Product Profiles: Alzheimer's Disease - Immunotherapies can revolutionize treatment paradigm

Introduction

The beta-amyloid hypothesis has so far failed to deliver a viable candidate, contributing to an absence of new market entrants over the past decade. However, given the weight of candidates with disease-modifying potential in the pipeline, new drugs are expected to emerge that will satisfy one of the biggest unmet needs in the industry – a treatment that slows Alzheimer’s disease neurodegeneration.

Features and benefits

• Understand Datamonitor’s independent appraisal of marketed brands and key pipeline agents indicated for treating Alzheimer’s disease.
• Illustrate how pipeline and marketed drugs compare to one another in terms of clinical and commercial attributes.
• Review important clinical developments for key pipeline agents with analysis of the latest clinical trial data.
• Understand how marketed brands are positioned in the Alzheimer’s disease treatment algorithm.
• Determine to what extent future therapies satisfy the main clinical unmet needs in Alzheimer’s disease treatment.

Highlights

• Datamonitor’s physician survey reveals that Aricept finds widespread use across all lines of therapy and severities, from mild cognitive impairment to severe Alzheimer’s disease. However, Eisai faces a steep decline in revenues as generic donepezil take hold in the US, marketed competition heightens in Japan, and European patents near expiry.
• Bapineuzumab and solanezumab have the potential to revolutionize Alzheimer’s disease treatment and become future market leaders. However, each program carries a caveat. J&J/Pfizer are relying on post-hoc analyses of bapineuzumab in a subpopulation while Lilly is betting on solanezumab’s Phase II biomarker effect translating into tangible benefits.
• A precedent already exists for neurotransmitter mechanisms, ensuring a higher likelihood of navigating through clinical trials. Late-stage symptomatic drugs include Eisai’s Aricept patch and GSK’s 5-HT6 receptor agonist SB-742457, although the potential rewards on offer for these candidates are lower than for the immunotherapies.

Table Of Contents

OVERVIEW
Catalyst
Summary

EXECUTIVE SUMMARY
Strategic scoping and focus
Datamonitor key findings
Related reports

PRODUCT OVERVIEW
Product Overview

MARKETED PRODUCT PROFILES
Aricept (donepezil; Eisai/Pfizer)
Drug profile
Development overview
SWOT analysis
Product positioning
Clinical and commercial attractiveness
Exelon (rivastigmine; Novartis)
Drug profile
Development overview
SWOT analysis
Product positioning
Clinical and commercial attractiveness
Razadyne (galantamine; Johnson & Johnson/Shire)
Drug profile
Development overview
SWOT analysis
Product positioning
Clinical and commercial attractiveness
Namenda (memantine; Forest/Merz/Lundbeck)
Drug profile
Development overview
SWOT analysis
Product positioning
Clinical and commercial attractiveness

PIPELINE PRODUCT PROFILES
Bapineuzumab (Johnson & Johnson/Pfizer)
Drug profile
Development overview
SWOT analysis
Satisfaction of unmet needs
Clinical and commercial attractiveness
Solanezumab (LY2062430; Eli Lilly)
Drug profile
Development overview
SWOT analysis
Satisfaction of unmet needs
Clinical and commercial attractiveness
Gammagard (intravenous immunoglobulin; Baxter)
Drug profile
Development overview
SWOT analysis
Satisfaction of unmet needs
Clinical and commercial attractiveness
Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku)
Drug profile
Development overview
SWOT analysis
Satisfaction of unmet needs
Clinical and commercial attractiveness
SB-742457 (GlaxoSmithKline)
Drug profile
Development overview
SWOT analysis
Satisfaction of unmet needs
Clinical and commercial attractiveness
Other key disease-modifying drugs in development for Alzheimer’s disease
ACC-001 (conjugate beta-amyloid vaccine; Johnson & Johnson/Pfizer)
AD02 (beta-amyloid vaccine; GlaxoSmithKline/Affiris)
Avagacestat (BMS-708163; Bristol-Myers Squibb)
CAD106 (beta-amyloid vaccine; Novartis/Cytos Biotechnology)
CERE-110 (AAV2-NGF; Ceregene)
CHF5074 (Chiesi Pharmaceuticals)
Crenezumab (R7412/MABT5102A; Roche/AC Immune)
Davunetide (AL-108; Allon Therapeutics)
ELND005 (scyllo-inositol; Elan)
EHT 0202 (etazolate; ExonHit Therapeutics)
Gantenerumab (R1450; Roche/MorphoSys)
Masitinib (AB1010; AB Science)
NIC5-15 (Humanetics)
Nypta (tideglusib; Noscira)
Octagam (intravenous immunoglobulin; Octapharma)
PF-04494700 (Pfizer/TransTech Pharma)
PBT2 (Prana Biotechnology)
Rember (methylthioninium chloride; TauRx Pharmaceuticals)
T-817MA (Toyama Chemical)
Other key symptomatic drugs in development for Alzheimer’s disease
ABT-288 (Abbott Laboratories)
Dimebon (latrepirdine; Pfizer/Medivation)
EVP-6124 (EnVivo Pharmaceuticals)
GSK239512 (GlaxoSmithKline)
Ispronicline (AZD3480; AstraZeneca/Targacept)
Lu AE58054 (Lundbeck)
BIBLIOGRAPHY
Journal papers
Websites
Datamonitor reports

