`
`
`
`
`
`
`) DATAMON ITOR
`
`COMMERCIAL SERIES
`
`Pipeline and Commercial Insight:
`Allergic Rhinitis
`
`Immunotherapy growth surpassed by generic erosion
`
`Reference Code: DMHC2640
`Publication Date: 07/2010
`
`OVERVIEW
`
`Catalyst
`
`Key patent expiries are forecast to shrink the allergic rhinitis market over the next ten years. The only class forecast to grow
`
`is immunotherapy Vlfith significant change seen in clinical development, immunotherapy is attracting increasing attention,
`and is the center of innovation in allergic rhinitis.
`
`Summary
`
`-
`
`-
`
`-
`
`-
`
`Datamonitor estimates that the allergic rhinitis market reached $5 billion in the seven major markets in 2009, and
`forecasts that it will drop to $4 billion by 2019, with patent expiries having the greatest impact on the market;
`
`The role of immunotherapy in allergic rhinitis is increasing as new regulations drive development Vlfith numerous
`products in the pipeline the immunotherapy market is set to experience significant growth, and Datamonitor
`forecasts two key late-stage sublingual immunotherapy tablets;
`
`Datamonitor identified two nasal antihistamins/corticosteroid combinations in late-stage development for allergic
`rhinitis, the first of which, Meda Pharma’s azelastine/fluticasone, is forecast to reach the US market in 2012 and the
`
`EU in 2013, introducing a new treatment option for severe patients;
`
`Coverage: Seven major markets (US, Japan, France, Germany, Italy, Spain, and the UK)
`
`www.datamonitor.com
`Datamonitor America
`Datamonitor Eu rope
`Datamonitor Asia Pacific
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`e: jpinfo@datamonitor.oom
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`HIGHLY CONFIDENTIAL -
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`ME DA_APTX03502401
`CIP2048
`Argentum Pharmaceuticals LLC v. Cipla Ltd.
`lPR2017-00807
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`PTX0396-00001
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`

`

`About Datamonitor Healthcare
`
`) DATA M 0 N ITO R
`
`ABOUT DATAMONITOR HEALTHCARE
`
`Datamonitor Healthcare provides a total business solution to the pharmaceutical and healthcare industries. Its services
`reflect its expertise in therapeutic, strategic and eHealth market analysis and competitive intelligence. For more details of
`Datamonitor Healthcare’s syndicated and customized products and services, please refer to the Appendix or contact:
`
`Bomadata (Bonnie) Bain PhD, Director of Research and Analysis, +1 617 722 4606 :bbain@datamonitor.com
`
`About the Immunology & Inflammation pharmaceutical analysis team
`
`Datamonitor’s therapeutic area studies comprise the following features:
`
`clinical opinion leader intelligence and best»in»class case studies, leading to actionable recommendations;
`
`R&D pipeline and unmet need analysis;
`
`.
`
`scenario-based revenue and epidemiology forecasting;
`
`a slide pack and a data pack.
`
`The Immunology & Inflammation team is headed by Clare Davies (MEng). Clare has experience in the field of market
`research in a range of autoimmune and inflammatory disease areas, and holds a Masters degree in Biochemical
`Engineering from University College London. Clare
`can
`be
`contacted on +44 (0)20 7551
`9023 and
`at
`odavies@datamonitor.com.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHCZ640I Published 07/2010
`
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`

