Gastrointestinal Therapeutics Sample · Gastrointestinal Therapeutics in Major Developed Markets to 2019 New Drug Approvals and Promising Pipeline to Counter Declines from Patent

Gastrointestinal Therapeutics in Major Developed Markets to 2019 New Drug Approvals and Promising Pipeline to Counter Declines from Patent Expiries

GBI Research Report Guidance

© GBI Research. This is a licensed product and is not to be photocopied GBIHC318MR / Published JAN 2014 Page 2

GBI Research Report Guidance

The second chapter of this report provides an introduction to GI therapeutic indications of IBS, UC and CD, including epidemiology, symptoms, etiology, pathophysiology, diagnosis, disease classification and determination of disease severity, and treatment.

The third chapter provides an overview of the product profiles for six key marketed products for IBS, UC, and CD.

The fourth chapter analyses the IBS, UC, and CD pipelines, detailing, among other parameters, drug distribution by phase, molecule type and mechanism of action. The chapter also profiles three promising drug candidates in the pipeline.

The fifth chapter provides a market forecast to 2019 for major developed markets (the US, Canada, the UK, France, Germany, Italy, Spain, and Japan), which is displayed in chapter five, and includes prevalence population, Annual Cost of Therapy (ACoT) and a market size forecast, along with drivers and barriers for the GI market.

Chapter six provides a strategic consolidation analysis, including major co-development and licensing deals.

© GBI Research. This is a licensed product and is not to be photocopied GBIHC318MR / Published JAN 2014

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Executive Summary

Executive Summary

Gastrointestinal Therapeutics Market in Major Developed Markets to Decline by XX% to $XX Billion in 2019

The Gastrointestinal (GI) therapeutics market for Irritable Bowel Syndrome (IBS), Ulcerative Colitis (UC), and Crohn’s Disease (CD) in the major markets of the US, Canada, the UK, France, Germany, Italy, Spain, and Japan was worth an estimated $XX billion in 2012, a total that is expected to decline at a Compound Annual Growth Rate (CAGR) of XX% during the forecast period to $XX billion in 2019.

The GI therapeutics market is forecast to register different CAGR rates across the eight major geographical markets, with Japan expected to register the fastest growth rate at a CAGR of XX%, followed by the US with XX%. Other major markets are expected to decline during the forecast period, Canada at a negative rate of XX%, the UK at a negative rate of XX%, France at a negative rate of XX%, Germany at a negative rate of XX%, Italy at a negative rate of XX%, and Spain at a negative rate of XX%. The US is the leader among the major developed markets, with a market value of $XX billion in 2012, equivalent to almost XX% of the total GI major developed market. By 2019, the GI therapeutics market is expected to have declined due to the patent expiry of major drugs during the forecast period.

Gastrointestinal Therapeutics Market, Major Developed Markets, Market Size ($bn), 2012–2019

2012 2019

Rev

enue

($bn

)

US Top five European countries Canada Japan

Source: GBI Research Proprietary Products Database [accessed October 16, 2013]

The GI therapeutics market is forecast to register different CAGR rates across the eight major geographical markets


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Table of Contents

1 Table of Contents

1 Table of Contents ................................................................................................................................. 6 1.1 List of Tables ............................................................................................................................. 9 1.2 List of Figures...........................................................................................................................11

2 Gastrointestinal Therapeutics in Major Developed Markets – Introduction ...........................................12 2.1 Irritable Bowel Syndrome .........................................................................................................12

2.1.1 Classification ....................................................................................................................12 2.1.2 Symptoms ........................................................................................................................12 2.1.3 Etiology ...........................................................................................................................12 2.1.4 Pathophysiology...............................................................................................................13 2.1.5 Diagnosis .........................................................................................................................13 2.1.6 Epidemiology ...................................................................................................................14 2.1.7 Prognosis .........................................................................................................................15 2.1.8 Treatment Options ...........................................................................................................15

2.2 Ulcerative Colitis ......................................................................................................................16 2.2.1 Classification ....................................................................................................................16 2.2.2 Symptoms ........................................................................................................................17 2.2.3 Etiology ...........................................................................................................................17 2.2.4 Pathophysiology...............................................................................................................18 2.2.5 Diagnosis .........................................................................................................................18 2.2.6 Epidemiology ...................................................................................................................19 2.2.7 Prognosis .........................................................................................................................19 2.2.8 Treatment Options ...........................................................................................................20

2.3 Crohn’s Disease .......................................................................................................................21 2.3.1 Classification ....................................................................................................................21 2.3.2 Symptoms ........................................................................................................................22 2.3.3 Etiology ...........................................................................................................................22 2.3.4 Pathophysiology...............................................................................................................23 2.3.5 Diagnosis .........................................................................................................................23 2.3.6 Epidemiology ...................................................................................................................24 2.3.7 Prognosis .........................................................................................................................24 2.3.8 Treatment Options ...........................................................................................................25

3 Gastrointestinal Therapeutics in Major Developed Markets – Marketed Products (Global) ...................26 3.1 Irritable Bowel Syndrome .........................................................................................................26 3.2 Ulcerative Colitis ......................................................................................................................26 3.3 Crohn’s Disease .......................................................................................................................26 3.4 Key Marketed Products ............................................................................................................27

3.4.1 Amitiza ............................................................................................................................27 3.4.2 Humira ............................................................................................................................28 3.4.3 Remicade .........................................................................................................................29 3.4.4 Simponi ...........................................................................................................................30 3.4.5 Cimzia..............................................................................................................................31 3.4.6 Tysabri .............................................................................................................................32

4 Gastrointestinal Therapeutics in Major Developed Markets – Pipeline Analysis ....................................34 4.1 Irritable Bowel Syndrome .........................................................................................................34

4.1.1 Overall Pipeline ................................................................................................................34 4.1.2 Pipeline Analysis by Molecule Type ...................................................................................36 4.1.3 Pipeline Analysis by Mechanism of Action .........................................................................37

4.2 Ulcerative Colitis Pipeline .........................................................................................................39 4.2.1 Overall Pipeline ................................................................................................................39 4.2.2 Pipeline Analysis by Molecule Type ...................................................................................41


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Table of Contents

4.2.3 Pipeline Analysis by Mechanism of Action .........................................................................42 4.3 Crohn’s Disease Pipeline ..........................................................................................................44

4.3.1 Overall Pipeline ................................................................................................................44 4.3.2 Pipeline Analysis by Molecule Type ...................................................................................46 4.3.3 Pipeline Analysis by Mechanism of Action .........................................................................47

4.4 Promising Drug Candidates in the Pipeline ................................................................................49 4.4.1 GSK-1605786 ...................................................................................................................49 4.4.2 MLN0002 .........................................................................................................................49 4.4.3 EMD-61753 ......................................................................................................................49

5 Gastrointestinal Therapeutics in Major Developed Markets – Market Forecast to 2019 ........................50 5.1 Major Developed Markets........................................................................................................50

5.1.1 Treatment Usage Patterns................................................................................................50 5.1.2 Annual Cost of Therapy ....................................................................................................50 5.1.3 Market Size ......................................................................................................................50

5.2 US ...........................................................................................................................................52 5.2.1 Treatment Usage Patterns................................................................................................52 5.2.2 Annual Cost of Therapy ....................................................................................................52 5.2.3 Market Size ......................................................................................................................52

5.3 Europe.....................................................................................................................................54 5.3.1 Treatment Usage Patterns................................................................................................54 5.3.2 Annual Cost of Therapy ....................................................................................................54 5.3.3 Market Size ......................................................................................................................54