APPENDIX A – SURVEY INFORMATION
Physician research methodology
Physician sample breakdown
The survey questionnaire
Screener
Section 10: Alzheimer’s disease regimens
Section 11: Treated disease stages
Section 12: Treatment flow – mild cognitive impairment due to Alzheimer’s disease
Section 13: Treatment flow – mild Alzheimer’s disease
Section 14: Treatment flow – moderate Alzheimer’s disease
Section 15: Treatment flow – severe Alzheimer’s disease
APPENDIX B
PharmaVitae Explorer database
Datamonitor drug assessment scorecard
Contributing experts
Conferences attended
Report methodology

LIST OF TABLES

Table: Key marketed and pipeline products for Alzheimer’s disease, 2011
Table: Aricept (donepezil; Eisai/Pfizer) – drug profile in Alzheimer’s disease, 2011
Table: Overview of pivotal trial data for Aricept (donepezil; Eisai/Pfizer) in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for Aricept (donepezil; Eisai/Pfizer) in Alzheimer’s disease, 2011
Table: Exelon (rivastigmine; Novartis) – drug profile in Alzheimer’s disease, 2011
Table: Overview of pivotal trial data for Exelon (rivastigmine; Novartis) in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for Exelon (Novartis) in Alzheimer’s disease, 2011
Table: Razadyne (galantamine; Johnson & Johnson/Shire) – drug profile in Alzheimer’s disease, 2011
Table: Overview of pivotal trial data for Razadyne (galantamine; Johnson & Johnson/Shire) in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for Razadyne (galantamine; Johnson & Johnson/Shire) in Alzheimer’s disease, 2011
Table: Namenda (memantine; Forest/Merz/Lundbeck) – drug profile in Alzheimer’s disease, 2011
Table: Overview of pivotal trial data for Namenda (memantine; Forest/Merz/Lundbeck) in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for Namenda in Alzheimer’s disease, 2011
Table: Bapineuzumab (Johnson & Johnson/Pfizer ) – drug profile in Alzheimer’s disease, 2011
Table: Clinical trial summary for bapineuzumab (Johnson & Johnson/Pfizer) in Alzheimer’s disease
Table: Ongoing clinical development program for bapineuzumab (Johnson & Johnson/Pfizer) in Alzheimer’s disease, 2011
Table: Bapineuzumab (Johnson & Johnson/Pfizer) versus comparator therapy Aricept (donepezil; Eisai/Pfizer), the minimum acceptable product profile, and the target product profile in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for bapineuzumab (Johnson & Johnson/Pfizer) in Alzheimer’s disease, 2011
Table: Solanezumab (LY2062430; Eli Lilly ) – drug profile in Alzheimer’s disease, 2011
Table: Ongoing clinical development program for solanezumab (LY2062430; Eli Lilly) in Alzheimer’s disease, 2011
Table: Solanezumab (LY2062430; Eli Lilly) versus comparator therapy Aricept (donepezil; Eisai/Pfizer), the minimum acceptable product profile, and the target product profile in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for solanezumab (Eli Lilly) in Alzheimer’s disease, 2011
Table: Gammagard (intravenous immunoglobulin; Baxter ) – drug profile in Alzheimer’s disease, 2011
Table: Key facts: Phase III trial of Gammagard, 2011
Table: Gammagard (intravenous immunoglobulin; Baxter) versus comparator therapy Aricept (donepezil; Eisai/Pfizer), the minimum acceptable product profile, and the target product profile in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for Gammagard (intravenous immunoglobulin; Baxter) in Alzheimer’s disease, 2011
Table: Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku ) – drug profile in Alzheimer’s disease, 2011
Table: Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku) versus comparator therapy Aricept (donepezil; Eisai/Pfizer), the minimum acceptable product profile, and the target product profile in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for the Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku) in Alzheimer’s disease, 2011
Table: SB-742457 (GlaxoSmithKline ) – drug profile in Alzheimer’s disease, 2011
Table: Clinical trial summary for SB-742457 (GlaxoSmithKline) in Alzheimer’s disease
Table: SB-742457 (GlaxoSmithKline) versus comparator therapy Aricept (donepezil; Eisai/Pfizer), the minimum acceptable product profile, and the target product profile in Alzheimer’s disease, 2011
Table: Datamonitor’s drug assessment scorecard for SB-742457 in Alzheimer’s disease, 2011
Table: ACC-001: ongoing studies for the treatment of Alzheimer’s disease, 2011
Table: Key facts: Phase II trial of AD02 (GlaxoSmithKline/Affiris), 2011
Table: Key facts: Phase II trial of avagacestat (BMS-708163; Bristol-Myers Squibb), 2011
Table: Key facts: Phase II trial of CERE-110, 2011
Table: Key facts: Phase II trial of crenezumab (Roche/AC Immune), 2011
Table: Key facts: Phase II trial of gantenerumab (R1450; Roche/MorphoSys), 2011
Table: Key facts: Phase II trial of Nypta (tideglusib; Noscira), 2011
Table: Key facts: Phase II trial of Octagam, 2011
Table: Key facts: Phase II trial of PF-04494700, 2010
Table: Key facts: Phase II trial of T-817MA, 2011
Table: Key facts: Phase II trial of ABT-288, 2011
Table: Key facts: Phase II trial of EVP-6124, 2011
Table: Key facts: Phase II trial of GSK239512, 2010
Table: Key facts: Phase II trial of Lu AE58054, 2010
Table: Neurologists surveyed regarding Alzheimer’s disease across the seven major markets, 2011
Table: Datamonitor’s drug assessment parameters for key Alzheimer’s disease therapies