`

`Executive Summary
`
`) DATA M 0 N ITO R
`
`EXECUTIVE SUMMARY
`
`Strategic scoping and focus
`
`The allergic rhinitis market is well established, but remains dynamic with significant changes forecast over the next ten
`years. Patent expiries will have the greatest impact on market size, with different drug classes expected to experience
`differing levels of generic erosion. Datamonitor provides a discussion of the commercial opportunity that remains in this
`market, and analyzes life cycle management strategies that have been utilized by key companies. Trending fon/vard current
`sales and accounting for events that will impact the market, Datamonitor provides a 10—year forecast of key classes and
`brands in the allergic rhinitis market, split by specific indication use estimates.
`
`With changing regulations there is a strong focus on immunotherapy in the allergic rhinitis market, and this niche market is
`explored extensively within this report. A patient based analysis is used to forecast three novel immunotherapy products,
`with patient potential determined on the basis of epidemiology, discussion with key opinion leaders, and analysis of the
`market.
`
`The total allergic rhinitis market is estimated at $5 billion in 2009 in the seven major markets (US, Japan, France, Italy,
`Spain, and the UK). Datamonitor calculates that allergic rhinitis accounted for an average of 37% of the total sales of drugs
`
`in the classes analyzed, which reached $13.5 billion in the same year for all their respective indications.
`
`Datamonitor insight into the allergic rhinitis market
`
`In the course of its research and analysis for Pipeline and Commercial and Insight: Allergic Rhinitis. Datamonitor identified
`the following key conclusions:
`
`.
`
`.
`
`Generic erosion to change the market over the next ten years - Datamonitor estimates allergic rhinitis sales in
`the seven major markets at $5 billion in 2009. This is estimated to drop to $4 billion in 2019, driven by the entrance
`of cheap generics following patent expiries, most notably in the US. Datamonitor has observed a high level of
`generic erosion of oral antihistamines, compared to nasal corticosteroids, and forecast future patent expires based
`on these analogues. This trend is attributed to the device used with nasal corticosteroids, which holds a separate
`patent and can create brand loyalty.
`
`Unmet needs in a small subset of patients are driving development - allergic rhinitis is well treated in the
`majority of patients and unmet needs remain minimal, but subsets of patients with severe uncontrolled disease do
`require alternative treatment options. Datamonitor's analysis of the pipeline for allergic rhinitis revealed that Phase
`III drug candidates consist of immunotherapies, and a nasal antihistamine/nasal corticosteroid combination. Both of
`these classes aim to offer an improved treatment option for patients poorly controlled on symptomatic treatments,
`such that unmet needs appear to be driving development.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640I Published 07/2010
`
`Page 3
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`

`

`Executive Summary
`
`)DATAMONITOR
`
`-
`
`-
`
`Life cycle management strategies involve franchise expansion - in the antihistamine class, a prominent life
`cycle management strategy that has been observed for key brands is the reformulation of molecules and/or
`combinations with decongestants. This strategy helps to maintain sales and strengthen brand recognition following
`patent expiry of the primary molecule. However,
`its success relies heavily on timing of new launches relative to
`generic entry. Merck’s Clarinex (desloratadine) suffered as a result of launching after its predecessor Claritin‘s
`(Ioratadine) patent expired, which was demonstrated by it reaching only a quarter of Claritin’s peak sales in 2009.
`Meda Pharma, on the other hand, has seen successful patient switching from once to twice-daily azelastine having
`launched prior to patent expiry, and is developing an azelastine/fluticasone combination that is expected to further
`strengthen its franchise.
`
`The changing market for immunotherapy will create growth - changing regulations and increasing guidelines
`for immunotherapy are driving development in that class, with the first large—scale development programs seen in
`recent years. Immunotherapy is becoming an evidence based pharmaceutical class, having previously been given
`on a named patient basis with little regulation. Immunotherapy is expected to remain a niche market with cost being
`the greatest constraint, but
`innovation is expected to create significant growth. Two sublingual grass tablets,
`Grazax (ALK-Abellé) and Oralair (Stallergenes) are forecast to have sales of $264m in the US and five major EU
`markets by 2019.
`
`The basis for these conclusions, along with supporting data is provided in the accompanying PowerPoint presentation.
`Forecasts for the seven major markets are provided in the accompanying Excel file of this document.
`
`NB. This report is produced in three parts:
`
`- Word document: contains key conclusions and a summary of the current market and future opportunities and
`threats, outlines the assumptions and events utilized in forecasting the market assesses strategic case studies to
`provide insight into potential market strategies;
`
`-
`
`-
`
`Excel document: contains forecasts on a country—by—country basis for the seven major markets. Volume and value
`forecasts are presented in this file for each of the following levels: country/region, class, molecule and product;
`
`PowerPoint executive presentation: shares Datamonitor’s key insight into the market with supporting data and
`recommendations.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHCZS40I Published 07/2010
`
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`

