Market Report Source

Overview

Introduction
A lack of prescriber adherence to both marketing licenses and pharmacoeconomic guidelines represents both a challenge and opportunity for pharmaceutical companies marketing current Alzheimer’s disease drugs. Indication expansion between disease severities may not be a viable commercial option; conversely, stricter guidelines by bodies such as the UK’s NICE will not necessarily threaten the market.

Scope
Treatment trends of front-line Alzheimer’s disease drug prescribers, based on a survey of 181 neurologists.
Insight into neurologist’s perception of marketed and pipeline drugs according to Datamonitor’s primary research.
Rating of unmet needs in Alzheimer’s disease pharmacotherapy.
In-depth interviews with five key international opinion leaders.

Highlights
Datamonitor’s survey shows that symptomatic improvement is still a high priority, indicating that neurologists would welcome a new non-disease modifying drug if it was differentiated from the current cognitive enhancers on efficacy or side effects. In order to achieve this in the minds of neurologists, an alternative mode of action is required.

Datamonitor forecasts that the introduction of disease modifying drugs (e.g. Alzhemed, Flurizan) will not necessarily threaten the acetylcholine esterase inhibitor market, in fact, treatment with such drugs will extend the therapeutic window for symptomatic drugs, resulting in an opportunity for key players in this market.

Datamonitor believes that the recently published NICE guidelines will only have a modest impact on Alzheimer’s disease drug sales in the UK. From looking at survey reported current prescribing trends and relating this to adherence with previous NICE Alzheimer’s disease drug guidelines, prescribers do not appear to guideline-prescribe.

Reasons to Purchase
Understand differential treatment and unmet needs in different disease severities.
Benchmark brand awareness and neurologists perceptions surrounding product positioning in order to formulate lifecycle management strategies.
Validate new product forecasting based on diagnosis and treatment rates, and the likely rate of uptake for new products.

Table of Contents

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the Alzheimer’s disease market

CHAPTER 2 INTRODUCTION AND SCOPE

Coverage of the Stakeholder Insight Survey

Disease definition & epidemiology

Diagnosis

Key prescribing influences

CHAPTER 3 COUNTRY TREATMENT TREES

Country treatment trees

CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION

Definition of Alzheimer’s disease

Etiology

Beta-amyloid hypothesis

Tau neurofibrillary tangles

Neuronal death caused by beta-amyloid deposition and neurofibrillary tangles

Prevalence of Alzheimer’s disease and other dementias

Literature-reported Alzheimer’s prevalence rates

US AD population

EU5 and Japan AD populations

Comparison with other reported AD prevalence rates

Datamonitor survey reported Alzheimer’s disease prevalence rates

Factors influencing prevalence

Age and gender

Patients most frequently presented for the first time in the 70-79 age group

Genetics

Prevalence rates of Mild Cognitive Impairment and other dementias

Neurologists reported similar prevalence rates of Mild Cognitive Impairment and Alzheimer’s disease

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

Off-label prescribing for MCI constitutes approximately 6% of acetyl cholinesterase inhibitors sales in the seven major markets

Progression of MCI to Alzheimer’s disease

Segmentation of Alzheimer’s disease

Clinical features of Alzheimer’s disease severity subtypes

Mild AD affects memory, language and reasoning

Moderate AD demonstrates more pronounced symptoms

Severe AD leaves patients completely dependent

Prescribers may not regard the segmentation of AD into severities as clinically significant

Patients are generally categorized as suffering from moderate AD for the longest period of the disease progression

Clinical definition and features of each AD severity

Prevalence of Alzheimer’s disease severity subtypes

Co-morbidities

A large proportion of the AD population suffer from co-morbidities

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

CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS

Presentation and diagnosis

Diagnosis techniques – many hopes on the horizon, but current practices have not developed much in the last 100 years

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

Time to presentation

Time to presentation may seem long, but KOLs were unconcerned

It is in pharmaceutical companies’ interests to decrease this time by increasing awareness

Significant reduction in time to presentation only possible following development of more advanced diagnostic tools

The future – biomarkers

Time to correct diagnosis

Treatment options

Non-pharmacological treatment is still a commonly used option for AD therapy

Pharmacological treatment

Acetylcholinesterase inhibitors

NMDA receptor antagonist: Memantine (Namenda/Ebixa/Axura)

Non-pharmacological treatment

Treatment guidelines

UK – National Institute of Clinical Excellence (NICE) guidelines

NICE guidelines for AD

NICE guidelines are for the UK NHS only, but may have further reaching implications

How could NICE guidelines directly impact AD drug sales in the UK?

Treatment of cognitive symptoms with AChEIs only recommended for moderate severity AD patients

It is still advised that mild and severe severity AD patients with non-cognitive symptoms receive AChEIs

Choice of AChEIs

If cost-benefit analysis had been conducted on the actual cost paid by PCTs, the AChEIs could be cost-effective

NICE only considers the direct cost to the NHS, if costs to individuals and social services had been appreciated, the cost-benefit balance may have been different

Memantine not recommended for AD treatment of any severity

An evaluation of AChEI/memantine combination therapy would more closely reflect treatment regimes

NICE recommend continuation of therapy for patients currently receiving treatment

Datamonitor’s view on the direct effect of these NICE guidelines on sales revenue

Can an estimate of future prescribing trends post-NICE recommendations be made from past prescribing?

