Pipeline and Commercial Insight: Alzheimer's Disease - Beta treatments on the horizon

Published by: Datamonitor

Published: Nov. 7, 2005 - 272 Pages

Table of Contents

About the CNS pharmaceutical analysis team

Objective of the analysis

Datamonitor insight into the AD market

Key opinion leaders

Key metrics

Definition of Alzheimer's disease

Segmentation of Alzheimer's disease

Mild AD affects memory, language and reasoning

Moderate AD demonstrates more pronounced symptoms

Severe AD leaves patients completely dependent

Mild cognitive impairment (MCI) may be a precursor to AD

Comorbidities or symptoms?

Treatments for comorbidities

Treating depression improves quality of life and behavior

Treatment of agitation, aggression and psychotic symptoms is limited by side effects

Anxiety is treated using antidepressants and benzodiazepines

Treatment of sleep disturbances is a difficult balance of sedation

Broad symptomatology provides commercial opportunity

Diagnosis of Alzheimer's disease is generally by exclusion

Diagnostic guidelines for AD are provided by multiple sources

Severity of AD is often assessed using symptomatic subscales

An holistic view of AD progression is lacking

Diagnosis and treatment rates restrict commercial potential

Epidemiology of Alzheimer's disease

Market definition for this report

The current AD market

The major AD market players and franchises

Acetylcholinesterase Inhibitors (AChEIs) dominate the market

Pfizer/Eisai's Aricept (donepezil)

J&J's Razadyne (galantamine) franchise

Novartis's Exelon (rivastigmine)

NMDA receptor antagonists

Forest's Namenda (memantine)

Unmet needs in Alzheimer's disease

Disease modification

Improved efficacy

Fewer side effects

Reducing numbers of treatment unresponsive patients

Patient compliance

Global opportunities and threats

Opportunities

Demographics will continue to expand the market size

Increased use of combination therapy as the disease progresses

Clinical unmet needs ensure pipeline drugs will drive future growth

Improvements in diagnosis will increase treatment rates

New EU legislation will increase data exclusivity period, providing increased return on investment for new products

Efficacy in other indications could expand the market

Threats

Introduction of generic competitors will increase focus on cost

The economic cost of geriatric healthcare puts drugs without clear benefits at risk

Parallel imports; EU expansion is likely to drive down price

US

Market overview

Opportunities

High public awareness driven by advocacy & DTC campaigns

Direct access to specialist physicians helps patients receive optimal treatment quicker

Threats

Generic entrants increase competition and impact price

Although providing drug benefit for the elderly, the future implications of the Medicare Modernization Act (MMA) are uncertain

FDA self-regulation will lead to stricter safety evaluations

Japan

Market overview

Opportunities

Under-developed market with room for expansion

Improvements in diagnosis and increased awareness would increase drug sales

Pricing process slows generic incursion

Separation of manufacturing and marketing entities opens market to overseas companies

Faster product approval accelerates the time to market

Threats

Biennial price cuts restrict profit

Healthcare reforms focus on severe reductions in pharmaceutical expenditure

Genericization is slowly taking off

France

Market overview

Opportunities

Approval in other AD subgroups would improve the target patient pool

Innovative drug development encouraged by price premium and high-level reimbursement

Threats

Healthcare reforms limit patient access to specialists

Price reductions restrict return on investment

Re-evaluation of cost-effectiveness and safety data threatens reimbursement status

Drives to promote generic substitution

Germany

Market overview

Opportunities

Promotion and education could realize the EU's greatest patient potential

Loophole in 2004 reform exploited for price increases

ePharmacy and mail-order legalization increases access to drugs and information

Threats

Focus on prescriber overspend in addition to patient co-payments support lower-priced therapies

Italy

Market overview

Opportunities

Low treatment rates suggest scope for expansion

Innovative drug development rewarded with premium price and 100% reimbursement

UVAs increasing AD treatment efforts

Threats

Legislation enforces cost-containment in a market already characterized by low pricing