`

`Executive Summary
`
`) DATA M 0 N ITO R
`
`Related reports
`
`Datamonitor (2009) Pipeline Insight: Asthma 6. COPD — Simplified treatments to split the market, December 2009,
`DMH02569
`
`Datamonitor (2009) Commercial Insight: Asthma 8. COPD— On the verge of generic entry, June 2009, DMH02520
`
`Upcoming related reports
`
`Datamonitor (2010) Forecast Insight: Asthma & COPD, September 2010, DMH02658
`
`Datamonitor (2010) Stakeholder Insight: COPD in Emerging Markets, November 2010, DMHC2633
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Dalamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640l Published 07/2010
`
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`

`

`Table of Contents
`
`) DATA M 0 N ITO R
`
`TABLE OF CONTENTS
`
`OVERVIEW
`
`Catalyst
`
`Summary
`About Datamonitor healthcare
`
`About the immunology & Inflammation pharmaceutical analysis team
`
`EXECUTIVE SUMMARY
`
`Strategic scoping and focus
`
`Datamonltor insight into the allergic rhinitis market
`
`1. PATIENT AND MARKET OVERVIEW
`
`Key findings
`
`Market definition forthis report
`
`Patient potential
`
`Market overview
`
`Opportunities and threats
`
`Seven major market opportunities and threats
`
`US: opportunities and threats
`
`Japan: opportunities and threats
`
`EU: opportunities and threats
`
`Unmet needs
`
`Clinical trial design in allergic rhinitis
`
`Key companies involved in the allergic rhinitis market
`
`2. ORAL ANTIHISTAMINE FRANCHISES
`
`Key findings
`
`Overview of oral antihistamines
`
`Oral antihistamine market size
`
`Allegra/Allegra-D franchise (fexofenadine, Sanofi-A ventis)
`
`Zyrtec/Zyrtec—D/Xyzal franchise (levocetirizine, UCB/Sepracor/Sanofi—A ventis)
`
`Claritin/Clarinex/Clarinex-D franchise (loratadine/desloratadine; Merck)
`
`Late-stage development compounds recently discontinued
`
`3. NASAL CORTICOSTEROIDS
`
`Key findings
`
`1
`
`1
`
`1
`2
`
`2
`
`3
`
`3
`
`3
`
`9
`
`9
`
`10
`
`15
`
`27
`
`30
`
`31
`
`36
`
`43
`
`46
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`49
`
`53
`
`58
`
`62
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`62
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`62
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`64
`
`66
`
`75
`
`85
`
`94
`
`95
`
`95
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`Pipeline and Commercial Insight: Allergic Rhinitis
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`
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`

`

`Table of Contents
`
`)DATAMONITOR
`
`Overview for nasal corticosteroids
`
`Nasal corticosteroid market size
`
`Nasonex (mometasone; Merck)
`
`Feronase/Flonase/Veramyst franchise (fluticasone) GlaxoSmithK/ine
`
`Rhinocort (budesonide; AstraZeneca)
`
`Omnair/Omnaris (ciclesonide; Nycomed/Sepracor)
`
`4. NASAL ANTIHISTAMINES
`
`Key findings
`
`Overview for nasal antihistamines
`
`Nasal antihistamine market size
`
`Astelin/Astepro (azelastine); Meda Pharma
`
`Patanase (olopatadine; Alcon)
`
`5. ANTILEUKOTRIENES
`
`Key findings
`Overview of anti/eukotrienes
`
`Antileukotriene market size
`
`Singulair (montelukast; Merck and Kyorin Pharmaceuticals)
`
`Onon (pranlukast; Ono Pharmaceuticals)
`
`Late-stage development compounds recently discontinued
`
`6. IMMUNOTHERAPY
`
`Key findings
`
`Overview of immunotherapy
`
`Developments in immunotherapy for allergic rhinitis
`
`Methodology and comparative forecasts
`
`Sensitivity analysis
`
`Grazax (ALK-Abellé)
`
`Sta/air Program (Stallergenes)
`
`Pollinex Quattro (Allergy Therapeutics)
`
`Fornix’s sells allergy division to ALK—Abello
`
`Allergopharma moving into sublingual immunotherapy
`
`Roxall and Dr. Beckman collaboration
`
`Greer developing sublingual immunotherapy
`
`95
`
`97
`
`99
`
`104
`
`112
`
`118
`
`126
`
`126
`
`126
`
`127
`
`129
`
`137
`
`142
`
`142
`142
`
`142
`
`145
`
`151
`
`154
`
`156
`
`156
`
`157
`
`159
`
`167
`
`170
`
`171
`
`183
`
`196
`
`203
`
`203
`
`204
`
`204
`
`Pipeline and Commercial Insight: Allergic Rhinitis
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`