5.4 Canada ....................................................................................................................................56 5.4.1 Treatment Usage Patterns................................................................................................56 5.4.2 Annual Cost of Therapy ....................................................................................................56 5.4.3 Market Size ......................................................................................................................56

5.5 Japan .......................................................................................................................................58 5.5.1 Treatment Usage Patterns................................................................................................58 5.5.2 Annual Cost of Therapy ....................................................................................................58 5.5.3 Market Size ......................................................................................................................58

5.6 Drivers and Barriers .................................................................................................................60 5.6.1 Drivers .............................................................................................................................60 5.6.2 Barriers ............................................................................................................................60

6 Gastrointestinal Therapeutics in Major Developed Markets – Deals and Strategic Consolidations (Global)...........................................................................................................................................................62

6.1 Deals Analysis ..........................................................................................................................62 6.2 Major Co-Development Deals...................................................................................................64

6.2.1 AstraZeneca Enters into Co-Development Agreement with Ironwood Pharma for Linaclotide ........................................................................................................................................65

6.2.2 Amgen Enters into Co-development Agreement with AstraZeneca for Five Monoclonal Antibodies........................................................................................................................65

6.2.3 Galapagos and AbbVie Extend GLPG0634 Development Agreement to Include Crohn's Disease ............................................................................................................................65

6.3 Major Licensing Deals ..............................................................................................................66 6.3.1 AstraZeneca Enters into Licensing Agreement with Ardelyx for NHE3 Inhibitor Program .....67 6.3.2 Sanofi-Aventis Enters into Licensing Agreement with Kyowa Hakko Kirin ...........................67 6.3.3 GlaxoSmithKline Enters into Licensing Agreement with ChemoCentryx ...............................67

7 Gastrointestinal Therapeutics in Major Developed Markets – Appendix ...............................................68 7.1 All Pipeline Drugs by Phase ......................................................................................................68

7.1.1 Discovery .........................................................................................................................68 7.1.2 Preclinical ........................................................................................................................68 7.1.3 IND/CTA-filed ...................................................................................................................69


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Table of Contents

7.1.4 Phase I .............................................................................................................................70 7.1.5 Phase II ............................................................................................................................71 7.1.6 Phase III ...........................................................................................................................73 7.1.7 Pre-Registration ...............................................................................................................73 7.1.8 Undisclosed......................................................................................................................74

7.2 Market Forecasts to 2019 ........................................................................................................74 7.2.1 Major Developed Markets ................................................................................................74 7.2.2 US....................................................................................................................................75 7.2.3 Canada ............................................................................................................................76 7.2.4 UK ...................................................................................................................................77 7.2.5 France .............................................................................................................................78 7.2.6 Germany ..........................................................................................................................79 7.2.7 Italy .................................................................................................................................80 7.2.8 Spain ...............................................................................................................................81 7.2.9 Japan ...............................................................................................................................82

7.3 Market Definitions ...................................................................................................................83 7.4 Abbreviations ..........................................................................................................................83 7.5 Sources....................................................................................................................................85 7.6 Research Methodology ............................................................................................................87

7.6.1 Coverage .........................................................................................................................87 7.6.2 Secondary Research .........................................................................................................87 7.6.3 Primary Research .............................................................................................................88 7.6.4 Therapeutic Landscape .....................................................................................................88 7.6.5 Geographical Landscape ..................................................................................................91 7.6.6 Pipeline Analysis...............................................................................................................91

7.7 Expert Panel Validation ............................................................................................................91 7.8 Contact Us ...............................................................................................................................91 7.9 Disclaimer................................................................................................................................91


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Table of Contents

1.1 List of Tables

Table 1: Gastrointestinal Therapeutics Market, Irritable Bowel Syndrome, Classification, 2009 ..............12 Table 2: Gastrointestinal Therapeutics Market, Major Developed Markets, Treatment Recommendations

for Irritable Bowel Syndrome, 2009 .........................................................................................16 Table 3: Gastrointestinal Therapeutics Market, Major Developed Markets, Classification of Ulcerative

Colitis, 2004 ............................................................................................................................16 Table 4: Gastrointestinal Therapeutics Market, Major Developed Markets, Diagnosis of Ulcerative Colitis,

2007 .......................................................................................................................................18 Table 5: Gastrointestinal Therapeutics Market, Major Developed Markets, Difference Between Ulcerative

Colitis and Crohn’s Disease, 2007 ............................................................................................19 Table 6: Gastrointestinal Therapeutics Market, Major Developed Markets, Treatment Options of

Ulcerative Colitis, 2011............................................................................................................21 Table 7: Gastrointestinal Therapeutics Market, Major Developed Markets, Classification of Crohn’s

Disease, 2013..........................................................................................................................21 Table 8: Gastrointestinal Therapeutics Market, Major Developed Markets, Symptoms of Crohn’s Disease,

2012 .......................................................................................................................................22 Table 9: Gastrointestinal Therapeutics Market, Major Developed Markets, Treatment Options for

Crohn’s Disease , 2009 ............................................................................................................25 Table 10: Gastrointestinal Therapeutics Market, Global, Pipeline (Discovery), 2013 .................................68 Table 11: Gastrointestinal Therapeutics Market, Global, Pipeline (Preclinical), 2013 ................................68 Table 12: Gastrointestinal Therapeutics Market, Global, Pipeline (IND/CTA-filed), 2013...........................69 Table 13: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase I), 2013 .....................................70 Table 14: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase II), 2013 ....................................71 Table 15: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase III), 2013 ...................................73 Table 16: Gastrointestinal Therapeutics Market, Global, Pipeline (Pre-Registration), 2013 .......................73 Table 17: Gastrointestinal Therapeutics Market, Global, Pipeline (Undisclosed), 2012 .............................74 Table 18: Gastrointestinal Therapeutics Major Developed Markets, Irritable Bowel Syndrome, Market

Forecast, 2012–2019 ...............................................................................................................74 Table 19: Gastrointestinal Therapeutics Market, Major Developed Markets, Ulcerative Colitis, Market

Forecast, 2012–2019 ...............................................................................................................75 Table 20: Gastrointestinal Therapeutics Market, Major Developed Markets, Crohn’s Disease, Market

Forecast, 2012–2019 ...............................................................................................................75 Table 21: Gastrointestinal Therapeutics Market, US, Irritable Bowel Syndrome, Market Forecast, 2012–

2019 .......................................................................................................................................75 Table 22: Gastrointestinal Therapeutics Market, US, Ulcerative Colitis, Market Forecast, 2012–2019 .......76 Table 23: Gastrointestinal Therapeutics Market, US, Crohn’s Disease, Market Forecast, 2012–2019 ........76 Table 24: Gastrointestinal Therapeutics Market, Canada, Irritable Bowel Syndrome, Market Forecast,

2012–2019 .............................................................................................................................76 Table 25: Gastrointestinal Therapeutics Market, Canada, Ulcerative Colitis, Market Forecast, 2012–201977 Table 26: Gastrointestinal Therapeutics Market, Canada, Crohn’s Disease, Market Forecast, 2012–2019 .77 Table 27: Gastrointestinal Therapeutics Market, UK, Irritable Bowel Syndrome, Market Forecast, 2012–

2019 .......................................................................................................................................77 Table 28: Gastrointestinal Therapeutics Market, UK, Ulcerative Colitis, Market Forecast, 2012–2019.......78 Table 29: Gastrointestinal Therapeutics Market, UK, Crohn’s Disease, Market Forecast, 2012–2019 ........78 Table 30: Gastrointestinal Therapeutics Market, France, Irritable Bowel Syndrome, Market Forecast,

