`
`
`
`
`
`
`»DATAMONITOR
`
`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. With significant change seenin clinical development, immunotherapy is attracting increasing attention,
`and is the center of innovation in allergic rhinitis.
`
`Summary
`
`«
`
`e
`
`e
`
`e
`
`Datamonitor estimates that the allergic rhinitis market reached $5 billion in the seven major markets in 2009, and
`forecasts thatit 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. With numerous
`products in the pipeline the immunotherapy market is set to experience significant growth, and Datamonitor
`forecasts two key late-stage sublingual immunotherapytablets;
`
`Datamonitor identified two nasal antihistamine/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
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`MEDA_APTX03502401
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`Argentum Pharmaceuticals LLC v. Cipla Ltd.
`IPR2017-00807
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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:
`
`Bormmadata (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 leaderintelligence and best-in-class case studies, leading to actionable recommendations;
`
`e
`
`.
`
`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
`cdavies@datamonitor.com.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640/ Published 07/2010
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`

`

`Executive Summary
`
`EXECUTIVE SUMMARY
`
`Strategic scoping and focus
`
`DATAMONITOR
`
`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 remainsin this
`market, and analyzeslife cycle managementstrategies that have been utilized by key companies. Trending forward current
`sales and accounting for events that will impact the market, Datamonitor provides a 10-year forecast of key classes and
`brandsin the allergic rhinitis market, split by specific indication use estimates.
`
`With changing regulations there is a strong focus on immunotherapyin the allergic rhinitis market, and this niche marketis
`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 totalallergic 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 thetotal sales of drugs
`
`in the classes analyzed, which reached $13.5 billion in the same yearforall their respective indications.
`
`Datamonitor insight into the allergic rhinitis market
`
`In the course ofits 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 estimatesallergic 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 altemative treatment options. Datamonitor's analysis of the pipeline for allergic rhinitis revealed that Phase
`lll 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 appearto be driving development.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640/ Published 07/2010
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`Page 3
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`

`

`Executive Summary
`
`DATAMONITOR
`
`e
`
`*
`
`Life cycle management strategies involve franchise expansion - in the antihistamine class, a prominentlife
`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 launchesrelative to
`generic entry. Merck’s Clarinex (desloratadine) suffered as a result of launching after its predecessor Claritin’s
`(loratadine) patent expired, which was demonstrated by it reaching only a quarterof 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
`strengthenits franchise.
`
`The changing market for immunotherapy will create growth - changing regulations and increasing guidelines
`for immunotherapy are driving developmentin 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-Abell6) and Oralair (Stallergénes) 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 Excelfile of this document.
`
`N.B. This report is producedin 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;
`
`°
`
`e
`
`Excel document: contains forecasts on a country-by-country basis for the seven major markets. Volume and value
`forecasts are presentedin 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
`
`DMHC2640/ Published 07/2010
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`

`

`Executive Summary
`
`» DATAMONITOR
`
`Related reports
`
`Datamonitor (2009) Pipeline Insight: Asthma & COPD — Simplified treatments to split the market, December 2009,
`DMHC2569
`
`Datamonitor (2009) Commercial Insight: Asthma & COPD—Onthe verge of generic entry, June 2009, DMHC2520
`
`Upcomingrelated reports
`
`Datamonitor (2010) Forecast insight: Asthma & COPD, September 2010, DMHC2658
`
`Datamonitor (2010) Stakeholder insight: COPD in Emerging Markets, November 2010, DMHC2633
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640/ Published 07/2010
`
`Page 5
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`

