Market Report Source

Overview

Introduction

Atopic dermatitis is a skin disorder characterized by intense itch, dry skin and redness. Often considered a benign disease, it actually impacts very negatively on quality of life, sometimes more than psoriasis and diabetes. Through opinion leader interviews, Datamonitor has identified a high level of unmet need in atopic dermatitis treatment and believe that a number of market opportunities exist

Scope

• Understand opinion leaders’ views on hot issues in the atopic dermatitis market
• Assess the key unmet medical needs and identify specific opportunities in the atopic dermatitis market
• Examine epidemiological data for the prevalence of atopic dermatitis in the seven major markets (US, Japan, France, Germany, Italy, Spain, UK)
• Explore the current atopic dermatitis pipeline and identify leading products in development

Highlights

About 40 million patients suffer from atopic dermatitis in the seven major markets. There is a high level of unmet need and market opportunities exist for safer systemic therapies and effective drugs for itch. However, high drug cost will be a significant barrier to entry to the market and companies must also increase focus on patient education. Future entrants to the atopic dermatitis market will benefit from the strategies used by Novartis for Elidel such as a rapid global rollout and broad marketing campaign. Approval across all possible patient segments will ensure greatest sales potential. Choice of topical formulation is another important issue that companies must address. The late stage atopic dermatitis pipeline is empty and lacks innovation. In contrast, there are a number of Phase II products looking to fill the gap in the market for effective non-steroidal therapies, left by Protopic and Elidel. Despite a need for systemic therapies, Datamonitor expects the overall demand for topical therapies will remain high.

Reasons to Purchase

• Review available treatments and understand major treatment controversies such as the safety of topical calcineurin inhibitors
• Identify opportunities in the atopic dermatitis market and learn which strategies should be considered for success of future market entrants
• Gain insight into the direction of future research for atopic dermatitis and learn what opinion leaders think of current pipeline products

Table of Contents

About the Immune Disorders and Inflammation (IDI) pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the report

Objective of the analysis

Datamonitor insight into the atopic dermatitis market

CHAPTER 2 INTRODUCTION AND EPIDEMIOLOGY

Classification of atopic dermatitis

Atopic dermatitis is a chronic, relapsing skin disease and has many clinical features

Atopic dermatitis occurs in three distinct clinical phases: infantile, childhood and adult

Segmenting the AD population

Assessing disease severity in AD can be problematic

Patients are segmentated according to mild, moderate and severe atopic dermatitis

There is no single way of assessing disease severity

Will there ever be a single standardized index to assess disease severity?

Atopic dermatitis significantly affects quality of life

Pathophysiology of atopic dermatitis

There is an acute and chronic phase involved in the pathogenesis of atopic dermatitis

Atopic dermatitis is driven by T cells and specific cytokines

Phosphodiesterase IV hyperactivity is thought to be a feature of atopic dermatitis

Epidemiology of atopic dermatitis

Atopic dermatitis has both genetic and environmental risk factors

Family history remains the strongest predictor for the development of atopic dermatitis

Environmental factors play a major role in atopic dermatitis

Atopic dermatitis affects females slightly more than males

The prevalence of atopic dermatitis has risen in the past three decades

Comparing epidemiological studies is a challenge

There are around 40 million patients with atopic dermatitis in the seven major markets

US

Japan

Europe

CHAPTER 3 UNMET NEEDS

Introduction

Unmet medical needs in atopic dermatitis

Patient education is seen as critical by opinion leaders

Standardized treatment regimens and patient education will help improve compliance

How can pharmaceutical companies help with patient education?

Tackling the itch: more drugs are needed to specifically target pruritus

Lack of treatment options for severe atopic dermatitis

Preventative strategies will become increasingly important

There is another unmet need for less expensive therapies

Providing therapies for the infant population

Identifying the processes involved in lichenification

Summary of unmet needs

CHAPTER 4 CURRENT TREATMENTS FOR ATOPIC DERMATITIS

Treatment overview

Datamonitor’s definition of atopic dermatitis

Size of the atopic dermatitis market

Non-pharmacological therapy

Combination of behavioral modification techniques with topical therapies reduces scratching associated with atopic dermatitis

UV phototherapy can be an effective treatment option but is limited to adult sufferers or severe cases of atopic dermatitis

