Atopic Dermatitis A high level of unmet need creates market opportunities
About the Immune Disorders and
Inflammation (IDI) pharmaceutical analysis team
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CHAPTER 1 EXECUTIVE SUMMARY
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Scope of the report
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Objective of the analysis
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Datamonitor insight into the atopic dermatitis market
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CHAPTER 2 INTRODUCTION AND EPIDEMIOLOGY
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Classification of atopic dermatitis
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Atopic dermatitis is a chronic, relapsing skin disease and has many clinical
features
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Atopic dermatitis occurs in three distinct clinical phases: infantile, childhood
and adult
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Segmenting the AD population
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Assessing disease severity in AD can be problematic
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Patients are segmentated according to mild, moderate and severe atopic
dermatitis
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There is no single way of assessing disease severity
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Will there ever be a single standardized index to assess disease severity?
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Atopic dermatitis significantly affects quality of life
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Pathophysiology of atopic dermatitis
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There is an acute and chronic phase involved in the pathogenesis of atopic
dermatitis
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Atopic dermatitis is driven by T cells and specific cytokines
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Phosphodiesterase IV hyperactivity is thought to be a feature of atopic
dermatitis
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Epidemiology of atopic dermatitis
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Atopic dermatitis has both genetic and environmental risk factors
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Family history remains the strongest predictor for the development of atopic
dermatitis
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Environmental factors play a major role in atopic dermatitis
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Atopic dermatitis affects females slightly more than males
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The prevalence of atopic dermatitis has risen in the past three decades
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Comparing epidemiological studies is a challenge
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There are around 40 million patients with atopic dermatitis in the seven major
markets
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US
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Japan
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Europe
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CHAPTER 3 UNMET NEEDS
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Introduction
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Unmet medical needs in atopic dermatitis
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Patient education is seen as critical by opinion leaders
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Standardized treatment regimens and patient education will help improve
compliance
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How can pharmaceutical companies help with patient education?
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Tackling the itch: more drugs are needed to specifically target pruritus
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Lack of treatment options for severe atopic dermatitis
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Preventative strategies will become increasingly important
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There is another unmet need for less expensive therapies
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Providing therapies for the infant population
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Identifying the processes involved in lichenification
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Summary of unmet needs
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CHAPTER 4 CURRENT TREATMENTS FOR ATOPIC DERMATITIS
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Treatment overview
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Datamonitor's definition of atopic dermatitis
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Size of the atopic dermatitis market
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Non-pharmacological therapy
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Combination of behavioral modification techniques with topical therapies reduces
scratching associated with atopic dermatitis
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UV phototherapy can be an effective treatment option but is limited to adult
sufferers or severe cases of atopic dermatitis
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Emollients reduce the symptoms of dry skin and can reduce the need for topical
corticosteroid treatment
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Pharmacological therapy
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Topical corticosteroids remain the cornerstone of treatment for atopic
dermatitis
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The arrival of topical calcineurin inhibitors represented a significant advance
in the treatment options for atopic dermatitis
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Combination of topical therapies can accelerate remission of atopic dermatitis
and helps to lessen the risk of side effects
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Antihistamines are used to treat pruritus but their efficacy remains
questionable
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Tricyclic antidepressants, such as doxepin hydrochloride, can be prescribed to
promote restful sleep and tackle pruritus
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Systemic and topical antibiotics are prescribed in order to counteract secondary
bacterial infections associated with atopic dermatitis
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Systemic corticosteroids should be avoided unless they are required for acute
flare-ups in severe atopic dermatitis
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A number of immunosuppresive drugs, including cyclosporin A and mycophenolate
mofetil, are used off-label to treat atopic dermatitis
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CHAPTER 5 TREATMENT CONTROVERSIES
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Patient's phobia of corticostoids can lead to non-compliance and ultimately to
treatment failure
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The long-term safety of topical calcineurin inhibitors has been questioned
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The FDA imposed a black box warning for Protopic and Elidel
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The black box warning was based on theoretical risk and not on clinical evidence
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The FDA's decision limits the availability of TCIs and pushes patients back on
to topical corticosteroids or on to more harmful systemic drugs
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Safety concerns and black box warning have impacted on the sales of Elidel and
Protopic in the US, 5EU and Japan
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In Europe, the EMEA reviewed the safety data of Protopic and Elidel and
concluded the benefits outweigh the risks
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Most clinical trials to date suggest a favorable safety profile for topical
calcineurin inhibitors
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An oral formulation of pimecrolimus has been discontinued by Novartis
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Cost of topical calcineurin inhibitors is high
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In general TCIs are 20 times more expensive than corticosteroids
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Topical calcineurin inhibitors cost nearly twice as much in the US than in the
UK
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Cream versus ointment: what type of topical formulation is most appropriate for
atopic dermatitis?
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In the US and 5EU, creams are the most popular formulation of topcial
corticosteroid, however, ointments are more popular in Japan
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Ointments are more effective than creams, but creams are preferred for cosmetic
reasons
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Pressure foam preparations are becoming more popular for dermatoses
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Novartis was looking to expand the Elidel product range with an ointment
formulation
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Protopic cream is in late-stage clinical development
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Marketing strategies for topical calcineurin inhibitors
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Fujisawa and GSK joined forces to co-promote Protopic in the US in light of
increased competition from Novartis' Elidel
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Protopic and the Eczema Beast
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Despite being the second topical calcineurin inhibitor to market, sales of
Elidel were double those of Protopic within two years after launch
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Novartis signed co-marketing agreements with Esteve in Spain and 3M in Germany
for pimecrolimus
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Protopic and Elidel are prescribed off-label in a number of dermatological
diseases
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Around 40% of Elidel and Protopic sales are for off-label indications
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The psoriasis market is an attractive prospect but current safety fears may
limit potential
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CHAPTER 6 PIPELINE DRUGS
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The atopic dermatitis pipeline lacks innovative drugs in Phase III
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There are only two drugs in Phase III development for atopic dermatitis
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The majority of drugs in development for atopic dermatitis are topically
administered
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Biologics used in psoriasis are undergoing clinical trials for atopic dermatitis
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Raptiva (efalizumab) is being evaluated as an alternative to systemic
immunosuppressive agents in severe atopic dermatitis
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The immunopharmacological effects of Rituxan/MabThera (rituximab) in atopic
dermatitis are being investigated in a Phase I study
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Amevive (alefacept), the first biologic developed for psoriasis, is in Phase II
for atopic dermatitis
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Is there potential for other psoriasis therapies to expand into the atopic
dermatitis indication?