2012–2019 .............................................................................................................................78 Table 31: Gastrointestinal Therapeutics Market, France, Ulcerative Colitis, Market Forecast, 2012–2019 .79 Table 32: Gastrointestinal Therapeutics Market, France, Crohn’s Disease, Market Forecast, 2012–2019 ..79 Table 33: Gastrointestinal Therapeutics Market, Germany, Irritable Bowel Syndrome, Market Forecast,

2012–2019 .............................................................................................................................79 Table 34: Gastrointestinal Therapeutics Market, Germany, Ulcerative Colitis, Market Forecast, 2012–2019

...............................................................................................................................................80 Table 35: Gastrointestinal Therapeutics Market, Germany, Crohn’s Disease, Market Forecast, 2012–2019

...............................................................................................................................................80 Table 36: Gastrointestinal Therapeutics Market, Italy, Irritable Bowel Syndrome, Market Forecast, 2012–

2019 .......................................................................................................................................80 Table 37: Gastrointestinal Therapeutics Market, Italy, Ulcerative Colitis, Market Forecast, 2012–2019 ....81 Table 38: Gastrointestinal Therapeutics Market, Italy, Crohn’s Disease, Market Forecast, 2012–2019 ......81


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Table of Contents

Table 39: Gastrointestinal Therapeutics Market, Spain, Irritable Bowel Syndrome, Market Forecast, 2012–2019 .......................................................................................................................................81

Table 40: Gastrointestinal Therapeutics Market, Spain, Ulcerative Colitis, Market Forecast, 2012–2019...82 Table 41: Gastrointestinal Therapeutics Market, Spain, Crohn’s Disease, Market Forecast, 2012–2019 ....82 Table 42: Gastrointestinal Therapeutics Market, Japan, Irritable Bowel Syndrome, Market Forecast, 2012–

2019 .......................................................................................................................................82 Table 43: Gastrointestinal Therapeutics Market, Japan, Ulcerative Colitis, Market Forecast, 2012–2019 ..83 Table 44: Gastrointestinal Therapeutics Market, Japan, Crohn’s Disease, Market Forecast, 2012–2019 ....83


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Table of Contents

1.2 List of Figures

Figure 1: Gastrointestinal Therapeutics Market, Major Developed Markets, Treatment Algorithm of Ulcerative Colitis, 2007............................................................................................................20

Figure 2: Gastrointestinal Therapeutics Market, Global, Sales of Amitiza ($m), 2006–2012 .....................27 Figure 3: Gastrointestinal Therapeutics Market, Global, Sales of Humira ($bn), 2006–2012 .....................28 Figure 4: Gastrointestinal Therapeutics Market, Global, Sales of Remicade ($bn), 2006–2012 .................29 Figure 5: Gastrointestinal Therapeutics Market, Global, Sales of Simponi ($m), 2009–2012 ....................30 Figure 6: Gastrointestinal Therapeutics Market, Global, Sales of Cimzia ($m), 2008–2012 .......................31 Figure 7: Gastrointestinal Therapeutics Market, Global, Sales of Tysabri ($m), 2006–2012 ......................32 Figure 8: Gastrointestinal Therapeutics Market, Global, Irritable Bowel Syndrome, Pipeline, 2013 ..........35 Figure 9: Gastrointestinal Therapeutics Market, Global, Irritable Bowel Syndrome, Pipeline by Molecule

Type, 2013 ..............................................................................................................................36 Figure 10: Gastrointestinal Therapeutics Market, Global, Irritable Bowel Syndrome, Pipeline by Mechanism

of Action, 2012 .......................................................................................................................38 Figure 11: Gastrointestinal Therapeutics Market, Global, Ulcerative Colitis, Pipeline, 2013 .......................40 Figure 12: Gastrointestinal Therapeutics Market, Global, Ulcerative Colitis, Pipeline by Molecule Type,

2013 .......................................................................................................................................41 Figure 13: Gastrointestinal Therapeutics Market, Global, Ulcerative Colitis, Pipeline by Mechanism of

Action, 2013 ...........................................................................................................................43 Figure 14: Gastrointestinal Therapeutics Market, Global, Crohn’s Disease, Pipeline, 2013 .........................45 Figure 15: Gastrointestinal Therapeutics Market, Global, Crohn’s Disease, Pipeline by Molecule Type, 2013

...............................................................................................................................................46 Figure 16: Gastrointestinal Therapeutics Market, Global, Crohn’s Disease, Pipeline by Mechanism of

Action, 2013 ...........................................................................................................................48 Figure 17: Gastrointestinal Therapeutics Market, Major Developed Markets, Market Size ($bn), 2012–2019

...............................................................................................................................................51 Figure 18: Gastrointestinal Therapeutics Market, US, Market Size ($bn), 2012–2019 ................................53 Figure 19: Gastrointestinal Therapeutics Market, Top Five European Countries, Market Size ($bn), 2012–

2019 .......................................................................................................................................55 Figure 20: Gastrointestinal Therapeutics Market, Canada, Market Size ($m), 2012–2019 ..........................57 Figure 21: Gastrointestinal Therapeutics Market, Japan, Market Size ($m), 2012–2019.............................59 Figure 22: Gastrointestinal Therapeutics Market, Global, Deals, 2006–2013 .............................................63 Figure 23: Gastrointestinal Therapeutics Market, Global, Co-Development Deals, 2006–2013 ..................64 Figure 24: Gastrointestinal Therapeutics Market, Global, Licensing Deals, 2006–2013 ..............................66 Figure 25: GBI Research Market Forecasting Model .................................................................................90


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Gastrointestinal Therapeutics in Major Developed Markets – Introduction

2 Gastrointestinal Therapeutics in Major Developed Markets – Introduction

2.1 Irritable Bowel Syndrome

2.1.1 Classification

In terms of severity level, Irritable Bowel Syndrome (IBS) can be mild, moderate or severe. Mild symptoms, which occur infrequently, sometimes interfere with normal daily functioning. Moderate symptoms are more intense, occur more frequently, and often interfere with daily activities, whereas severe symptoms chronically interfere with daily functioning.

Classification is based on Rome III criteria along with patient’s stool characteristics, as outlined in the following table.

Table 1: Gastrointestinal Therapeutics Market, Irritable Bowel Syndrome, Classification, 2009

IBS-D IBS-C IBS-M

Loose stools >XX% of the time and hard stools <XX% of the time

Hard stools >XX% of the time and loose stools <XX% of the time

Both hard and soft stools >XX% of the time

Up to XX of cases Up to XX of cases Both hard and soft stools >XX% of the time

More common in men Up to XX of cases Between XX and one half of cases

Source: WGO, 2009a

IBS-D: Irritable Bowel Syndrome Diarrhea

IBS-C: Irritable Bowel Syndrome Constipation

IBS-M: Irritable Bowel Syndrome Mixed

2.1.2 Symptoms

The symptoms of IBS include abdominal pain or discomfort, changes in bowel habits, the passing of mucus along with stool, abdominal bloating or distension and a feeling of incomplete defecation. For IBS to be diagnosed, all of these symptoms should occur at least three times a month. The bowel movements usually occur more or less often than normal and with stool that appears looser and more watery, or harder and more lumpy than usual. The symptoms are usually long-term, which may occur in episodes, may be meal-related, and sometimes may even lead to severe intestine infection. Sometimes, IBS symptoms may also get confused or overlapped with gastroesophageal reflux disease or dyspepsia.

2.1.3 Etiology

IBS is a multifactorial functional disorder related to the following genetic, environmental and psychological factors.

Diet

Lactose intolerance, as well as intolerance to sorbitol or fructose, has been implicated in IBS. The hypersensitive guts of patients with IBS show exaggerated responses to the gaseous and fluid distention caused by incomplete absorption of carbohydrate.