Emollients reduce the symptoms of dry skin and can reduce the need for topical corticosteroid treatment

Pharmacological therapy

Topical corticosteroids remain the cornerstone of treatment for atopic dermatitis

The arrival of topical calcineurin inhibitors represented a significant advance in the treatment options for atopic dermatitis

Combination of topical therapies can accelerate remission of atopic dermatitis and helps to lessen the risk of side effects

Antihistamines are used to treat pruritus but their efficacy remains questionable

Tricyclic antidepressants, such as doxepin hydrochloride, can be prescribed to promote restful sleep and tackle pruritus

Systemic and topical antibiotics are prescribed in order to counteract secondary bacterial infections associated with atopic dermatitis

Systemic corticosteroids should be avoided unless they are required for acute flare-ups in severe atopic dermatitis

A number of immunosuppresive drugs, including cyclosporin A and mycophenolate mofetil, are used off-label to treat atopic dermatitis

CHAPTER 5 TREATMENT CONTROVERSIES

Patient’s phobia of corticostoids can lead to non-compliance and ultimately to treatment failure

The long-term safety of topical calcineurin inhibitors has been questioned

The FDA imposed a black box warning for Protopic and Elidel

The black box warning was based on theoretical risk and not on clinical evidence

The FDA’s decision limits the availability of TCIs and pushes patients back on to topical corticosteroids or on to more harmful systemic drugs

Safety concerns and black box warning have impacted on the sales of Elidel and Protopic in the US, 5EU and Japan

In Europe, the EMEA reviewed the safety data of Protopic and Elidel and concluded the benefits outweigh the risks

Most clinical trials to date suggest a favorable safety profile for topical calcineurin inhibitors

An oral formulation of pimecrolimus has been discontinued by Novartis

Cost of topical calcineurin inhibitors is high

In general TCIs are 20 times more expensive than corticosteroids

Topical calcineurin inhibitors cost nearly twice as much in the US than in the UK

Cream versus ointment: what type of topical formulation is most appropriate for atopic dermatitis?

In the US and 5EU, creams are the most popular formulation of topcial corticosteroid, however, ointments are more popular in Japan

Ointments are more effective than creams, but creams are preferred for cosmetic reasons

Pressure foam preparations are becoming more popular for dermatoses

Novartis was looking to expand the Elidel product range with an ointment formulation

Protopic cream is in late-stage clinical development

Marketing strategies for topical calcineurin inhibitors

Fujisawa and GSK joined forces to co-promote Protopic in the US in light of increased competition from Novartis’ Elidel

Protopic and the Eczema Beast

Despite being the second topical calcineurin inhibitor to market, sales of Elidel were double those of Protopic within two years after launch

Novartis signed co-marketing agreements with Esteve in Spain and 3M in Germany for pimecrolimus

Protopic and Elidel are prescribed off-label in a number of dermatological diseases

Around 40% of Elidel and Protopic sales are for off-label indications

The psoriasis market is an attractive prospect but current safety fears may limit potential

CHAPTER 6 PIPELINE DRUGS

The atopic dermatitis pipeline lacks innovative drugs in Phase III

There are only two drugs in Phase III development for atopic dermatitis

The majority of drugs in development for atopic dermatitis are topically administered

Biologics used in psoriasis are undergoing clinical trials for atopic dermatitis

Raptiva (efalizumab) is being evaluated as an alternative to systemic immunosuppressive agents in severe atopic dermatitis

The immunopharmacological effects of Rituxan/MabThera (rituximab) in atopic dermatitis are being investigated in a Phase I study

Amevive (alefacept), the first biologic developed for psoriasis, is in Phase II for atopic dermatitis

Is there potential for other psoriasis therapies to expand into the atopic dermatitis indication?