`

`Table of Contents
`
`» DATA M 0 N ITO R
`
`_o6
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`©YB©8FRBS
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`TABLE OF CONTENTS
`
`OVERVIEW
`
`Catalyst
`
`Summary
`About Datamonitor healthcare
`
`About the immunology & Inflammation pharmaceutical analysis team
`
`EXECUTIVE SUMMARY
`
`Strategic scoping and focus
`
`Datamonitor insight into the allergic rhinitis market
`
`1. PATIENT AND MARKET OVERVIEW
`
`Keyfindings
`
`Marketdefinition for this report
`
`Patient potential
`
`Market overview
`
`Opportunities and threats
`
`Seven major market opportunities and threais
`
`US: opportunities and threats
`
`Japan: opportunities and threats
`
`EU: opportunities and threats
`
`Unmet needs
`
`Clinical trial design in allergic rhinitis
`
`Key companiesinvolvedin the allergic rhinitis market
`
`2. ORAL ANTIHISTAMINE FRANCHISES
`
`Keyfindings
`
`Overview oforal antihistamines
`
`Oral antihistamine marketsize
`
`Allegra/Allegra-D franchise (fexofenadine, Sanofi-Aventis)
`
`Zyrtec/Zyrtec-D/Xyzal franchise (levocetirizine, UCB/Sepracor/Sanofi-Aventis)
`
`Claritin/Clarinex/Clarinex-D franchise (loratadine/desioratadine; Merck)
`
`Late-stage development compounds recently discontinued
`
`3. NASAL CORTICOSTEROIDS
`
`Keyfindings
`
`Pipeline and CommercialInsight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
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`Table of Contents
`
`Overview for nasal corticosteroids
`
`Nasalcorticosteroid market size
`
`Nasonex (mometasone; Merck)
`
`Flixonase/Flonase/Veramystfranchise (fluticasone) GlaxoSmithKline
`
`Rhinocort (budesonide; AstraZeneca)
`
`Omnair/Omnaris (ciclesonide; Nycomed/Sepracor)
`
`4. NASAL ANTIHISTAMINES
`
`Keyfindings
`
`Overview for nasal antihistamines
`
`Nasal antihistamine marketsize
`
`Astelin/Astepro (azelastine); Meda Pharma
`
`Patanase (olopatadine; Alcon)
`
`5. ANTILEUKOTRIENES
`
`Keyfindings
`Overview of antileukotrienes
`
`Antileukotriene marketsize
`
`Singulair (montelukast; Merck and Kyorin Pharmaceuticals)
`
`Onon (pranlukast; Ono Pharmaceuticals)
`
`Late-stage development compoundsrecently discontinued
`
`6. IMMUNOTHERAPY
`
`Keyfindings
`
`Overview of immunotherapy
`
`Developments in immunotherapyfor allergic rhinitis
`
`Methodology and comparative forecasis
`
`Sensitivity analysis
`
`Grazax (ALK-Abelid)
`
`Stalair Program (Stallergénes)
`
`Pollinex Quattro (Allergy Therapeutics)
`
`Fornix’s sells allergy division to ALK-Abell6
`
`Allergopharma moving into sublingual immunotherapy
`
`Roxall and Dr. Beckman collaboration
`
`Greer developing sublingual immunotherapy
`
`DATAMONITOR
`
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`Pipeline and Commercial Insight: Allergic Rhinitis
`
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`Table of Contents
`
`7. PIPELINE DYNAMICS
`
`Keyfindings
`
`Pipeline overview
`
`Azelastine/Fluticasone (MP2902; Meda/Cipla)
`
`CDX-313 (azelastine/budesonide; CyDex)
`
`8. CASE STUDY
`
`Introduction
`
`Nasalcorticosteroids
`
`Antihistamines
`
`BIBLIOGRAPHY
`
`Journal papers
`
`Websites
`
`Datamonitor reports
`
`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
`
`Conferencesattended
`
`Report methodology
`
`About Datamonitor
`
`Datamonitor consulting
`
`» DATA M 0 N ITO R
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`Pipeline and CommercialInsight: Allergic Rhinitis
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`

`Patient and Market Overview
`
`» DATA M 0 N ITO R
`
`1. PATIENT AND MARKET OVERVIEW
`
`Keyfindings
`
`°
`
`°
`
`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
`persistentallergicrhinitis.
`
`Key drug classes usedto 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 $5billion, was attributed to allergic rhinitis specifically.
`
`e 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.
`
`e
`
`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 containmentin the EU and Japan is expected
`to impact generic uptake.
`
`e 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 keyissuein 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:/Awww.ema.europa.eu).
`
`Pipeline and CommercialInsight: 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
`
`Marketdefinition 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: nasalanti-allergic agents;
`
`*—R1A7: nasal decongestants;
`
`°
`
`°
`
`«
`
`e
`
`*
`
`°
`
`R1B0: systemic nasal preparations;
`
`R6A0: systemic antihistamines;
`
` R3J2: antileukotrienes;
`
` V1A0: allergens.
`
`For the purposesofthis 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 (ICD-10) diagnoses:
`
` J301: allergic rhinitis — pollen;
`
`J302: other seasonal allergic rhinitis;
`
`e—_J303: otherallergic rhinitis;
`
`°
`
`.
`
`J304:allergic rhinitis unspecified;
`
`J310; chronic allergic rhinitis.
`
`Throughoutthis 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 andis not to be photocopied
`
`DMHC2640/ 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 brandsin 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 numberof physicians of each specialty within each couniry.
`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 putall sales in context.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product andis not to be photocopied
`
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`Patient and Market Overview
`
`DATAMONITOR
`
`
`Table 1:
`MIDAS Prescribing
`hts Physician Coverage, 2010
`
`DATAMONITOR
`
`
`
`Specialties Covered
`
`USA
`
`Allergy
`General Practice
`Pulmonary Diseases
`
`Japan
`Internal Medicine &
`Gastroenterology
`
`France
`General Practitioners
`Pulmology
`
`Germany
`GeneralPractitioner + Internists
`ENT-doctors
`
`Pneumologists
`
`Italy
`General Medicine
`Pneumologists
`
`Spain
`General Medicine
`Respiratory System
`
`UK
`General Practitioner
`
`Panel Size
`
`Country total
`
`150
`108
`108
`
`299
`
`400
`20
`
`900
`150
`60
`
`667
`50
`
`160
`30
`
`$00
`
`3315
`$632
`4741
`
`52,438
`
`60,392
`1141
`
`63,111
`4050
`775
`
`46,894
`3,213
`
`24,389
`2039
`
`42,086
`
`ource: Prescribing Insights, IMS Health, March 2010, Copyright ©, reprinted with
`ermission.
`
`% represented
`
`5%
`2%
`2%
`
`1%
`
`1%
`2%
`
`1%
`4%
`7.7%
`
`1%
`1.6%
`
`1%
`1%
`
`1%
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640/ Published 07/2010
`
`Page 12
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`HIGHLY CONFIDENTIAL -
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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 shownin Figure 1.
`
`
`
`Key classes in allergic rhinitis split by
`
`indication, 2009
`
`Oral antihistamines
`All Others
`Asthma
`4%
`5%
`
`Nasalcorticosteroids
`All Others
`Asthma
`6%
`
`Antileukotrienes
`All Others
`2%
`
`Allergic Rhinitis
`Cri
`
`PeeaePeeta
`ey
`
`ree isa
`Ci
`
`Allergic Rhinits
`Et
`
`erea
`a)
`
`eneeelLh
`
`DATAMONITOR
`39,
`\
`
`
`
`
`
`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 byindication, in the excel deliverable that
`accompaniesthis report.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product andis not to be photocopied
`
`DMHC2640/ Published 07/2010
`
`Page 13
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`