Psychological factors

Intense emotional states, such as stress and anxiety, can trigger chemical changes that interfere with the normal functioning of the digestive system. Anger is closely associated with enhanced contractile activity in the sigmoid-rectum area, whereas reduced motility is documented in cases of fear. Anxiety can induce rapid small bowel transit and enhanced stool frequency. Depression is associated with delayed small bowel and colonic transit. Common characteristics of IBS patients are the pathologic gradation of visceral perception, endogenous pain facilitation, and a reduced threshold for pain.


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Gastrointestinal Therapeutics in Major Developed Markets – Pipeline Analysis

4 Gastrointestinal Therapeutics in Major Developed Markets – Pipeline Analysis

4.1 Irritable Bowel Syndrome

4.1.1 Overall Pipeline

The current developmental pipeline for IBS drugs is moderate, with a total of XX drug candidates in various stages of clinical development. From a total of XX pipeline products in active development, XX% are in Phase XX% in Phase XX, XX% are in Phase XX and XX% are in the pre-clinical stage (Figure XX, Panel A). A significant proportion – XX% – of pipeline products in the clinical stages of development are novel, whereas only XX% of molecules are generic (Figure XX, Panel XX). The route of administration for the majority of pipeline drugs is oral (XX%), followed by intravenous (XX%) and intradermal/subcutaneous (XX%). The share of all other routes of administration is displayed in Figure XX, Panel C.

A substantial proportion of pipeline products in the clinical stages of development are small molecules, which account for XX% of the overall pipeline, irrespective of the stage of development followed by peptides as illustrated in Figure XX, Panel XX. In each phase, the pipeline encompasses a diverse range of molecules, which act upon various signaling targets. The individual molecular targets that currently dominate the IBS pipeline are XX-Hydroxytryptamine modulators, followed by the Neurokinin receptor antagonist.

XX series of tables containing an exhaustive list of all pipeline molecules, along with their respective companies and molecular targets is available in the appendix, with a separate table for each stage of development.

A substantial proportion of pipeline products in the clinical stages of development are small molecules


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Figure 8: Gastrointestinal Therapeutics Market, Global, Irritable Bowel Syndrome, Pipeline, 2013

B) IBS therapeutics pipeline by program type

C) IBS therapeutics pipeline by route of administration

A) IBS therapeutics pipeline by stage

Novel

Genericn = XX

Intradermal

Intravenous

Oral

Subcutaneous

n = XX

Discovery

Preclinical

Phase I

Phase II

Phase III

Pre-registration

n = XX



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4.1.2 Pipeline Analysis by Molecule Type

The pipeline for IBS is dominated by small molecules, with XX drug candidates or XX% of the overall pipeline (Figure 9, Panel A). When segregated on the basis of stage of development, the share of small molecules is highest in the Phase XX stage, which accounts for XX%, followed by Phase XX with XX%, preclinical and Phase XX with XX% each. Of the XX product candidates that are currently in Phase XX trials, XX molecule falls under the small molecule category (Figure 9, Panel B).

In addition to small molecules, peptides also occupy a significant share with XX molecules or XX% of the overall pipeline (Figure 9, Panel A). There are number of molecules with a status of undisclosed nature of molecule type. These molecules account for around XX% of the overall pipeline.

Figure 9: Gastrointestinal Therapeutics Market, Global, Irritable Bowel Syndrome, Pipeline by Molecule Type, 2013

A) IBS therapeutics pipelineby molecule type

B) IBS therapeutics pipeline by molecule type and by Phase

Pip

elin

e m

olec

ules

(num

ber)

Small molecule Peptide Undisclosed Vaccine

Peptide

Small molecule

Undisclosed

Vaccine

n = XX



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Gastrointestinal Therapeutics in Major Developed Markets – Appendix

7 Gastrointestinal Therapeutics in Major Developed Markets – Appendix

7.1 All Pipeline Drugs by Phase

7.1.1 Discovery

Table 10: Gastrointestinal Therapeutics Market, Global, Pipeline (Discovery), 2013

Product name Company Indication

Disulfide Rich Peptides For Inflammatory Bowel Diseases Protagonist Therapeutics Inc. IBS

LIBS Respiratorius AB IBS

Nexvax-2 ImmusanT, Inc. IBS

Adalimumab biosimilar Alteogen Inc. UC

ONS-3015 Oncobiologics, Inc. UC

ROR-gamma program Karo Bio AB UC

Adalimumab biosimilar Celltrion, Inc. CD

SQ-641 Sequella, Inc. CD

Source: GBI Research, Proprietary Pipeline Products Database [accessed September 10, 2013]

7.1.2 Preclinical

Table 11: Gastrointestinal Therapeutics Market, Global, Pipeline (Preclinical), 2013


M-0012 Shire Plc IBS

M-0014 Shire Plc. IBS

MDT-006 MicroDose Therapeutx, Inc. IBS

PBI-1737 ProMetic Life Sciences Inc. IBS

RQ-00202730 RaQualia Pharma Inc. IBS

RQ-00310941 RaQualia Pharma Inc. IBS

YH-12852 Yuhan Corporation IBS

mesalamine + N-acetylcysteine Altheus Therapeutics, Inc. UC

ANs-42 Advancell UC

AW/EPO-002 INOXIA Lifesciences GmbH UC

AW/EPO-003 INOXIA Lifesciences GmbH UC

AW/EPOPD-01 INOXIA Lifesciences GmbH UC



BLI-1006 BioLite, Inc. UC

ESN-282 Euroscreen S.A. UC

GP-1200 GP Pharm, S.A. UC

Iacvita Medestea Research & Production S.p.A. UC

IP-1510 Itis Pharmaceuticals Pty Ltd. UC

Leukothera Actinobac Biomed, Inc. UC

MD-707 Effimune UC

PH-46A Trino Therapeutics Ltd UC

Prozumab ProtAb Ltd UC


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QBECO SSI Qu Biologics Inc. UC

TP-07 Tillotts Pharma AG UC

AbGn-168H AbGenomics International, Inc. CD

ABK-16 Abkine Pharmaceuticals, Inc. CD

AMX-256 Amunix, Inc. CD

ANs-42 Advancell CD

AZ-17 Allozyne, Inc. CD

BL-5040 BioLineRx, Ltd. CD

CT-637 Creabilis Therapeutics S.r.l. CD

ITP-01 Immunotherapix SAS CD

Interleukin-6 Disulfide Rich Peptides Antagonist Program Protagonist Therapeutics Inc. CD

Interleukin-17 Antagonist Ensemble Therapeutics Corporation CD

Leukothera Actinobac Biomed, Inc. CD

MP-196 Effimune CD

PBI-1737 ProMetic Life Sciences Inc. CD

PH-46A Trino Therapeutics Ltd CD

SelK-2 Selexys Pharmaceuticals Corporation CD

STNM-01 Stelic Institute & Co. CD

Xpro-1595 Xencor, Inc. CD


7.1.3 IND/CTA-filed

Table 12: Gastrointestinal Therapeutics Market, Global, Pipeline (IND/CTA-filed), 2013


