table 44: Estimates from Dimebon Staggered Start and NHSS

Table 45: Ongoing Dimebon clinical trials, 2009

Table 46: Dimebon vs. the minimum acceptable product profile and target product profile

Table 47: Dimebon forecast methodology, US, 2012-18

Table 48: Dimebon forecast methodology, 5EU, 2012-18

Table 49: Dimebon forecast methodology, Japan, 2012-18

Table 50: Dimebon forecast across the seven major markets ($m), 2012-18

Table 51: Key products in late-stage R&D pipeline providing symptomatic relief, 2009

Table 52: Sales forecasts for pipeline symptomatic treatments across the seven major pharmaceutical markets, ($m), 2010-18

Table 53: Aricept SR (donepezil sustained release) - drug profile, 2009

Table 54: Aricept SR vs. the minimum acceptable product profile and target product profile

Table 55: Aricept SR forecast methodology, US, 2010-18

Table 56: Aricept SR forecast methodology, 5EU, 2011-18

Table 57: Aricept SR forecast methodology, Japan, 2012-18

Table 58: Aricept SR forecast across the seven major markets, 2010-18

Table 59: Aricept patch - drug profile, 2009

Table 60: Aricept patch vs. the minimum acceptable product profile and target product profile

Table 61: Aricept patch forecast methodology, US, 2010-18

Table 62: Aricept patch forecast methodology, 5EU, 2010-18

Table 63: Aricept patch forecast methodology, Japan, 2012-18

Table 64: Aricept patch forecast across the seven major markets, 2010-18

Table 65: Memantine extended release - drug profile, 2009

Table 66: Memantine extended-release vs. the minimum acceptable product profile and target product profile

Table 67: Memantine extended-release forecast methodology, US, 2010-18

Table 68: Memantine extended-release forecast methodology, 5EU, 2010-18

Table 69: Memantine extended-release forecast across the seven major markets, 2010-18

Table 70: Tracers for beta-amyloid plaques and other hallmarks of Alzheimer's disease

Table 71: Example of alternative tests to cerebrospinal fluid biomarkers in neurological conditions

List of Figures

Figure 1: Late-stage pipeline Alzheimer's disease drugs by class, 2009

Figure 2: Datamonitor Pipeline Assessment Summary for Alzheimer's disease, 2009

Figure 3: Companies with more than one late-stage product in development of Alzheimer's disease, 2009

Figure 4: Potential relation between symptom classification and outcomes in mild cognitive impairment patients

Figure 5: Prevalence of mild cognitive impairment (MCI) symptom and outcome subtypes

Figure 6: Patient population estimates derived from different US Alzheimer's disease estimates, 2009

Figure 7: Projected patient population for all cognitive disorders across the seven major markets, 2005-18

Figure 8: Demographic changes in the general US population, 2005-18

Figure 9: Alzheimer's disease patient population across the seven major pharmaceutical markets and BRIC nations, 2005-18

Figure 10: Percentage change in elderly population (65 years and older), 2009-18

Figure 11: Percentage of total brand sales Aricept, Namenda, Exelon and Razadyne (inc ER version sales) for Alzheimer's disease, other dementia, and mild cognitive impairment across the seven major markets, 2008

Figure 12: Alzheimer's disease-specific sales revenue generated by Aricept across the seven major pharmaceutical markets, ($m), 2009

Figure 13: Percentage of total Aricept brand sales for each indication group, 2004-08

Figure 14: Regional distribution of global Alzheimer's disease-specific sales for the four drugs approved for Alzheimer's disease, 2008

Figure 15: Alzheimer's disease-specific sales revenue across the seven major markets, ($m), 2004-08

Figure 16: Percentage of total brand sales for each indication group, 2004-08

Figure 17: Unmet need in Alzheimer's disease treatment, 2009

Figure 18: Cognitive decline of untreated Alzheimer's disease patients and patients treated with a symptomatic drug

Figure 19: Alzheimer's disease symptom progression in the presence of a disease slowing therapy

Figure 20: Alzheimer's disease symptom progression in the presence of a disease modifying treatment administered at an early stage of the disease due to better diagnostic tools

Figure 21: Alzheimer's disease symptom progression in the presence of a disease modifying treatment administered at an early stage of the disease due to better diagnostic tools

Figure 22: Clinical trial designs proposed to determine disease modification

Figure 23: Amyloidogenic pathway: formation of toxic beta-amyloid

Figure 24: Proposed passive immunization mechanism of action in Alzheimer's disease

Figure 25: SWOT analysis for bapineuzumab, 2009

Figure 26: Bapineuzumab Phase II clinical trial design and results

Figure 27: Datamonitor's competitive positioning analysis of bapineuzumab in Alzheimer's disease, 2009

Figure 28: Sales forecasts for bapineuzumab in the seven major markets ($m), 2010-18

Figure 29: SWOT analysis for Gammagard, 2009

Figure 30: Datamonitor's competitive positioning analysis of Gammagard in Alzheimer's disease, 2009

Figure 31: Sales forecasts for Gammagard (immunoglobulin) in the seven major markets ($m, 2012-18

Figure 32: LY450139 Phase II clinical trial design and results

Figure 33: SWOT analysis forDimebon, 2009

Figure 34: Datamonitor's competitive positioning analysis of Dimebon in Alzheimer's disease, 2009

Figure 35: Sales forecasts for Dimebon in the seven major markets ($m), 2012-18

Figure 36: SWOT analysis for Aricept SR, 2009

Figure 37: Datamonitor's competitive positioning analysis of Aricept SR in Alzheimer's disease, 2009

Figure 38: Sales forecasts for Aricept SR in the seven major markets, ($m), 2010-18

Figure 39: SWOT analysis for Aricept patch, 2009

Figure 40: Percentage of total sales for Exelon oral and Exelon patch in the US, 2008

Figure 41: Datamonitor's competitive positioning analysis of Aricept patch in Alzheimer's disease, 2009

Figure 42: Sales forecasts for Aricept patch in the seven major markets. 2010-18 ($m)

Figure 43: SWOT analysis for memantine extended-release, 2009

Figure 44: Efficacy of memantine extended-release in moderate-to-severe Alzheimer's disease

Figure 45: Datamonitor's competitive positioning analysis of memantine extended-release in Alzheimer's disease, 2009

Figure 46: Sales forecasts for memantine extended-release in the seven major markets. 2010-18 ($m)

Abstract

• Forecasts to 2018 for Alzheimer's disease, total dementia, and mild cognitive impairment for novel disease-modifying agents in the seven major markets
• Forecasts to 2018 of current brand reformulations targeting the symptomatic relief market.
• Provides a global Alzheimer's disease market snapshot, and analysis of patient population growth trends in the seven major markets and BRIC nations.
• Discusses the requirement for biomarker development and targeting patients earlier in the course of their disease.

• Quantify the current size of the global Alzheimer's disease market.
• Appreciate the demographic changes leading to anticipated growth in the Alzheimer's disease market.
• uantify the market to 2018 in the US, Japan, and five key European markets while identifying the major drivers, resistors, and risks.

About MarketResearch.com
MarketResearch.com is an online aggregator selling over 250,000 market research reports, company profiles and country profiles from over 650 research firms. Our reports will provide you with the critical business and competitive intelligence you need for strategic planning and marketing research. Coverage includes the US, UK, Europe, Asia and global markets.