Pricing can disqualify products from reimbursement

Spain

Market overview

Opportunities

Drive to improve Alzheimer's care

Regional differences provide localized opportunities

Drug innovation encouraged by enhanced financing

Threats

Regulatory and financial barriers to reimbursement

A complex pricing system compounded by regular changes and regional variation is a barrier to usual pricing strategies

Generic penetration still low but expected to increase

UK

Market overview

Opportunities

Severe AD may offer an undertreated population

Threats

NICE guidance threatens the reimbursement status of AD drugs

Health Select Committee report clamps down on pharmaceutical promotion

Pharmaceutical Price Regulation Scheme (PPRS) curbs price increases

Cost-containment measures encourage continued high use of generics

The UK is the top importer for parallel trade

Classification of pipeline products

ACh modulators are the foundation of current treatment

NMDA receptor antagonists lead the way in moderate to severe AD

Neuroprotective and neurotrophic drugs are developing from a variety of approaches

Beta-amyloid modulators reduce plaque deposition

Other compounds in development

Statins - the potential in AD is still unclear

Anti-inflammatory drugs - future hampered by safety concerns

Antioxidants may reduce cell death

Insulin's role in AD is being defined

Clinical trial characteristics in Alzheimer's disease

Gold standard

Patient population should be assessed for severity and potential responders

Trial duration must reflect chronic nature of AD

Trial endpoints should include more than cognitive function

Measurement scales in Alzheimer's disease

Alzheimer's disease assessment scale (ADAS)

Mini-Mental Status Exam

Clinician's Interview-Based Impression of Change

Severe Impairment Battery

Alzheimer's Disease Cooperative Study: Activities of Daily Living

Neuropsychiatic Inventory

Clinical Dementia Rating

Pipeline overview

Phase III overview

Phase II overview

Phase I overview

Key companies involved in the AD pipeline

Eli Lilly

Sanofi-Aventis

Key companies specializing in Alzheimer's disease

Axonyx

Mindset

Strategies for success

High risk, high profit versus low risk, low return

Diagnosis of Alzheimer's disease

Overview for beta-amyloid modulators

Pipeline summary

Definition of current comparator therapy

Alzhemed

Drug overview

Clinical trial data

Phase I

Phase II

Phase III

Patient potential

Marketing factors

Satisfaction of unmet need

Efficacy

Disease modification

Safety

Treatment response

Forecasts to 2014

Datamonitor comments

Flurizan ((R) - flurbiprofen)

Clinical trial data

Phase I

Phase II

Phase III

Patient population

Marketing factors

Satisfaction of unmet needs

Efficacy

Disease modification

Safety

Treatment response

Forecasts to 2014

Other drugs

AAB-001

Cereact/ONO-2506

LY-450139

Gero-46 (clioquinol)

Late-stage development compounds recently discontinued

PBT-1 (clioquinol)

PPI-1019/Apan

Comparison of key compounds in the beta-amyloid modulator class

Disease modification

Better efficacy than marketed drugs

Side-effect profile

Treatment unresponsive patients

Marketing strength

Commercial comparison

Comparative forecasts

Overview for acetylcholine modulators

Pipeline summary

Definition of current comparator therapy

Phenserine

Clinical trial data

Phase I

Phase II

Phase IIb

Phase III

Patient profile

Marketing factors

Satisfaction of unmet needs

Efficacy

Treatment response

Forecast to 2014

Other drugs

ZT-1

CI-1017

T-588

TV-3326

Dimebon

Late-stage development compounds recently discontinued

NS-2330

MKC-231

SIB-1553A

Overview for NMDA modulators

Pipeline summary

Definition of current comparator therapy

Neramexane

Clinical trial data

Phase III

Phase II/ III

Patient profile

Marketing factors

Satisfaction of unmet needs

Efficacy

Safety

Treatment response

Forecasts to 2014

Other drugs

Overview for neuroprotectant drugs

Pipeline summary

Definition of current comparator therapy

Xaliproden (Xaprila)

Profile

Preclinical data

Clinical trial data

Datamonitor comments

Phase III

Patient profile

Marketing factors

Efficacy

Disease modification

Safety

Treatment response

Forecasts to 2014

EGb-761 (Tanakan)