Adalimumab Biosimilar AlphaMab Co., Ltd UC



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7.1.4 Phase I

Table 13: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase I), 2013


ASP-7147 Drais Pharmaceuticals, Inc. IBS

DA-6886 Dong-A Pharmaceutical Co., Ltd. IBS

larazotide acetate Alba Therapeutics Corporation IBS

mexiletine hydrochloride Mayo Clinic IBS

ROSE-010 Rose Pharma A/S IBS

AVX-470 Avaxia Biologics, Inc. UC

GS-5745 Gilead Sciences, Inc. UC

HE-3286 Harbor Therapeutics, Inc. UC

infliximab biosimilar Celltrion, Inc. UC

infliximab biosimilar Aprogen, Inc. UC

infliximab biosimilar Pfizer Inc. UC

LMW Heparin MMX Cosmo Pharmaceuticals S.p.A UC

ORE-1001 Ore Pharmaceuticals Inc UC

SAR-252067 Sanofi UC

SP-333 Synergy Pharmaceuticals, Inc. UC

rifabutin + clarithromycin + clofazimine RedHill Biopharma Ltd. CD

Allogenic Adipose-Derived Stem Cells Anterogen Co., Ltd. CD

AMG-139 Amgen Inc. CD

Atrosab Baliopharm AG CD

bertilimumab iCo Therapeutics Inc. CD

CrohnsVax Immune Response BioPharma, Inc. CD

CyCron Sigmoid Pharma Ltd. CD

larazotide acetate Alba Therapeutics Corporation CD

QBECO SSI Qu Biologics Inc. CD

SAR-252067 Sanofi CD

semapimod Cytokine PharmaSciences, Inc. CD

SGX-203 Soligenix, Inc. CD

SYN-1002 CLL Pharma CD

VGX-1027 Inovio Pharmaceuticals, Inc. CD

ZP-1848 Zealand Pharma A/S CD

zucapsaicin Winston Pharmaceuticals, Inc. CD



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7.1.5 Phase II

Table 14: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase II), 2013


Mosapride + Bacillus subtilis + Streptococcas feacium Hanmi Pharmaceuticals, Co. Ltd. IBS

AST-120 Kureha Corporation IBS

AZD-1722 AstraZeneca PLC IBS

crofelemer Napo Pharmaceuticals, Inc. IBS

DSP-6952 Dainippon Sumitomo Pharma Co., Ltd. IBS

elobixibat Ferring Pharmaceuticals, Inc. IBS

LX-1031 Lexicon Pharmaceuticals, Inc. IBS

LX-1033 Lexicon Pharmaceuticals, Inc. IBS

ONO-2952 Ono Pharmaceutical Co., Ltd. IBS

plecanatide Synergy Pharmaceuticals, Inc. IBS

rifaximin Alfa Wassermann S.p.A IBS

solabegron hydrochloride AltheRx Pharmaceuticals, Inc. IBS

mesalamine + N-acetylcysteine Altheus Therapeutics, Inc. UC

metenkefalin + tridecactide Farmacija d.o.o. Tuzla UC

AJG-511 Ajinomoto Pharmaceuticals Co., Ltd. UC

AJM-300 Ajinomoto Pharmaceuticals Co., Ltd. UC

AM-3301 Amalyte Pharmaceuticals, LLC UC

AMG-181 Amgen Inc. UC

anrukinzumab Pfizer Inc. UC

Anti-CD3 Mab NasVax Ltd. UC

ASP-3291 Drais Pharmaceuticals, Inc. UC

bertilimumab iCo Therapeutics Inc. UC

BL-7040 BioLineRx, Ltd. UC

budesonide Cosmo Pharmaceuticals S.p.A UC

catridecacog Novo Nordisk A/S UC

CyCol Sigmoid Pharma Ltd. UC

dersalazine Palau Pharma, S.A. UC

eldelumab Bristol-Myers Squibb Company UC

etrolizumab Genentech, Inc. UC

GLPG-0974 Galapagos NV UC

GSK-1399686 GlaxoSmithKline plc UC

GSK-2245840 GlaxoSmithKline plc UC

GWP-42003 GW Pharmaceuticals plc UC

interferon beta-1a Biogen Idec Inc. UC

LMW Heparin MMX Cosmo Pharmaceuticals S.p.A UC

LT-02 LIPID THERAPEUTICS GmbH UC

MultiStem Athersys, Inc. UC

Natura-Alpha Natrogen Therapeutics International, Inc UC

OvaSave TxCell SA UC


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PC-SOD LTT Bio-Pharma Co., Ltd. UC

PF-00547659 Pfizer Inc. UC

telotristat etiprate Lexicon Pharmaceuticals, Inc. UC

tralokinumab MedImmune, LLC UC

TSO Coronado Biosciences, Inc. UC

vatelizumab Sanofi UC

VB-201 Vascular Biogenics Ltd. UC

RPC-1063 Receptos, Inc. UC

vidofludimus 4SC AG UC

metenkefalin + tridecactide Farmacija d.o.o. Tuzla CD

Alequel Enzo Biochem, Inc. CD

AMG-181 Amgen Inc. CD

cenplacel-L Celgene Corporation CD

clazakizumab Alder Biopharmaceuticals Inc. CD

eldelumab Bristol-Myers Squibb Company CD

FFP-102 FF Pharmaceuticals BV CD

GED-0301 Giuliani S.p.A. CD

HMPL-004 Hutchison MediPharma Limited CD

laquinimod sodium Teva Pharmaceutical Industries Limited CD

mesalamine CR Zeria Pharmaceutical Co Ltd CD

NI-0401 NovImmune SA CD

NN-8828 Novo Nordisk A/S CD

OvaSave TxCell SA CD

PF-00547659 Pfizer Inc. CD

PF-04236921 Pfizer Inc. CD

rifaximin Alfa Wassermann S.p.A CD

teduglutide NPS Pharmaceuticals, Inc. CD

tetomilast Otsuka Holdings Co., Ltd. CD

TNF-Kinoid Neovacs SA CD

tofacitinib Pfizer Inc. CD

TRK-170 Toray Industries, Inc. CD

TSO Coronado Biosciences, Inc. CD

vidofludimus 4SC AG CD



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7.1.6 Phase III

Table 15: Gastrointestinal Therapeutics Market, Global, Pipeline (Phase III), 2013


asimadoline Tioga Pharmaceuticals, Inc. IBS

dexloxiglumide Rottapharm|Madaus IBS

eluxadoline Furiex Pharmaceuticals, Inc. IBS

ibodutant A. Menarini Industrie Farmaceutiche Riunite Srl IBS

linaclotide Ironwood Pharmaceuticals, Inc. IBS

rifaximin Alfa Wassermann S.p.A IBS

budesonide AstraZeneca PLC UC

budesonide Dr. Falk Pharma GmbH UC

DIMS-0150 InDex Pharmaceuticals AB UC

HMPL-004 Hutchison MediPharma Limited UC

infliximab Johnson & Johnson UC

levocarnitine propionate hydrochloride Sigma-Tau S.p.A. UC

mesalamine Aptalis Pharma Inc. UC

mesalamine CR Zeria Pharmaceutical Co Ltd UC

mesalamine ER Giuliani S.p.A. UC

tofacitinib Pfizer Inc. UC

adalimumab AbbVie Inc. CD

AJM-300 Ajinomoto Pharmaceuticals Co., Ltd. CD

budesonide AstraZeneca PLC CD

infliximab Johnson & Johnson CD

metronidazole S.L.A. Pharma AG CD

remestemcel-L Osiris Therapeutics, Inc. CD

ustekinumab Johnson & Johnson CD

vedolizumab Takeda Pharmaceutical Company Limited CD


7.1.7 Pre-Registration

Table 16: Gastrointestinal Therapeutics Market, Global, Pipeline (Pre-Registration), 2013


mesalamine Tillotts Pharma AG UC

infliximab biosimilar Celltrion, Inc. CD

vedolizumab Takeda Pharmaceutical Company Limited CD



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7.1.8 Undisclosed

Table 17: Gastrointestinal Therapeutics Market, Global, Pipeline (Undisclosed), 2012