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High cost of biologicals may be an issue with in atopic dermatitis as it is in
psoriasis
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Histamine may not be a justifiable target for pharmacological intervention
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Topical patch will be interesting for localized disease but not for widely
affected areas
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Protease inhibitors will have a place in the treatment of atopic dermatitis but
remain in Phase II development
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With a promising portfolio, which includes Sabarep for atopic dermatitis, York
Pharma aims to be a force in the field of dermatology
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Arriva's and ProMetic's topical rAAT gel may require reformulation for atopic
dermatitis
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Cytos Biotechnology are aiming to provide a more effective immunotherapy than
those that are currently available
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Early-stage treatments for atopic dermatitis are directed against a variety of
targets
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Cytokines and NF-KappaB modulators
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Topical PDE IV inhibitors
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CHAPTER 7 APPENDIX
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Contributing experts
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Market Profile: Protopic (tacrolimus) and Elidel (pimecrolimus)
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Methodology
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Calculation of 2006 sales figures
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Datamonitor's definition of vitiligo, psoriasis, seborrheic dermatitis and
contact dermatitis
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Bibliography
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Journal articles
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Websites
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Datamonitor reports
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About Datamonitor
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About Datamonitor Healthcare
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Datamonitor Healthcare's research and analysis methodologies
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Datamonitor Healthcare's therapy area capabilities
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Disclaimer
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List of Tables
Table 1: Clinical features of atopic dermatitis
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Table 2: Criteria for the diagnosis of atopic dermatitis
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Table 3: Prevalence studies for atopic dermatitis in the seven major markets,
1994-2004
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Table 4: Datamonitor's estimation of the atopic dermatitis population (000s) in
the seven major markets, 2007
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Table 5: Estimated AD population in the US, 2007
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Table 6: Estimated AD population in Japan, 2007
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Table 7: Estimated AD population in France, 2007
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Table 8: Estimated AD population in Germany, 2007
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Table 9: Estimated AD population in the UK, 2007
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Table 10: Estimated AD population in Spain, 2007
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Table 11: Estimated AD population in Italy, 2007
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Table 12: Examples of available therapies for atopic dermatitis, 2007
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Table 13: Datamonitor's definition of atopic dermatitis according to ICD10 code
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Table 14: Key facts: topical calcineurin inhibitors for atopic dermatitis, 2007
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Table 15: Antihistamines used in the management of atopic dermatitis
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Table 16: Cost of Protopic (tacrolimus) and Elidel (pimecrolimus) in the UK,
2007
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Table 17: Cost of Protopic (tacrolimus) and Elidel (pimecrolimus) in the US
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Table 18: Pipeline products in all stages of development for atopic dermatitis,
2007
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Table 19: Market profile: Protopic (tacrolimus) and Elidel (pimecrolimus), 2007
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Table 20: Datamonitor's definition of vitiligo, psoriasis, seborrheic dermatitis
and contact dermatitis according to ICD10 codes
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List of Figures
Figure 1: Pathogenesis of atopic dermatitis
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Figure 2: Datamonitor's estimation of the atopic dermatitis population (000s) in
the seven major markets, 2007
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Figure 3: Rationale behind the development of antipruritic drugs for AD
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Figure 4: Summary of unmet medical needs in the atopic dermatitis market, 2007
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Figure 5: The atopic dermatitis market, 2005
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Figure 6: Common topical corticosteroids used to treat atopic dermatitis grouped
by strength
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Figure 7: The mechanism of action of topical calcineurin inhibitors
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Figure 8: Topical treatment paradigm for atopic dermatitis
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Figure 9: The FDA black box warning that appears as part of the label change for
Protopic and Elidel, January 2006
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Figure 10: AD-specific sales of Protopic (tacrolimus) in the US, 5EU and Japan
($m), 2005-06
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Figure 11: AD-specific sales of Elidel (pimecrolimus) in the US and 4EU ($m),
2005-06
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Figure 12: Year-on-year sales growth of Protopic and Elidel in the seven major
markets (%), 2003-06
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Figure 13: Sales of topical corticosteroids for all therapeutic indications
categorized by formulation ($m), 2005
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Figure 14: Sales of pressure foam corticosteroids in the US and 5EU by brand for
all therapeutic indications ($m), 2005-06
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Figure 15: Total promotional spend for Elidel and Protopic in the US only ($m),
2003
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Figure 16: Astellas' DTC campaign for Protopic featured the Eczema Beast
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Figure 17: Example of DTC advertising for Novartis' Elidel
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Figure 18: Elidel and Protopic sales in the seven major markets for atopic
dermatitis and off-label indications ($m), 2005
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Figure 19: Pipeline drugs for atopic dermatitis categorized by phase of
development, 2007
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Figure 20: Pipeline drugs for atopic dermatitis categorized by method of
administration, 2007
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Figure 21: Molecular targets for therapies in Phase I and preclinical
development for atopic dermatitis, 2007
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