Profile

Clinical trial data

Phase III - The GEM Study

Phase III - The Guidance Study

Other drugs

PYM50028 (Cogane)

Clinical trial data

Marketing factors

SR-57667

Ampalex/CX516

CX717

Epadel/MND-21

SRA-333 (lecozotan)

LY-451395

SL65.0155

Overview for other drugs

Pipeline summary

The role of statins in AD is not yet clear

Zocor

Lipitor

Colostrinin

Clinical trial data

AC-3933/AVE-3933

Avandia (rosiglitazone)

Evista (raloxifene)

TVP-1012 (rasagiline)

SGS-742

C-1073/Corlux

C-9136

Memryte (leuprolide implant)

Immunotherapy and vaccines

AN-1792 showed promise but fell on safety issues

Evidence of Aâ clearance, but effects on cognition not clear

New immunotherapeutic approaches reignite hope for an 'Alzheimer's vaccine'

AAB-001

ACC-001

CAD-106

AutoVac for Alzheimer's PX-106

PeviPro

Mindset's â-amyloid antibodies

M266

Considerations for immunotherapeutic approaches

Assumptions and events

2005

EU approval of liquid Aricept will increase its use in severe AD

EU decision on the use of Namenda in mild to moderate AD

2006

NICE to publish its final guidance on AD drugs

Aricept set to become the first US full-spectrum AD drug

The first transdermal AChEI to be filed

2007

Assessment of xaliproden (Xaprila)