AM-3301 Amalyte Pharmaceuticals, LLC IBS

GIC-1001 gIcare Pharma Inc IBS

YKP-10811 SK Biopharmaceuticals Co., Ltd. IBS

adalimumab Biosimilar PanPharmaceuticals USA, Inc. UC

alicaforsen sodium Atlantic Healthcare Limited UC

clotrimazole AesRx, LLC. UC

FX-003 Flexion Therapeutics, Inc. UC

GED-0507 Giuliani S.p.A. UC

SD-010 SciDose LLC UC

rifabutin + clarithromycin + clofazimine RedHill Biopharma Ltd. CD

adalimumab biosimilar Celltrion, Inc. CD

ApoCell Enlivex Therapeutics Ltd CD

GLPG-0634 Galapagos NV CD

IBI-303 Innovent Biologics, Inc. CD

IBP-M004-AM Inbiopro Solutions Pvt. Ltd. CD

ORE-1001 Ore Pharmaceuticals Inc CD


7.2 Market Forecasts to 2019

7.2.1 Major Developed Markets

7.2.1.1 Irritable Bowel Syndrome

Table 18: Gastrointestinal Therapeutics Major Developed Markets, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)

Prevalence population ('000)

Prescription population ('000)

ACoT ($)

Revenue ($m)

Source: GBI Research, Proprietary Products Database [accessed October 16, 2013]


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7.2.1.2 Ulcerative Colitis

Table 19: Gastrointestinal Therapeutics Market, Major Developed Markets, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($bn)


7.2.1.3 Crohn’s Disease

Table 20: Gastrointestinal Therapeutics Market, Major Developed Markets, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($bn)


7.2.2 US


Table 21: Gastrointestinal Therapeutics Market, US, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 22: Gastrointestinal Therapeutics Market, US, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($bn)



Table 23: Gastrointestinal Therapeutics Market, US, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($bn)


7.2.3 Canada


Table 24: Gastrointestinal Therapeutics Market, Canada, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 25: Gastrointestinal Therapeutics Market, Canada, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 26: Gastrointestinal Therapeutics Market, Canada, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.4 UK


Table 27: Gastrointestinal Therapeutics Market, UK, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 28: Gastrointestinal Therapeutics Market, UK, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 29: Gastrointestinal Therapeutics Market, UK, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.5 France


Table 30: Gastrointestinal Therapeutics Market, France, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 31: Gastrointestinal Therapeutics Market, France, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 32: Gastrointestinal Therapeutics Market, France, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.6 Germany


Table 33: Gastrointestinal Therapeutics Market, Germany, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 34: Gastrointestinal Therapeutics Market, Germany, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 35: Gastrointestinal Therapeutics Market, Germany, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.7 Italy


Table 36: Gastrointestinal Therapeutics Market, Italy, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 37: Gastrointestinal Therapeutics Market, Italy, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 38: Gastrointestinal Therapeutics Market, Italy, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.8 Spain


Table 39: Gastrointestinal Therapeutics Market, Spain, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 40: Gastrointestinal Therapeutics Market, Spain, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 41: Gastrointestinal Therapeutics Market, Spain, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.2.9 Japan


Table 42: Gastrointestinal Therapeutics Market, Japan, Irritable Bowel Syndrome, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



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Table 43: Gastrointestinal Therapeutics Market, Japan, Ulcerative Colitis, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)



Table 44: Gastrointestinal Therapeutics Market, Japan, Crohn’s Disease, Market Forecast, 2012–2019

2012 2013 2014 2015 2016 2017 2018 2019 CAGR (%)



ACoT ($)

Revenue ($m)


7.3 Market Definitions

The prevalence population is the estimated number of people at any given point of time who are affected by IBS, UC, and CD.

The prescription population refers to the number of patients suffering from IBS, UC, and CD that has been prescribed pharmacological treatments.

7.4 Abbreviations

µg: microgram

ACoT: Annual Cost of Therapy

A4b7: Alpha 4 beta 7

ACG: American College of Gastroenterology

BLA: Biologic License Application

CAGR: Compound Annual Growth Rate

CCR11: Chemokine (C-C Motif) Receptor 11

CCKAR: Cholecystokinin A receptor

CD: Crohn’s Disease

CFTR: Cystic Fibrosis Transmembrane Conductance Regulators

cfu/ml: Colony forming unit per milliliter

CRF: Corticotropin Release Factor

CRP: C - reactive protein

DNA: Deoxyribonucleic Acid

EMA: Endomysial Antibodies


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ENS: Enteric Nervous System

ESR: Erythrocyte Sedimentation Rate

FBC: Full Blood Count

Fc: Fragment crystallizable

GR: Glucocorticoid Receptor

GI: Gastrointestinal

GLP: Glucagon-like Peptide

GSK: GlaxoSmithKline

HMGB: High Mobility Group protein Box

IL-1α: Interleukin-1α

IND/CTA: Investigational New Drug/Clinical Trial Application

IBD: Irritable Bowel Disease

IBS: Irritable Bowel Syndrome

IBS-A/M: Irritable Bowel Syndrome-Alternating/Mixed

IBS-C: Irritable Bowel Syndrome with Constipation

IBS-D: Irritable Bowel Syndrome with Diarrhea

JAK: Janus Kinase

LFA-1: Lymphocyte Function-Associated Antigen 1

LOX: Lipoxygenase

MAP: Mitogen-Activated Protein

MMP: Matrix Metalloproteinases

MAA: Marketing Authorization Application

ml: Milliliter

NFkB: Nuclear Factor Kappa B

NF-KB: Nuclear Factor-Kappa B

NSAID: Non-steroidal Anti-inflammatory Drug

PEG: Polyethylene Glycol

R&D: Research & Development

RNA: Ribonucleic Acid

ROS: Reactive Oxygen Species

SIBO: Small Intestine Bacterial Overgrowth

SSRI: Selective Serotonin Reuptake Inhibitor

TNF-α: Tumor Necrosis Factor-α

TRPV-1: Transient Receptor Potential Vanilloid 1

TCA: Tricyclic Antidepressant

TLR: Toll-like Receptor

TTG: Tissue Transglutaminase

UD: Unit Dose


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UC: Ulcerative Colitis

UCB: Union Chimique Belge

VCAM: Vascular Cell Adhesion Molecule

VLA: Very Late Antigen

US FDA: US Food and Drug Administration

WBC: White Blood Cell

7.5 Sources

Anderson CA, et al. (2011). Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature Genetics; 43(3): 246-252.

Barbara G, et al. (2004). New pathophysiological mechanisms in irritable bowel syndrome. Alimentary Pharmacology & Therapeutics; 20(2): 1-9.

CCFA (2012a). Crohn’s and Colitis Foundation of America. Available from: http://www.ccfa.org/ [Accessed on August 10, 2013]

CCFA (2012b). Crohn’s and Colitis Foundation of America. Available from: http://www.ccfa.org/ [Accessed on August 10, 2013]

Cleveland Clinic, Crohn’s Disease, 2013. Available from: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/crohns-disease/ [Accessed on August 13, 2013]

Corrao G, et al. (1998). Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC). International Journal of Epidemiology; 27(3): 397–404.

Crohn’s and Colitis Foundation of Canada (2012). The impact of Inflammatory Bowel Disease in Canada, 2012 Final Report and Recommendations. Crohn’s and Colitis Foundation of Canada. Available from: http://www.isupportibd.ca/pdf/ccfc-ibd-impact-report-2012.pdf

Crowell MD (2004). Role of serotonin in the Pathophysiology of the irritable bowel syndrome. British Journal of Pharmacology; 141(8): 1285-1293.

Delvaux M, et al. (2002). Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome. Gut; 51:i67–i71.