`Table of Contents
`
`7. PIPELINE DYNAMICS
`
`Key findings
`
`Pipeline overview
`
`Azelastine/Fluticasone (MP2902; Meda/Cipla)
`
`CDX-313 (azelastine/budesonide; CyDex)
`
`8. CASE STUDY
`
`Introduction
`
`Nasal con'icosteroids
`
`Antihistamines
`
`BIBLIOGRAPHY
`
`Journal papers
`
`Websites
`
`Datamonitor reponfs
`
`APPENDIX A - MARKET ASSUMPTIONS
`
`Forecasting assumptions
`
`Data definitions, limitations and assumptions
`
`Derivation of sales forecasts and pricing trends
`
`APPENDIX B - ALLERGIES PREVALENCE SOURCES
`
`Sources
`
`APPENDIX C
`
`Contributing experts
`
`Conferences attended
`
`Repon methodology
`
`About Datamonitor
`
`Datamonitor consulting
`
`) DATA M 0 N ITO R
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`205
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`205
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`205
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`209
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`215
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`217
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`217
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`224
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`231
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`231
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`237
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`245
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`246
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`246
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`248
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`248
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`250
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`250
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`251
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`251
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`251
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`251
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`251
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`253
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`Pipeline and Commercial Insight: Allergic Rhinitis
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`

`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`1. PATIENT AND MARKET OVERVIEW
`
`Key findings
`
`.
`
`-
`
`Datamonitor estimates that there are approximately 181m people living with allergic rhinitis in the seven major
`markets (US, Japan, France, Germany, Italy, Spain, and the UK). This is based on self-reported questionnaires,
`such that this is a maximum estimate including both diagnosed and undiagnosed disease. These patients can be
`segmented by severity, with approximately 81% having either moderate/severe intermittent or moderate/severe
`persistent allergic rhinitis.
`
`Key drug classes used to treat allergic rhinitis are estimated to have been worth a total of $13.5 billion in 2009 in
`the seven major markets. Using IMS Prescribing Insights data to split individual products by indication, Datamonitor
`estimates that 37% of this, roughly $5 billion, was attributed to allergic rhinitis specifically.
`
`- While the volume of drug sales is seen to be increasing slightly by an estimated CAGR of 0.5% from 2009—2019,
`value is decreasing, owing to increased generic erosion. This is expected to continue over the next ten years, with
`the expiries of key patents.
`
`-
`
`Opportunities and threats in the allergic rhinitis market have been identified across the seven major markets. A key
`opportunity is the shift to over-the-counter status. The potential for this is greatest in the US and EU, although new
`regulations are increasing opportunity in Japan as well. The greatest threat to the market is generic erosion. While
`
`this will have the greatest impact in the US, increasing focus on cost containment in the EU and Japan is expected
`to impact generic uptake.
`
`. While generally considered well treated, some unmet needs remain in allergic rhinitis. A subset of patients,
`estimated to represent 15-20% of the patient population, continue to suffer symptoms despite the use of
`symptomatic treatments. Furthermore, compliance remains a key issue in treating the disease.
`
`.
`
`Clinical trial design in allergic rhinitis has seen a shift in recent years. While traditional symptom scores continue to
`be widely used as primary endpoints, a new approach, which adjusts symptom scores for the use of rescue
`medication,
`is gaining popularity. This approach has been most widely used in the recent development of
`immunotherapy, and was first advocated in the European Medicine Agency‘s (EMA) guidelines on the clinical
`development of products for specific immunotherapy for
`the treatment of allergic diseases (EMA, 2008;
`http://wwwemaeurogaeu).
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
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`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`Market definition for this report
`
`The market analysis and forecasts in this report uses both IMS Health data and patient-based forecasts to size the market.
`The following Anatomical Therapeutic Classification (ATC) drug classes are used to define the current allergic rhinitis
`market:
`
`-
`
`-
`
`-
`
`.
`
`.
`
`-
`
`.
`
`-
`
`.
`
`.
`
`R1A1: nasal corticosteroids;
`
`R1A6: nasal anti-allergic agents;
`
`R1A7: nasal decongestants;
`
`R1 B0: systemic nasal preparations;
`
`R6A0: systemic antihistamines;
`
`R3J2:antileukotrienes;
`
`V1A0: allergens.
`
`For the purposes of this report, Datamonitor has split sales by indication using IMS Prescribing Insights data, and we have
`defined allergic rhinitis as comprising the following International Classification of Diseases, version 10 (lCD-10) diagnoses:
`
`J301: allergic rhinitis — pollen;
`
`J302: other seasonal allergic rhinitis;
`
`J303: other allergic rhinitis;
`
`J304: allergic rhinitis unspecified;
`
`J310; chronic allergic rhinitis,
`
`Throughout this report; the term ‘seven major markets‘ (or 7MM) refers to the major pharmaceutical markets; comprising
`
`the US; Japan; France, Germany; Italy, Spain and the UK.
`
`For a detailed methodology regarding market definition. please see the section entitled Data definitions. limitations and
`assumptions in Appendix A.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHCZ640I Published 07/2010
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`