High cost of biologicals may be an issue with in atopic dermatitis as it is in psoriasis

Histamine may not be a justifiable target for pharmacological intervention

Topical patch will be interesting for localized disease but not for widely affected areas

Protease inhibitors will have a place in the treatment of atopic dermatitis but remain in Phase II development

With a promising portfolio, which includes Sabarep for atopic dermatitis, York Pharma aims to be a force in the field of dermatology

Arriva’s and ProMetic’s topical rAAT gel may require reformulation for atopic dermatitis

Cytos Biotechnology are aiming to provide a more effective immunotherapy than those that are currently available

Early-stage treatments for atopic dermatitis are directed against a variety of targets

Cytokines and NF-KappaB modulators

Topical PDE IV inhibitors

CHAPTER 7 APPENDIX

Contributing experts

Market Profile: Protopic (tacrolimus) and Elidel (pimecrolimus)

Methodology

Calculation of 2006 sales figures

Datamonitor’s definition of vitiligo, psoriasis, seborrheic dermatitis and contact dermatitis

Bibliography

Journal articles

Websites

Datamonitor reports

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s research and analysis methodologies

Datamonitor Healthcare’s therapy area capabilities

Disclaimer

List of Tables

Table 1: Clinical features of atopic dermatitis

Table 2: Criteria for the diagnosis of atopic dermatitis

Table 3: Prevalence studies for atopic dermatitis in the seven major markets, 1994-2004

Table 4: Datamonitor’s estimation of the atopic dermatitis population (000s) in the seven major markets, 2007

Table 5: Estimated AD population in the US, 2007

Table 6: Estimated AD population in Japan, 2007

Table 7: Estimated AD population in France, 2007

Table 8: Estimated AD population in Germany, 2007

Table 9: Estimated AD population in the UK, 2007

Table 10: Estimated AD population in Spain, 2007

Table 11: Estimated AD population in Italy, 2007

Table 12: Examples of available therapies for atopic dermatitis, 2007

Table 13: Datamonitor’s definition of atopic dermatitis according to ICD10 code

Table 14: Key facts: topical calcineurin inhibitors for atopic dermatitis, 2007

Table 15: Antihistamines used in the management of atopic dermatitis

Table 16: Cost of Protopic (tacrolimus) and Elidel (pimecrolimus) in the UK, 2007

Table 17: Cost of Protopic (tacrolimus) and Elidel (pimecrolimus) in the US

Table 18: Pipeline products in all stages of development for atopic dermatitis, 2007

Table 19: Market profile: Protopic (tacrolimus) and Elidel (pimecrolimus), 2007

Table 20: Datamonitor’s definition of vitiligo, psoriasis, seborrheic dermatitis and contact dermatitis according to ICD10 codes

List of Figures

Figure 1: Pathogenesis of atopic dermatitis

Figure 2: Datamonitor’s estimation of the atopic dermatitis population (000s) in the seven major markets, 2007

Figure 3: Rationale behind the development of antipruritic drugs for AD

Figure 4: Summary of unmet medical needs in the atopic dermatitis market, 2007

Figure 5: The atopic dermatitis market, 2005

Figure 6: Common topical corticosteroids used to treat atopic dermatitis grouped by strength

Figure 7: The mechanism of action of topical calcineurin inhibitors

Figure 8: Topical treatment paradigm for atopic dermatitis

Figure 9: The FDA black box warning that appears as part of the label change for Protopic and Elidel, January 2006

Figure 10: AD-specific sales of Protopic (tacrolimus) in the US, 5EU and Japan ($m), 2005-06

Figure 11: AD-specific sales of Elidel (pimecrolimus) in the US and 4EU ($m), 2005-06

Figure 12: Year-on-year sales growth of Protopic and Elidel in the seven major markets (%), 2003-06

Figure 13: Sales of topical corticosteroids for all therapeutic indications categorized by formulation ($m), 2005

Figure 14: Sales of pressure foam corticosteroids in the US and 5EU by brand for all therapeutic indications ($m), 2005-06

Figure 15: Total promotional spend for Elidel and Protopic in the US only ($m), 2003

Figure 16: Astellas’ DTC campaign for Protopic featured the Eczema Beast

Figure 17: Example of DTC advertising for Novartis’ Elidel

Figure 18: Elidel and Protopic sales in the seven major markets for atopic dermatitis and off-label indications ($m), 2005

Figure 19: Pipeline drugs for atopic dermatitis categorized by phase of development, 2007

Figure 20: Pipeline drugs for atopic dermatitis categorized by method of administration, 2007

Figure 21: Molecular targets for therapies in Phase I and preclinical development for atopic dermatitis, 2007