Novartis aims to differentiate with ExelonTDS

2008

AChEI generics enter the US market

2009

A new generation of AD products - Alzhemed launched in the US

Flurizan's US uptake not expected to be as strong as that of Alzhemed

Memantine finally becomes available in Japan

Generic memantine becomes available in Germany and Spain

Razadyne makes its entry in Japan

2010

Alzhemed available for use in Europe

Flurizan launched in the EU

Generic donepezil becomes available in the US

2011

Generic memantine becomes available in the US

The impact of memantine generics may be reduced by neramexane's entry in the US

The last of the AChEIs, Exelon, goes off patent in the US

Generic rivastigmine launches in Germany

2012

Forest launches neramexane across the EU

European AChEIs get hit by generics

Generic rivastigmine launches in France and the UK

The Japanese market washed out as Aricept's patent expires

2013

Generic rivastigmine launches in Italy and Spain

2014

Generic rivastigmine finally becomes available in the US

Generic memantine becomes available in the remaining major EU markets

Case studies

Managing the product lifecycle for maximum revenues

Formulations not yet tested in the AD market

Demonstrating the benefits of combinations can be a source of gains

Phase II drugs may limit the success of Alzhemed and Flurizan

AD market data

Preclinical drug pipeline

Bibliography

AD drug revenue forecasts by country

Report methodology

Standard Units

Japanese Market Data

Derivation of Sales Forecasts and Pricing Trends

Regional Launch Dates for New Products

Generic Erosion and Pricing Assumptions

ABOUT DATAMONITOR

Disclaimer

List of Tables

Table 1: Key parameters of AD

Table 2: Forecast key pipeline products in AD from 2010-14

Table 3: Common clinical features in Alzheimer's disease by stage

Table 4: Prevalence for moderate and severe AD only

Table 5: Population estimates for moderate and severe AD (millions), 1995-2050

Table 6: AD comorbidity trials of existing drugs

Table 7: DSM-IV criteria for Alzheimer's type dementia

Table 8: Diagnosis rates across the seven major markets, 2005

Table 9: Drug-treated AD populations across the seven major markets, 2005

Table 10: Prevalence of Alzheimer's disease by gender and age

Table 11: Prevalence of Alzheimer's disease across the seven major markets, 2005

Table 12: AD population across the seven major markets (millions), 1995-2050

Table 13: Global AD drug revenues, 2004

Table 14: US AD drug market, 2004

Table 15: AD drug market in Japan, 2004

Table 16: AD drug market in France, 2004

Table 17: AD drug market in Germany, 2004

Table 18: AD drug market in Italy, 2004

Table 19: AD drug market in Spain, 2004

Table 20: UK AD drug market, 2004

Table 21: Measures used for clinical efficacy endpoints in AD

Table 22: AD drugs in Phase III clinical development, 2005

Table 23: AD drugs in Phase II clinical development, 2005

Table 24: AD drugs in Phase I clinical development, 2005

Table 25: Eli Lilly's AD pipeline, 2005

Table 26: Sanofi-Aventis's AD pipeline, 2005

Table 27: Axonyx's AD pipeline, 2005

Table 28: Mindset's pipeline, 2005

Table 29: Aâ modulators in late-stage development 2005

Table 30: Global revenue forecasts for Alzhemed, 2005-14

Table 31: Impacting factors on the revenues of Alzhemed, 2005-14

Table 32: Global revenue forecasts for Flurizan, 2005-14

Table 33: Impacting factors on the revenues of Flurizan, 2005-14

Table 34: Discontinued R&D projects in the Beta-Amyloid modulator class, 2004-05

Table 35: Global sales forecasts for Aâ modulator drugs, 2006-14

Table 36: ACh modulators in late-stage development, 2005

Table 37: Discontinued R&D projects in the ACh modulator class, 2004-05

Table 38: NMDA modulators in late-stage development 2005

Table 39: Global sales forecasts for neramexane, 2005-14

Table 40: Impacting factors on the revenues of neramexane, 2005-14

Table 41: Neuroprotectant drugs in late-stage development, 2005

Table 42: Other drugs in late stage development, 2005

Table 43: Aricept key facts

Table 44: Key Aricept events, 2004-2005

Table 45: Razadyne/ Razadyne ER key facts

Table 46: Key Razadyne/ Razadyne ER events, 2004-2005

Table 47: Exelon key facts

Table 48: Namenda key facts

Table 49: Key Namenda events, 2004-2005

Table 50: AD drugs in preclinical development, 2005

Table 51: AD drug comparator score sheet

Table 52: US AD drug revenue forecast

Table 53: Japan AD drug revenue forecast

Table 54: France AD drug revenue forecast

Table 55: Germany AD drug revenue forecast

Table 56: Italy AD drug revenue forecast

Table 57: Spain AD drug revenue forecast

Table 58: UK AD drug revenue forecast

Table 59: EU5 AD drug revenue forecast

Table 60: Global AD drug revenue forecast

List of Figures

Figure 1: AD population across the seven major markets, 1995-2050

Figure 2: Total global quarterly AD drug sales, 1999-2005

Figure 3: Global quarterly AD drug sales, 1999-2005

Figure 4: AD drug share by revenue across the seven major markets, 1999-2005

Figure 5: Key players in the AD market

Figure 6: Importance of unmet needs in AD

Figure 7: AD relative treatment ratios

Figure 8: AD drug market, quarterly revenues, 1999-2005

Figure 9: US AD market share, by revenue, 1999-2005

Figure 10: AD drug market in Japan, quarterly revenues, 1999-2005

Figure 11: AD drug market in France, quarterly revenues, 1999-2005

Figure 12: AD market share in France, by revenue, 1999-2005

Figure 13: AD drug market in Germany, quarterly revenues, 1999-2005

Figure 14: AD market share in Germany, by revenue, 1999-2005

Figure 15: AD drug market in Italy, quarterly revenues, 1999-2005

Figure 16: AD market share in Italy, by revenue, 1999-2005

Figure 17: AD drug market in Spain, quarterly revenues, 1999-2005

Figure 18: AD market share in Spain, by revenue, 1999-2005

Figure 19: AD drug market in the UK quarterly revenues, 1999-2005

Figure 20: AD market share in the UK, by revenue, 1999-2005

Figure 21: AD pipeline drugs in each development stage by class

Figure 22: Alzhemed's satisfaction of unmet needs

Figure 23: Flurizan's satisfaction of unmet needs

Figure 24: Commercial comparison of beta-amyloid modulators Alzhemed and Flurizan against gold standard Aricept

Figure 25: Commercial comparison of NMDA modulator neramexane against gold standard Namenda

Figure 26: Potential impact of Phase II drugs on US forecasts

Figure 27: US forecast for pipeline drugs without Phase II drug impact

Abstract

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