D'Odorico A, et. al. (2001). Reduced Plasma Antioxidant Concentrations and Increased Oxidative DNA Damage in Inflammatory Bowel Disease. Scandinavian Journal of Gastroenterology; 36 (12):1289-1294

Ekbom A, et al. (1990). Ulcerative colitis and colorectal cancer. The New England Journal of Medicine; 323(18): 1228–1233.

Evangelos J, et al. (2009). Small Intestinal Bacterial Overgrowth: Novel Insight in the Pathogenesis and Treatment of Irritable Bowel Syndrome. Annals of Gastroenterology; 22(2): 1,108–7,471.

Fedorak RN, et al. (2012). Canadian Digestive Health Foundation Public Impact Series 3: Irritable bowel syndrome in Canada. Incidence, prevalence, and direct and indirect economic impact. Canadian Journal of Gastroenterology; 26(5): 252-256.

Fukudo S, et al. (1998). Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut; 42: 845–849.

Halpern GM, et al. (1996). Treatment of irritable bowel syndrome with Lacteol Fort: a randomized, double-blind, cross-over trial. The American Journal of Gastroenterology; 91(8):1579-1585.

Hartley MG, et al. (1992). The rectal mucosa-associated microflora in patients with ulcerative colitis; Journal of Medical Microbiology; 36(2): 96–103.


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Henriksen M, et al. (2006). Ulcerative colitis and clinical course: Results of a 5-year population-based follow-up study (the IBSEN study). Inflammatory Bowel Diseases; 12 (7): 543–550.

Hotoleanu, C (2008). Genetic determination of irritable bowel syndrome. World Journal of Gastroenterology; 14(43): 6636–6640.

Kefalides PT, et al. (2002). Ulcerative colitis: Diagnosis and management: Journal of Clinical Outcomes Management, 8; 40-44.

Kornbluth A, et al. (2004). Ulcerative Colitis Practice Guidelines in Adults (Update): American College of Gastroenterology, Practice Parameters Committee. The American Journal of Gastroenterology; 99: 1,371–1,385.

Langan R, et al. (2007a). Ulcerative Colitis: Diagnosis and Treatment. American Family Physician; 1;76(9):1323-1330.

Langan R, et al. (2007b). Ulcerative Colitis: Diagnosis and Treatment. American Family Physician; 1;76(9):1323-1330.

Langan R, et al. (2007c). Ulcerative Colitis: Diagnosis and Treatment. American Family Physician; 1;76(9):1323-1330.

Lashner BA, (2013). Cleveland Clinic, Disease Management Project, Gastroenterology. Available from: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/crohns-disease/#top

Mitchell SA, et al. (2002). Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study. Gut; 51:567-573.

Miwa H, et al. (2008). Prevalence of irritable bowel syndrome in Japan: Internet survey using Rome III criteria. Journal of Patient Preference and Adherence; 2(2): 143–147.

Molodecky NA, et al. (2012). Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases with Time, Based on Systematic Review. Gastroenterology; 142(1): 46–54.

NICE (2009). Irritable bowel syndrome in adults: Diagnosis and management of irritable bowel syndrome in primary care. National Institute for Health and Clinical Excellence. Available from: http://publications.nice.org.uk/irritable-bowel-syndrome-in-adults-cg61.

NHS (2012). Inflammatory Bowel Disease. National Health Service. Available from: http://www.nhs.uk/conditions/inflammatory-bowel-disease/pages/introduction.aspx [Accessed on August 13, 2013]

Pimentel M. et al. (2004). A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Annals of Rheumatic Disease; 63:450-452.

Quintana A (2012). Clinical Diagnostic Clues in Crohn's Disease: A 41-Year Experience. ISRN Gastroenterology; Article ID 285475.

Seidelin JB, et al. (2013). Mucosal healing in ulcerative colitis: Pathophysiology and pharmacology. Advances in Clinical Chemistry; 59:101-23.

Sidana A, et al. (2012) Pathophysiology of Crohn’s Disease. International Journal of Natural Product Science; Special Issue 1:213

Spiller R, et al. (2007). Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut ;56:1770-1798

The Merck Manual, (2013). Gastrointestinal disorders, Irritable Bowel Disease. Available from: http://www.merckmanuals.com/professional/gastrointestinal_disorders/inflammatory_bowel_disease_ibd/crohn_disease.html

Tocchi A, et al. (1997). Familial and psychological risk factors of ulcerative colitis. Italian Journal of Gastroenterology and Hepatology; 29(5): 395–398.

WebMD (2013). Crohn's Disease Health Center. WebMD. Available from: http://www.webmd.com/ibd-crohns-disease/crohns-disease/5-types-crohns-disease/ [Accessed on September 6, 2013]


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WGO (2009). World Gastroenterology Organization Global Guidelines. World Gastroenterology Organization. Available from: http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/21_inflammatory_bow el_disease. Accessed on August 20, 2013]

Whorwell PJ, et al. (1986) Noncolonic features of irritable bowel syndrome. Gut; 27:37–40. Available from : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1433171/

7.6 Research Methodology

GBI Research’s dedicated research and analysis teams consist of experienced professionals with marketing, market research and consulting backgrounds in the pharmaceutical industry as well as advanced statistical expertise.

GBI Research adheres to the codes of practice of the Market Research Society (www.mrs.org.uk) and the Strategic and Competitive Intelligence Professionals (www.scip.org).

All GBI Research databases are continuously updated and revised.

7.6.1 Coverage

The objective of updating GBI Research coverage is to ensure that it represents the most up-to-date vision of the industry possible.

Changes to the industry taxonomy are built on the basis of extensive research of company, association and competitor sources.

Company coverage is based on three key factors: market capitalization, revenues and media attention/innovation/market potential.

An exhaustive search of 56 member exchanges is conducted and companies are prioritized on the basis of their market capitalization.

The estimated revenue of all major companies, including private and governmental, are gathered and used to prioritize coverage.

Companies that are making the news, or which are of particular interest due to their innovative approach, are prioritized.

GBI Research aims to cover all major news events and deals in the pharmaceutical industry, updated on a daily basis.

The coverage is further streamlined and strengthened with additional inputs from GBI Research’s expert panel (see below).

7.6.2 Secondary Research

The research process begins with exhaustive secondary research on internal and external sources in order to source qualitative and quantitative information relating to each market.

The secondary research sources that are typically referred to include, but are not limited to:

Company websites, annual reports, financial reports, broker reports, investor presentations and SEC filings

Industry trade journals, scientific journals and other technical literature

Internal and external proprietary databases

Relevant patent and regulatory databases

National government documents, statistical databases and market reports

Procedure registries

News articles, press releases and web-casts specific to the companies operating in the market


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7.6.3 Primary Research

GBI Research conducts hundreds of primary interviews a year with industry participants and commentators in order to validate its data and analysis. A typical research interview fulfills the following functions:

It provides first-hand information on the market size, market trends, growth trends, competitive landscape and future outlook.

It helps in validating and strengthening the secondary research findings.

It further develops the analysis team’s expertise and market understanding.

Primary research involves email and telephone interviews as well as face-to-face interviews for each market, category, segment and sub-segment across geographies.

The participants who typically take part in such a process include, but are not limited to:

Industry participants: CEOs, VPs, marketing/product managers, market intelligence managers and national sales managers

Hospital stores, laboratories, pharmacies, distributors and paramedics

Outside experts: Investment bankers, valuation experts, research analysts specializing in specific medical equipment markets

Key opinion leaders: Physicians and surgeons specializing in different therapeutic areas corresponding to different kinds of medical equipment

7.6.4 Therapeutic Landscape

Revenues for each indication, geography-wise, are arrived at by utilizing the GBI Research market forecasting model. The global revenue for each indication is the sum value of revenues of all seven regions.