`Patient and Market Overview
`
`)DATAMONITOR
`
`Sales split by indication
`
`For this report Datamonitor analyzed sales of key classes and brands in allergic rhinitis by considering total sales, and our
`estimate of sales by indication. To do so, data from MIDAS Prescribing Insights was utilized, applying the percentage of
`sales prescribed for each indication. MIDAS Prescribing Insights data is collected from physician diary information. Differing
`numbers of specialists are sampled in each country, which can impact the validity of the data. Table 1 shows physician
`
`coverage by country of relevant specialties. The panel size represents the number of physicians surveyed, while country
`total gives the total number of physicians of each specialty within each country.
`It is clear that for some countries, such as
`the US and Germany, coverage is greater than, for instance, Spain and the UK. As a result, data is considered more robust
`for these countries, and at times Datamonitor has, for example, used Germany as a proxy for other European countries.
`Total brand sales are shown as well as sales split by indication in the excel deliverable accompanying this report, in order
`to put all sales in context.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640l Published 07/2010
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`

`Patient and Market Overview
`
`)DATAMONITOR
`
`
`
`
`
`MIDAS PrescribinTable 1: ' hts Pt: sician Covera- e, 2010
`
`
`
`Specialties Covered
`
`USA
`
`Allergy
`General Practice
`Pulmonary Diseases
`
`Japan
`Internal Medicine &
`Gastroenterology
`
`France
`General Practitioners
`Pulmology
`
`Germany
`General Practitioner + Internists
`ENT-doctors
`
`Pneumologists
`
`Italy
`General Medicrne
`Pneumologists
`
`Spain
`General Medicine
`Respiratory System
`
`UK
`General Practitioner
`
`Panel Size
`
`Country total
`
`“/n represented
`
`150
`108
`108
`
`299
`
`400
`20
`
`900
`150
`
`60
`
`667
`50
`
`160
`30
`
`500
`
`3315
`5632
`4741
`
`52,438
`
`60,392
`1141
`
`63,111
`4050
`
`775
`
`46,894
`3,213
`
`24,389
`2039
`
`42,086
`
`5%
`2%
`2%
`
`1%
`
`1%
`2%
`
`1%
`4%
`
`7.7%
`
`1%
`1.6%
`
`1%
`1%
`
`1%
`
`ource: Prescribing Insights, IMS Health, March 2010, Copyright ©, reprinted with
`ermission.
`
`DATAMONITOR
`
`
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640I Published 07/2010
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`Page 12
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`