Germany – Institute for Quality and Efficiency (IQWiG)

American Academy of Neurology guidelines

Other guidelines in the seven major market

Referral patterns

CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS

Prescribing trends

Prescribing trends caveats

Role of pharmacological treatment in the management of AD

Progression from first- to second-line therapy consistent across disease severity

Higher percentage of pharmacological treatment for severe AD patients than mild AD patients would seem contradictory to clinical benefit

Pharmacological treatment of severe AD patients particularly high in relation to mild AD patients in the UK

Pharmacological treatment of moderate AD patients higher in the US than the EU5

Companies marketing AD drugs should concentrate resources on the treatment of mild AD patients in the six major markets outside of the US

Seven major market overview of prescribing trends for AD

Overview of treatment paradigms for AD patients

Eisai’s and Pfizer’s donepezil (Aricept) is the clear market leader in AD treatment

What is first- and second-line AD treatment?

Memantine is used more frequently in combination with an AChEI than as a monotherapy in moderate and severe AD patients

Use of combination therapy as a first-line treatment increases through the disease progression

First- to second-line progression

Approximately one-quarter of pharmacologically treated patients move to second-line treatment when first-line treatment has failed

Second-line therapy consists of either adding memantine to the treatment regime, or switching patients to another AChEI

Increased use of AChEI + memantine combination treatment in second-line therapy

Neurologists not prescribing combination therapy first-line for mild severity AD patients, prescribe it as a second-line therapy

More mild severity AD patients treated by neurologists that do not prescribe AChEI and memantine combination therapy move to second-line therapy

Neurologists that do not prescribe mild severity AD patients combination therapy first-line, do prescribe this treatment regime for moderate and severe patients

Lundbeck/Forest should attempt to stimulate prescribing of memantine first-line, especially in mild AD patients

Off-label prescribing in the AD market

Neurologists reported that off-label prescribing of the AChEIs and memantine represents approximately one-fifth of total prescribing

Beyond other unlicensed disease severities, what are AChEIs and memantine used for off-label?

Factors influencing physician decision making

Neurologists report efficacy based factors are the primary considerations when prescribing AD drugs

Symptomatic improvement is still a high priority

Neurologists would welcome a new non-disease modifying drug if it was differentiated from the AChEIs

Neurologists regard the introduction of a disease modifying drug as critical in the longer term

Side-effect profile is the most important non-efficacy related factor considered by neurologists when prescribing AD drugs

Reimbursement status, formulary inclusion and cost effectiveness are the least considered factors by neurologists when prescribing AD drugs

Scenarios for future AD treatment paradigms, patient prognosis and the AChEI market

Datamonitor believe that the introduction of disease modifying drugs will not threaten AChEI sales

Diagram A – Untreated AD patient

Diagram B – AD patient prescribed an AChEI (and/or memantine)

Diagram C – AD patient prescribed ideal disease slowing drug

Diagram D – AD patient prescribed efficacious disease slowing drug

Diagram E – AD patient prescribed ideal disease slowing drug and cognitive enhancer (e.g. AChEI)

Diagram F – AD patient prescribed efficacious disease modifying drug and cognitive enhancer

Diagram G – AD patient prescribed ideal disease slowing/disease modifying drug diagnosed before cognitive decline with a biomarker

Diagram H – AD patient prescribed ideal disease modifying drug

Late-stage disease modifying drugs aim to attenuate the production of ‘toxic’ beta-amyloid

Alzhemed

Clinical trials investigating the efficacy of Alzhemed

Flurizan

Phase III trials investigating Flurizan currently underway

Phase II studies

Neurologists perception of marketed and pipeline drugs

Datamonitor has used a brand map to show the significance of neurologists’ perception of the marketed and pipeline drugs

Interpreting Datamonitor’s AD brand map

Datamonitor’s brand map shows a clear differentiation between the three classes of AD drug

Symptomatic improvement characteristic defines the AChEI class of drug

Memantine’s side-effect profile differentiates it from other classes of AD drugs

Neurologists believe that the beta-amyloid modifying pipeline drugs will prove to be disease modifying by slowing disease progression

Indication expansion

Donepezil (Aricept) for severe Alzheimer’s patients

Due to off-label prescribing, the severe severity AD market may already be saturated

Donepezil’s (Aricept) number one position in the AD market will be secured following this license

Reformulation strategies

Launch of liquid donepezil (Aricept)

Generic incursion

Neurologists’ perceptions of generic uptake

Reduced cost, increased use?

CHAPTER 7 IMPROVING TREATMENT OUTCOMES

Treatment outcomes

Patient response to current treatment is modest

Reason for discontinuing therapy

Lack of efficacy and intolerable side effects are the leading reasons for treatment discontinuation

Unmet needs

Overview of neurologist weighted unmet needs

Improved efficacy of treatment remains the most important clinical unmet need

Improved side effect profile of treatments is imperative given the overall health of the many AD patients

Cost is an issue because of a general move towards pharmacoeconomic evaluations and the potential arrival of new treatments

BIBLIOGRAPHY

Journals

Websites

Datamonitor reports

APPENDIX A

Physician research methodology

Physician sample breakdown

Contributing experts

APPENDIX B

THE SURVEY QUESTIONNAIRE

Epidemiology, presentation and diagnosis of Alzheimer’s disease

Treatment of Alzheimer’s disease

Treatment of mild Alzheimer’s disease

Treatment of moderate Alzheimer’s disease

Treatment of severe Alzheimer’s disease

Current and future treatment of Alzheimer’s disease

Key prescribing factors

Unmet Needs

Disclaimer