The ACoT for each indication is arrived at by considering the cost of the drugs, dosage of the drugs and the duration of the therapy.

The generic share of the market for each indication is obtained by calculating the prescription share for generic drugs and the respective cost of treatment.

The treatment usage pattern which includes quantitative data on the diseased population, treatment-seeking population, diagnosed population and treated population for an indication, is arrived at by referring to various sources as mentioned below.

GBI Research uses the epidemiology-based treatment flow model to forecast market size for therapeutic indications.

Epidemiology-Based Forecasting

The forecasting model used at GBI Research makes use of epidemiology data gathered from research publications and primary interviews with physicians to represent the treatment flow patterns for individual diseases and therapies. The market for any disease segment is directly proportional to the volume of units sold and the price per unit.

Sales = Volume of Units sold X Price per Unit

The volume of units sold is calculated on the average dosage regimen for that disease, duration of treatment and number of patients who are prescribed drug treatment (prescription population). Prescription population is calculated as the percentage of population diagnosed with a disease (diagnosis population). Diagnosis population is the population diagnosed with a disease expressed as a percentage of the population that is seeking treatment (treatment-seeking population). Prevalence of a disease (diseased population) is the percentage of the total population who suffer from a disease/condition.


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Data on the treatment seeking rate, diagnosis rate and prescription rate, if unavailable from research publications, are gathered from interviews with physicians and are used to estimate the patient volumes for the disease under consideration. Therapy uptake and compliance data are fitted in the forecasting model to account for patient switching and compliance behavior.

To account for differences in patient affordability of drugs across various geographies, macroeconomic data such as inflation and GDP; and healthcare indicators such as healthcare spending, insurance coverage and average income per individual are used.

ACoT is calculated using product purchase frequency and the average price of the therapy. Product purchase frequency is calculated from the dosage data available for the therapies and drug prices are gathered from public sources.

The epidemiology-based forecasting model uses a bottom-up methodology and it makes use of estimations in the absence of data from research publications. Such estimations may result in a final market value which is different from the actual value. To correct this ‘gap’ the forecasting model uses ‘triangulation’ with the help of base year sales data (from company annual reports, internal and external databases) and sales estimations.

Analogous Forecasting Methodology

Analogous forecasting methodology is used to account for the introduction of new products, patent expiries of branded products and subsequent introduction of generics. Historic data for new product launches and generics penetration are used to arrive at robust forecasts. Increase or decrease of prevalence rates, treatment seeking rate, diagnosis rate and prescription rate are fitted into the forecasting model to estimate market growth rate.

The proprietary model enables GBI Research to account for the impact of individual drivers and restraints in the growth of the market. The year of impact and the extent of impact are quantified in the forecasting model to provide close-to-accurate data sets.

Diseased Population

The diseased population for any indication is the prevalence. The prevalence rates are usually obtained from various journals, online publications, sources such as the World Health Organization (WHO) or associations and foundation websites for that particular disease.

Prescription Population

For any disease, multiple treatment options exist. For example, in cancer treatment various treatment options such as surgery, radiation therapy and drug therapy are available. The prescription population is defined as the number of patients who are prescribed drug therapy. This is calculated as a percentage of the diagnosis population. The prescription population is primarily driven by the age at which the disease is diagnosed, the disease stage, patient health and the cost of drug treatment.


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7.6.4.1 Market Size by Geography

The treatment usage pattern and ACoT in each country has been factored in while deriving the individual country market size.

Forecasting Model for Therapeutic Areas

Figure 25: GBI Research Market Forecasting Model

D is e as e P opu lati onGe ne r al Po pu la tio n 7 43,53 5,04 8

Q uali fyin g c ondition 1 (Ag e/S ex/O c c upa tio n etc )Q uali fyin g c ondition 2 (Ag e/S ex/O c c upa tio n etc )

Prev al e nc e t issu e va lve disea se 0.2% 1,78 4,48 4 Q uali fyin g c ondition (c om plic at ion , s everity)D IS EA SE D P OPU LA T IO N 1,78 4,48 4

T r e atm e n t Flow P atte rn sT rea tm e nt S eeki ng R ate (Sy m ptom s / Dis Awareness ) 89 % 1,58 8,19 1 Diagn os is Rat e ( C lin ical and D ia gn os tic Tes ts ) 75 % 1,19 1,14 3 Pres cr iption R ate (Ph ys ic ian P e rce p t io n, Tr ea tm e nt E ffec tiv e n e ss )

Tis s ue V alve 70 % 83 3,80 0 O th er T reatm ents for Valve (Su rg /M ed/N one ) -

F ulfi llm en tA vaila bi lit y NAW illingn ess to U s e (Pa tient Pe rc ep tions) NAR ead y to U se (S urg ery e l ig ib i lity , R e us e e tc ) NA

Affo rd a bil it y at PriceH E as % of G DP s pendA verag e In c om e (p er ind ividu al)P at ien t O u t-o f -p oc ke t Budg et (A nnu al)

Bu dg et a l loc a tion to o ne-t im e s urgeryBu dg et a l loc a tion to o the r h e alth n eed s

A verag e Pay or Co vera geP at ien t L iabi li tyTarge t Pr ic e (@ 20 % pa t lia b)A SP for Co s t of T hera py

T O TA L P AT IEN T V OLU M E SPro du ct P urch as e Fr equ en c y 1

T OT A L UN IT VO LU M ES

Pr icin g per Un it 18,00 0$ In f lat ionP rice D ec reas e du e to c om pet it ion

M ar k et Valu e

G BI R ese ar ch M a r ket Siz in g M o de l

Source: GBI Research

The figure above represents a typical forecasting model followed in GBI Research. As discussed previously, the model is built on the treatment flow patterns. The model starts with the general population, then diseased population as a percentage of the general population and then follows the treatment seeking population as a percentage of the diseased population and diagnosed population as a percentage of the treatment seeking population. Finally, the total volume of units sold is calculated by multiplying the treated population by the average dosage per year per patient.


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7.6.5 Geographical Landscape

GBI Research analyzes eight major geographies: the US, the top five countries of Europe (the UK, Germany, France, Spain and Italy) Canada and Japan. The total market size for each country is provided which is the sum value of the market sizes of all the indications for that particular country. The maximum and minimum estimated market sizes are then provided by adjusting all variables expected to impact upon the market during the forecast period in order to provide the best and worst-case scenarios.

Articles from research journals and agency publications such as Gastrointestinal, National Institute of Health and ClinicalTrials.gov are the source of data for the estimation of market size and making forecasts.

7.6.6 Pipeline Analysis

This section provides a list of molecules at various stages in the pipeline for various indications. The list is sourced from internal database and validated for the accuracy of phase and mechanism of action at ClinicalTrials.gov and company websites. The section also includes a list of promising molecules which is narrowed down based on the results of the clinical trials at various stages and the novelty of mechanism of action. A heat map, sourced from relevant clinical trials, is provided in order to compare these products to one another in addition to currently marketed products. The latest press releases issued by the company and news reports are also the source of information for the status of the molecule in the pipeline. This list of pipeline molecules, in conjunction with a list of ongoing and completed clinical trials, is analyzed in this section, and a full breakdown of pipeline molecules and clinical trials by Phase, molecule type and molecular target is provided.

7.7 Expert Panel Validation

GBI Research uses a panel of experts to cross verify its databases and forecasts.

GBI Research expert panel comprises marketing managers, product specialists, and international sales managers from pharmaceutical companies, academics from research universities and key opinion leaders from hospitals.

Historic data and forecasts are relayed to GBI Research’s expert panel for feedback and are adjusted in accordance with their feedback.

7.9 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GBI Research.

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