`

`Patient and Market Overview
`
`)DATAMONITOR
`
`Using Prescribing Insights data, Datamonitor split sales by indication. The proportion of sales attributable to different
`
`indications varies by drug class. For oral antihistamines and nasal corticosteroids, allergic rhinitis makes up roughly half of
`all sales, while for antileukotrienes, allergic rhinitis accounts for just 20% of sales, with the majority attributable to asthma.
`The indication split for these classes is shown in Figure 1.
`
`
`
`Fi ure 1:
`
`K9 classes in aller ic rhinitis slit h indication, 2009
`
`
`
`Oral antihistamines
`All Others
`Asthma
`4%
`5%
`
`Nasal corticosteroids
`All Others
`Asthma
`3%
`5%
`
`Antileukotrienes
`All Diners
`2%
`
`Al Ina-mic Rhinitis
`
`other alergiealFJdT
`35%
`
`Nierg'i: Rhinitis
`
`55%
`
`one» Hugh-SPENT
`
`Allergic Rhinitis
`20%
`
`war dlanj aa'ENT
`
`D A TA M o N I T o R
`45%
`
`
`Source: MIDAS Sales Data and Prescribing Insight, IMS Health, March 2010, Copyright ©,
`
`reprinted with permission
`
`
`Sales forecasts of key brands are provided at both the total brand level, and by indication,
`accompanies this report.
`
`in the excel deliverable that
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640I Published 07/2010
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`

`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`Over- the-counter market impact
`
`Several companies in the allergic rhinitis market have shifted their products to over—the—counter (OTC) status, most
`commonly in the oral antihistamine class. This can help to reduce the loss of patients to generics, as OTC products are
`generally cheaper than prescription brands, and direct-to-consumer advertising is extensively used to create brand
`recognition and loyalty.
`
`Datamonitor’s forecast is based on IMS MIDAS sales data, which primarily represents prescription sales, with minimal OTC
`sales captured.
`In forecasting generic erosion, Datamonitor assumes that products will remain only on the prescription
`market, such that the potential impact of an OTC switch is not represented. In the case that a product does move OTC, this
`would overestimate the uptake of generics.
`
`Figure 2 depicts the way that patent expiries and a shift to OTC can impact branded prescription sales. Vlfith a patent
`expiry, branded prescription sales are split with generic prescription sales. In the case that a brand moves OTC, branded
`prescription sales are split between branded OTC sales, and when the product is off—patent, generic OTC sales.
`
`
`
`The imoact of atent ex~ ir'res and over~the»counter shifts on branded corescri '
`
`Branded
`
`prescription
`sales
`
`Branded prescription
`ewes
`
`Generic prescription
`sdes
`
`counter sales Source: Datamonitor
`
`Branded. over the
`c punter sales
`
`Generic over the
`
`D A T A M o N I T o R
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHCZS40/ Published 07/2010
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`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`Patient potential
`
`Disease definition
`
`Allergic rhinitis is a disease characterized by symptoms such as sneezing, watery nasal discharge, nasal obstruction and
`itching, associated with inflammation. The most likely cause of allergic rhinitis is underdevelopment of the immune system
`in childhood, while the most significant risk factors include a personal and family history of asthma and other allergies, such
`as eczema and hives. Heredity is a major factor in atopy which predisposes an individual to allergic disease.
`
`Initial contact with an allergen sensitizes the immune system and leads to the production of immunoglobulin E (IgE), which
`can then bind to the surface of mast cells. On re-exposure, allergens bind and cross-link IgE molecules on the surface of
`mast cells beneath the mucosal surfaces of the throat and nose (Walls et at, 2005). This interaction between the antigen
`
`and IgE molecule causes the subsequent release of mediators, including histamine. which results in the symptoms of
`allergic rhinitis in the nose, throat and eyes within minutes of allergen exposure (early-phase response) (Naclerio, 1999).
`This is followed several hours later by the late-phase response,
`involving the infiltration of inflammatory cells and the
`release of mediators into the nasal mucosa. The symptoms are essentially the same as in the early—phase response, but
`congestion predominates.
`
`Minimal persistent inflammation is an important concept in the etiology of allergic rhinitis. Accumulating evidence suggests
`that allergic rhinitis is a chronic inflammatory disease instead of a disease of acute symptoms (Storms, 2003). In patients
`with persistent allergic rhinitis, allergen exposure varies throughout the year and there are periods where contact is minimal
`
`(2000) shows that subjects with seasonal allergic rhinitis had a significant
`(ARIA, 2008). A study performed by Ricca et al.
`inflammatory reaction throughout the pollen season, even during periods with a low pollen count, but that symptoms were
`low or absent (Storms, 2003).
`
`Patient segmentation
`
`Allergic rhinitis has traditionally been categorized as either ‘seasonal', where pollen or moulds are the usual triggers, or
`'perennial‘,
`in which case house dust mites or pet dander allergens are typically responsible. Sometimes the category
`‘occupational allergic rhinitis‘ is used, although this is not standard and is difficult to differentiate from other subsets of
`rhinitis. This set of subdivisions was regarded as unsatisfactory, and a new system of classification for allergic rhinitis was
`
`proposed by Allergic Rhinitis and its impact on Asthma (ARIA) guidelines in 2001, with an update in 2008, which:
`
`.
`
`.
`
`-
`
`uses symptom-based and quality of life parameters;
`
`is based on duration, and is subdivided into ‘intermittent’ and ‘persistent’ disease;
`
`is based on severity, and has subsets for ‘mild‘ and ‘moderate/severe’ depending on symptoms and quality of life.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
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`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`
`
`Fi ure 3:
`
`Allen in rhinitis and its im act on asthma ARIA classification. 2008
`
`Intermitlent symptom:
`<11 days per-week OR for <4
`cunS'ecutive-weeks
`
`Persistent symptoms
`i=4 clays pBrwa-ek OR for >4
`consecutive weeks
`
`
`
`
`Source: Datamonitor adapted from ARIA, 2008
`
`D A T A M O N I T O R
`
`”i tend to use the ARIA classification, mild, moderate, severe, and intermittent versus persistent.”
`
`UK key opinion leader
`
`(2006) studied the effect of allergic rhinitis using the new classification as proposed by ARIA. Out of a total
`Bousquet et al.
`of 3,052 patients consulting general practitioners for this disease, mild intermittent rhinitis was diagnosed in 11% of the
`patients, moderate/severe intermittent rhinitis in 35%, mild persistent rhinitis in 8%, and moderate/severe persistent rhinitis
`in 46% of the patients.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
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`