LIST OF FIGURES

Figure: Datamonitor’s drug assessment summary for Alzheimer’s disease, 2011
Figure: Aricept (donepezil; Eisai/Pfizer) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Aricept (donepezil; Eisai/Pfizer) use by line of therapy and disease severity in the seven major markets, 2011
Figure: Datamonitor’s drug assessment summary for Aricept (donepezil; Eisai/Pfizer) in Alzheimer’s disease, 2011
Figure: Exelon (rivastigmine; Novartis) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Exelon (rivastigmine; Novartis) use by line of therapy and disease severity in the seven major markets, 2011
Figure: Datamonitor’s drug assessment summary for Exelon (rivastigmine; Novartis) in Alzheimer’s disease, 2011
Figure: Razadyne (galantamine; Johnson & Johnson/Shire) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Razadyne (galantamine; Johnson & Johnson/Shire) use by line of therapy and disease severity in the seven major markets, 2011
Figure: Datamonitor’s drug assessment summary for Razadyne i(galantamine; Johnson & Johnson/Shire) n Alzheimer’s disease, 2011
Figure: Namenda (memantine; Forest/Merz/Lundbeck) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Namenda (memantine; Forest/Merz/Lundbeck) use by line of therapy and disease severity in the seven major markets, 2011
Figure: Datamonitor’s drug assessment summary for Namenda in Alzheimer’s disease, 2011
Figure: Bapineuzumab (Johnson & Johnson/Pfizer) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Datamonitor’s drug assessment summary for bapineuzumab (Johnson & Johnson/Pfizer) in Alzheimer’s disease, 2011
Figure: Solanezumab (LY2062430; Eli Lilly) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Datamonitor’s drug assessment summary for solanezumab (Eli Lilly) in Alzheimer’s disease, 2011
Figure: Phase II Gammagard clinical trial design and results
Figure: Gammagard (intravenous immunoglobulin; Baxter) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Datamonitor’s drug assessment summary for Gammagard (intravenous immunoglobulin; Baxter) in Alzheimer’s disease, 2011
Figure: Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Datamonitor’s drug assessment summary for the Aricept patch (transdermal donepezil; Eisai/Teikoku Seiyaku) in Alzheimer’s disease, 2011
Figure: Phase II SB-742457 dose-ranging trial design and results
Figure: Phase II SB-742457 comparator trial with donepezil design and results
Figure: SB-742457 (GlaxoSmithKline) – SWOT analysis for Alzheimer’s disease, 2011
Figure: Datamonitor’s drug assessment summary for SB-742457 in Alzheimer’s disease, 2011
Figure: Phase II masitinib clinical trial design and results
Figure: Phase II Dimebon clinical trial design and results
Figure: Q12.1 First line treatment of mild cognitive impairment due to Alzheimer’s disease
Figure: Q12.2 Second line treatment of mild cognitive impairment due to Alzheimer’s disease
Figure: Q13.1 First line treatment of mild Alzheimer’s disease
Figure: Q13.2 Second line treatment of mild Alzheimer’s disease
Figure: Q14.1 First line treatment of moderate Alzheimer’s disease
Figure: Q14.2 Second line treatment of moderate Alzheimer’s disease
Figure: Q15.1 First line treatment of severe Alzheimer’s disease
Figure: Q15.2 Second line treatment of severe Alzheimer’s disease
Figure: The PharmaVitae Explorer