`

`Patient and Market Overview
`
`DATAMONITOR
`
`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 MIDASsales 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. With 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 whenthe productis off-patent, generic OTC sales.
`
`
`
`Figure 2:
`
`The impact of patent expiries and over-the-counter shifts on branded prescription sales, 2010
`
`counter sales Source: Datamonitor
`
`arerevelcte
`prescription
`sot
`
`Events
`
`Branded prescription
`TE
`
`Generic prescription
`FT
`
`Brandedover the
`counter sales
`
`Generic over the
`
`DATAMONITOR
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product andis not to be photocopied
`
`DMHC2640/ Published 07/2010
`
`Page 14
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`

`

`Patient and Market Overview
`
`» DATA M 0 N ITO R
`
`Patient potential
`
`Diseasedefinition
`
`Allergic rhinitis is a disease characterized by symptoms such as sneezing, watery nasal discharge, nasal obstruction and
`itching, associated with inflammation. The mostlikely cause of allergic rhinitis is underdevelopmentof the immune system
`in childhood, while the mostsignificantrisk factors include a personal and family history of asthma and otherallergies, such
`as eczema and hives. Heredity is a major factor in atopy which predisposesan individualto 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 ef a/., 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 seasonalallergic rhinitis had a significant
`(ARIA, 2008). A study performed by Ricca et af.
`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 danderallergens 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
`
`proposedbyAllergic Rhinitis and its impact on Asthma (ARIA) guidelines in 2001, with an update in 2008, which:
`
`*
`
`uses symptom-based and quality oflife parameters,
`
`¢—is based on duration, and is subdivided into ‘intermittent’ and ‘persistent’ disease;
`
`e
`
`is based on severity, and has subsets for ‘mild’ and ‘moderate/severe’ depending on symptoms and quality oflife.
`
`Pipeline and CommercialInsight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product andis not to be photocopied
`
`DMHC2640/ Published 07/2010
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`

`

`Patient and Market Overview
`
`DATAMONITOR
`
`
`
`Allergic rhinitis and its impact on asthma (ARIA) classification, 2003
`
`Intermittent symptoms
`<4 days per week OR for <4
`consecutive weeks
`
`Persistent symptoms
`=4 days per week OR for >4
`consecutive weeks
`
`Source: Datamonitor adapted from ARIA, 2008
`
`DATAMONITOR
`
`“| 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 ef a/.
`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 persistentrhinitis
`in 46% of the patients.
`
`Pipeline and CommercialInsight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product and is not to be photocopied
`
`DMHC2640/ Published 07/2010
`
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`

`

`Patient and Market Overview
`
`DATAMONITOR
`
` Distribution of severity of diagnosed allergic rhinitis patients
`
`Moderate/severe
`
`persistent
`
`Moderate/sey ere
`intermittent
`
`Mild intermittent
`
`Mild persistent
`Source: Bousquetet a/ ., 2006 DATAMONITOR
`
`
`
`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
`symptomsare the minority.
`
`“I 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], / 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 showstheallergic 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 population sizes, with an impact from variations in local allergens as well. Furthermore, within
`each country, the prevalence rates can change as pollen seasonsdiffer.
`
`Pipeline and Commercial Insight: Allergic Rhinitis
`
`© Datamonitor. This report is a licensed product andis not to be photocopied
`
`DMHC2640/ Published 07/2010
`
`Page 17
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`HIGHLY CONFIDENTIAL -
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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 numberofdays [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 keyopinion leader
`
`
`
`Allergic rhinitis prevalent population in the seven major markets, 2010
`
`Figure 5:
`
`Total allergic rhinitis population: 181 million
`
`;
`
`B Adult allergic rhinitis population
`@ Pediatric allergic rhinitis population
`
`
`
`90
`60
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`"
`
`DATAMONITOR
`
`
`i Z
`
`France
`
`" Germany
`
`Japan
`
`aHm
`
`Italy
`
`Spain
`
`Source: See Tabl