`Patient and Market Overview
`
`)DATAMONITOR
`
` Distribution of severit: of dia nosed aller- it: rhinitis patients
`Mild intermittent
`
`
`
`Moderatetsevere
`
`persistent
`
`Moderater’severe
`intermittent
`
`Mild persistent
`Source: Bousquet et al ., 2006 D A T A M o N I T 0 R
`
`
`
`Based on these results, over 80% of patients had a moderate/severe form of allergic rhinitis, however, it must be noted that
`this study over—represents more severe patients, as patients with milder symptoms are less motivated to visit their doctor
`and may prefer to self-medicate. This over-representation of more severe cases was confirmed in discussions with key
`opinion leaders, and distinguishes allergic rhinitis from diseases such as asthma,
`in which patients with more severe
`symptoms are the minority.
`
`r‘l would say with the bias of my practice, it is not quite like asthma where you have a lesser percentage [of
`moderate to severe patients], I think you might have 60% falling into the moderate to severe category, in the
`
`ARIA guidelines.”
`
`US key opinion leader
`
`Seven major markets
`
`Figure 5 shows the allergic rhinitis populations in the seven major markets (US, Japan, France, Germany, Italy, Spain, and
`the UK) for 2010. Datamonitor estimates that the allergic rhinitis population totals 181 million across these countries. This is
`based on self-reported questionnaires, such that the sum includes both diagnosed and undiagnosed disease. The largest
`population (80 million) is seen in the US, and the smallest (6 million),
`in Spain. The differences between countries are
`
`largely attributable to total p0pulation sizes, with an impact from variations in local allergens as well. Furthermore, within
`each country, the prevalence rates can change as pollen seasons differ.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
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`

`Patient and Market Overview
`
`) DATA M 0 N ITO R
`
`“In our region we demonstrated that there was an increase of pollen [over 27 years] and there was also an
`increase in the number of days [in a pollen season].“
`
`EU key opinion leader
`
`“There is the perspective that in 2020, one out of every two pediatric patients will have allergic rhinitis.
`
`EU key opinion leader
`
`
`Fi ure 5: