www.visiongain.com

Contents Fe

1.1 Inflammatory Bowel Disease Market Overview

1.2 Aims, Scope and Format of the Report

1.3 Chapter Outlines

1.4 Research and Analysis Methods

2.1 What is Inflammatory Bowel Disease (IBD)?

2.2 Are There Different Types of IBD?

2.3 Signs, Symptoms and Associated Conditions

2.4 What Causes Inflammatory Bowel Disease?

2.5 How Common is Inflammatory Bowel Disease?

3.1 Can IBD be Cured?

3.2 What Are the Medications Used to Treat IBD?

3.2.1 Aminosalicylates – The Most Common Therapy

3.2.2 Corticosteroids – Limited in the Long-Run?

3.2.3 Immunomodulators – Slow to Act?

3.2.4 Monoclonal Antibodies – The Future?

3.2.5 Antibiotics – Do they Really Help?

3.3 Treatment Protocol

4.1 The Inflammatory Bowel Disease Market in 2012: Domination of Biologics and

Aminosalicylates

4.2 Forecast 2013-2023: Any Major Changes Expected?

4.3 Aminosalicylates Forecast 2013-2023: The Work-Horse of IBD Therapy

4.4 Antibiotics Forecast 2013-2023: Will They Still Be Relevant in a Decade?

1. Executive Summary

2. Introduction to the Inflammatory Bowel Disease Market

3. Drug Treatments for Inflammatory Bowel Diseases

4. The World Inflammatory Bowel Disease Market, 2013-2023

www.visiongain.com

Contents 4.5 Biologic Therapies Forecast 2013-2023: Main Driver of Growth

4.6 Corticosteroids Forecast 2013-2023: Continued Insignificance?

4.7 Immunomodulators Forecast 2013-2023

5.1 IBD Drugs – Leading National Markets, 2012

5.2 The US IBD Drug Market, Revenues 2013-2023 – Leader of the Pack

5.2.1 Case Study: What is the Relative Contribution of Ulcerative Colitis and Crohn’s

Disease to Total IBD Spending in the US?

5.3 The Japanese IBD Drug Market, Revenues 2013-2023 – Tomorrow’s Leader?

5.4 The EU-5 IBD Drug Markets, Revenues 2013-2023 – Europe’s Growth Potential

5.5 IBD Drug Markets in BRIC Countries, Revenues 2013-2023 – Vast Potential for Sales

5.5.1 Brazil: Revenues 2013-2023

5.5.2 Russia: Revenues 2013-2023

5.5.3 India: Revenues 2013-2023

5.5.4 China: Revenues 2013-2023

6.1 Humira (AbbVie) - The Leading Therapy

6.1.1Humira: Forecast and Analysis, 2013-2023

6.2 Remicade (Janssen Biotech) – A Worthy Challenger?

6.2.1Remicade: Forecast and Analysis, 2013-2023

6.3 Asacol (Warner Chilcott) - The Best Mesalazine Formulation?

6.3.1Asacol: Forecast and Analysis, 2013-2023

6.4 Pentasa (Shire USA) – When Will a Generic Substitute Arrive?

6.4.1 Pentasa: Forecast and Analysis, 2013-2023

6.5 Lialda (Shire USA) – What Potential for that Medication?

6.5.1 Lialda: Forecast and Analysis, 2013-2023

6.6 Tysabri (Elan Pharmaceuticals) – Will Side Effects Prove Too Much?

6. Market Prospects for Leading IBD Drugs, 2013-2023

5. Leading National Markets, 2013-2023

www.visiongain.com

Contents 6.6.1 Tysabri: Forecast and Analysis, 2013-2023

6.7 Xifaxan (Salix Pharmaceuticals)

6.7.1 Xifaxan: Forecast and Analysis, 2013-2023

6.8 Cimzia (UCB Inc.) – Approved in Only a Handful of Countries

6.8.1 Cimzia: Forecast and Analysis, 2013-2023

6.9 Entocort (AstraZeneca) – Prominent Steroid Treatment

6.9.1 Entocort: Forecast and Analysis, 2013-2023

6.10 Neoral (Novartis) – A Widely Used Immunosuppressant

6.10.1 Neoral: Forecast and Analysis, 2013-2023

6.11 Medrol (Pfizer Inc.) – Another Leading Steroid

6.11.1 Medrol: Forecast and Analysis, 2013-2023

6.12 Canasa/Salofalk (Aptalis Pharmaceuticals) – A Slow Decline

6.12.1 Canasa/Salofalk: Forecast and Analysis, 2013-2023

6.13 Apriso (Salix Pharmaceuticals) – A Serious Challenger to Asacol?

6.13.1 Apriso: Forecast and Analysis, 2013-2023

6.14 Azulfidine (Pfizer Inc.) – What Scope for Revenue Growth?

6.14.1 Azulfidine: Forecast and Analysis, 2013-2023

7.1 Interleukin (IL) Inhibitors – One of the Main Areas of Innovation

7.1.1 Profile: Vidofludimus (4SC)

7.2 Cell-Adhesion Molecule (CAM) Inhibitors – A Promising Avenue

7.2.1 Profile: Etrolizumab (Roche)

7.3 TNF-α Inhibitors – A Tried and Tested Target

7.3.1 Profile: Ozoralizumab (Ablynx)

7.4 Stem Cell Therapies – Basis for a Cure?

7.4.1 Profile: Remestemcel-L (Osiris Therapeutics)

7.5 Janus Kinase (JAK) Inhibitors – More Targets to Hit

7.5.1 Profile: Tasocitinib (Pfizer)

7.6 Immunomodulators – Will They Live Up To the Hype?

7. The R&D Pipeline for Inflammatory Bowel Disease, 2013

www.visiongain.com

Contents 7.6.1 Profile: ZP1848 (Zealand Pharma)

7.7 Chemokine Receptors – Potential Exists

7.7.1 Profile: Vercirnon (Chemcentryx/GSK)

7.8 Antioxidants and Barrier Function

7.8.1 Profile: Tetomilast (Otsuka) – The Future of IBD Treatment?

8.1 SWOT and STEP Analysis of the IBD Market

8.2 What Factors Will Drive the IBD Market?

8.2.1 Increasing Disease Incidence

8.2.2 Better Diagnosis

8.2.3 Nature of the Disease

8.2.4 Delivery Systems

8.2.5 Biological Drugs

8.2.6 Socioeconomic Costs of IBD

8.3 What Factors Will Restrain the Market?

8.3.1 Lack of Understanding of Disease Aetiology

8.3.2 Compliance

8.3.3 Limits of Biologics

8.3.4 A Cure or Vaccine

8.3.5 The Possible Development of Alternative Treatments

8.3.6 Surgery – When Other Options Fail

9.1 The Largest Companies by Revenue

9.2 AbbVie – The Leader in a Highly Profitable Area

9.3 Janssen Biotech – Tomorrow’s Powerhouse?

9.4 Warner Chilcott – A Strong Competitor

8. Drivers and Restraints in the Inflammatory Bowel Disease Drug Industry and Market, 2013-2023

9. Leading Companies in the IBD Market, 2013

www.visiongain.com

Contents 9.5 Shire Pharmaceuticals – Still a Major Player in the Future?

10.1 Dr Qamar ul Arfin, Gastroenterologist, Aga Khan University Hospital, Karachi, Pakistan

10.1.1 On Antibiotics in Treating IBD

10.1.2 On the Emergence of Biologic Therapies

10.1.3 On IBD in the Pakistani Context

10.1.4 On Any Preventative Measures that Can Be Taken

10.2 Professor John Hermon-Taylor, King’s College London

10.2.1 The Significance of MAP in Crohn’s

10.2.2 Rising Incidence of IBD

10.2.3 Defining IBD

10.2.4 Timeframe of MAP Vaccine

10.2.5 Antibiotic Activity of Other Crohn’s Treatments

10.2.6 Alternative Treatments

10.2.7 Ethics of Crohn’s Drug Development

10.2.8 The Impact of a Vaccine on the Market

10.2.9 On Claims that MAP is Not Implicated in CD

10.3 Professor Thomas Barody, Director, Centre for Digestive Diseases, Sydney

10.3.1 Mycobacterium Avium Paratuberculosis (MAP) Infection and IBD Aetiology

10.3.2 IBD and HIV/AIDS

10.3.3 Monoclonal Antibodies and Immunosuppressant Treatments

10.3.4 Potential Cure?

10.3.5 Remicade and MAP

10.3.6 Genotyping

10.3.7 Crohn’s vs. Colitis

10.3.8 Future Therapies

10.3.9 The Potential and Future of Myoconda

10. Research Interviews

www.visiongain.com

Contents

11.1 IBD Market to Expand from 2013 to 2023

11.2 Aminosalicylates and Other Non-Biologic Treatments

11.3 Biologic Treatments

11.4 Improvements Needed in IBD Treatments

11.5 Future IBD Treatments: R&D Efforts Look Promising

11.6 The IBD Sector: Looking to the Future with Confidence

11. Conclusions

www.visiongain.com

Contents

Table 2.1 World Incidence Rates for IBD, 2013

Table 2.2 Geographical Variations in the Incidence of IBD, 2013

Table 3.1 Other Drug Types Used to Treat IBD, 2013

Table 4.1 Global IBD Drug Sales ($m), Annual Growth Rates (%) and Market Shares (%) by

Segment, 2011 and 2012

Table 4.2 Global IBD Drug Market Forecast ($m), 2012-2023

Table 4.3 Global IBD Drug Forecast by Drug Category ($m), 2012-2023

Table 4.4 Global IBD Drug Market Drivers and Restraints, 2012-2023

Table 4.5 Global Aminosalicylates Forecast ($m), 2012-2023

Table 4.6 Global Aminosalicylates Drivers and Restraints, 2012-2023

Table 4.7 Global Antibiotics Forecast ($m), 2012-2023

Table 4.8 Global Antibiotics Drivers and Restraints, 2012-2023

Table 4.9 Global Biologic Therapies Forecast ($m), 2012-2023

Table 4.10 Global Biologic Therapies Drivers and Restraints, 2012-2023

Table 4.11 Global Corticosteroid Forecast ($m), 2012-2023

Table 4.12 Global Corticosteroids Drivers and Restraints, 2012-2023

Table 4.13 Global Immunomodulators Forecast ($m), 2012-2023

Table 4.14 Global Immunomodulators Drivers and Restraints, 2012-2023

Table 5.1 Global IBD Drug Revenues by Geographical Segments ($m), 2012

Table 5.2 Global IBD Drug Market Forecasts by Country ($m), 2012-2023

Table 5.3 US IBD Drug Market Forecast ($m), 2012-2023

Table 5.4 Japanese IBD Drug Market Forecast ($m), 2012-2023

Table 5.5 EU5 IBD Drug Market Forecasts ($m), 2012-2023

Table 5.6 BRIC IBD Drug Market Forecasts ($m), 2012-2023

Table 5.7 Brazilian IBD Drug Market Forecast ($m), 2012-2023

Table 5.8 Russian IBD Drug Market Forecast ($m), 2012-2023

Table 5.9 Indian IBD Drug Market Forecast ($m), 2012-2023

Table 5.10 Chinese IBD Drug Market Forecast ($m), 2012-2023

List of Tables

www.visiongain.com

Contents Table 6.1 Leading IBD Treatments by Revenue ($m), 2012

Table 6.2 Leading IBD Medicines: Revenue Forecasts ($m), 2012-2023

Table 6.3 World Humira Revenue Forecast ($m), 2012-2023

Table 6.4 Drivers and Restraints for Humira, 2012-2023

Table 6.5 World Remicade Revenue Forecast ($m), 2012-2023

Table 6.6 Drivers and Restraints for Remicade, 2012-2023

Table 6.7 World Asacol Revenue Forecast ($m), 2012-2023

Table 6.8 Drivers and Restraints for Asacol, 2012-2023

Table 6.9 World Pentasa Revenue Forecast ($m), 2012-2023

Table 6.10 Drivers and Restraints for Pentasa, 2012-2023

Table 6.11 World Lialda Revenue Forecast ($m), 2012-2023

Table 6.12 Drivers and Restraints for Lialda, 2012-2023

Table 6.13 World Tysabri Revenue Forecast ($m), 2012-2023

Table 6.14 Drivers and Restraints for Tysabri, 2012-2023

Table 6.15 World Xifaxan Revenue Forecast ($m), 2012-2023

Table 6.16 Drivers and Restraints for Xifaxan, 2012-2023

Table 6.17 World Cimzia Revenue Forecast ($m), 2012-2023

Table 6.18 Drivers and Restraints for Cimzia, 2012-2023

Table 6.19 World Entocort Revenue Forecast ($m), 2012-2023

Table 6.20 Drivers and Restraints for Entocort, 2012-2023

Table 6.21 World Neoral Revenue Forecast ($m), 2012-2023

Table 6.22 Drivers and Restraints for Neoral, 2012-2023

Table 6.23 World Medrol Revenue Forecast ($m), 2012-2023

Table 6.24 Drivers and Restraints for Medrol, 2012-2023

Table 6.25 World Canasa Revenue Forecast ($m), 2012-2023

Table 6.26 Drivers and Restraints for Canasa, 2012-2023

Table 6.27 World Apriso Revenue Forecast ($m), 2012-2023

Table 6.28 Drivers and Restraints for Apriso, 2012-2023

Table 6.29 World Azulfidine Revenue Forecast ($m), 2012-2023

Table 6.30 Drivers and Restraints for Azulfidine, 2012-2023

www.visiongain.com

Contents Table 7.1 Selected IL Inhibitors in Clinical Development, 2013

Table 7.2 Selected CAM Inhibitors in Clinical Development, 2013

Table 7.3 Selected TNF-Alfa Inhibitors in Clinical Development, 2013

Table 7.4 Selected Stem Cell Therapies in Clinical Development, 2013

Table 7.5 Selected Immunomodulators in Clinical Development, 2013

Table 7.6 Selected Chemokine Receptors in Clinical Development, 2013

Table 7.7 Selected Antioxidants and Barrier Function Therapies in Clinical Development, 2013

Table 8.1 SWOT Analysis of the World IBD Drug Market, 2012-2023

Table 8.2 STEP Analysis of the World IBD Drug Market, 2012-2023

Table 9.1 Top 4 Companies for IBD Drugs: Revenues ($m) and Market Shares (%), 2012

Table 9.2 AbbVie Revenues ($m) and Market Share (%), 2012

Table 9.3 Janssen Biotech Revenues ($m) and Market Share (%), 2012

Table 9.4 Warner Chilcott Revenues ($m) and Market Share (%), 2012

Table 9.5 Shire’s Revenues ($m) and Market Share (%), 2012

Table 11.1 Global IBD Revenue Forecasts ($m), CAGR (%) and Market Shares (%) by Product

Category, 2013, 2017, 2023

Table 11.2 Global IBD Revenue Forecasts ($m), CAGR (%) and Market Shares (%) by

Geographical Regions, 2013, 2017, 2023

Table 11.3 Summary of IBD Market Drivers and Restraints, 2013-2023

www.visiongain.com

Contents

Figure 3.1 Treatment Protocol for IBD, 2013

Figure 4.1 World IBD Drugs Market Shares by Product Type (%), 2012

Figure 4.2 Global IBD Drug Market Forecast ($m), 2012-2023

Figure 4.3 World IBD Drugs Market Shares by Product Type (%), 2023

Figure 4.4 Global Aminosalicylates Forecast ($m), 2012-2023

Figure 4.5 Global Antibiotics Forecast ($m), 2012-2023

Figure 4.6 Global Biologic Therapies Forecast ($m), 2012-2023

Figure 4.7 Global Corticosteroid Forecast ($m), 2012-2023

Figure 4.8 Global Immunomodulators Forecast ($m), 2012-2023

Figure 5.1 Global IBD Drug Market by Geographical Segments (%), 2012

Figure 5.2 Global IBD Drug Market by Geographical Segments (%), 2023

Figure 5.3 US IBD Drug Market Forecast ($m), 2012-2023

Figure 5.4 Japanese IBD Drug Market Forecast ($m), 2012-2023

Figure 5.5 EU5 IBD Drug Market Forecasts ($m), 2012-2023

Figure 5.6 BRIC IBD Drug Market Forecasts ($m), 2012-2023

Figure 5.7 Brazilian IBD Drug Market Forecast ($m), 2012-2023

Figure 5.8 Russian IBD Drug Market Forecast ($m), 2012-2023

Figure 5.9 Indian IBD Drug Market Forecast ($m), 2012-2023

Figure 5.10 Chinese IBD Drug Market Forecast ($m), 2012-2023

Figure 6.1 World Humira Revenue Forecast ($m), 2012-2023

Figure 6.2 World Remicade Revenue Forecast ($m), 2012-2023

Figure 6.3 World Asacol Revenue Forecast ($m), 2012-2023

Figure 6.4 World Pentasa Revenue Forecast ($m), 2012-2023

Figure 6.5 World Lialda Revenue Forecast ($m), 2012-2023

Figure 6.6 World Tysabri Revenue Forecast ($m), 2012-2023

Figure 6.7 World Xifaxan Revenue Forecast ($m), 2012-2023

Figure 6.8 World Cimzia Revenue Forecast ($m), 2012-2023

Figure 6.9 World Entocort Revenue Forecast ($m), 2012-2023

List of Figures

www.visiongain.com

Contents Figure 6.10 World Neoral Revenue Forecast ($m), 2012-2023

Figure 6.11 World Medrol Revenue Forecast ($m), 2012-2023

Figure 6.12 World Canasa Revenue Forecast ($m), 2012-2023

Figure 6.13 World Apriso Revenue Forecast ($m), 2012-2023

Figure 6.14 World Azulfidine Revenue Forecast ($m), 2012-2023

Figure 9.1 Top 4 Companies for IBD Drugs: Market Shares (%), 2012

www.visiongain.com

Contents

4SC

Abbott Laboratories

AbbVie

Ablynx

Active Biotech

Aga Khan University Hospital

Ajinomoto Group

Amalyte Pharmaceuticals

Aptalis Pharmaceuticals

ARCA

AstraZeneca

Athersys

Atlantic Pharmaceuticals

Biogen Idec

Bristol-Myers Squibb

Cambridge Antibody Technology

Catabasis Pharmaceuticals

Celgene Cellular Therapies

Celltech Pharmaceuticals

Centocor Ortho Biotech

Centre for Digestive Diseases, Sydney

Centres for Disease Control and Prevention

ChemoCentryx

China Medical

Cosmo Pharmaceuticals

Crohn's and Colitis Foundation of America

Crohn's and Colitis Foundation of Canada

Elan Corporation

Organisations Mentioned in This Report

www.visiongain.com

Contents European Federation of Crohn's and Ulcerative Colitis Associations

European Medicines Agency (EMA)

Food and Drug Administration (US FDA)

Giaconda

Giuliani

GlaxoSmithKline (GSK)

Harbor BioSciences

Hutchison MediPharma

InDex Pharmaceuticals

Isis Pharmaceuticals

Janssen Biotech

Johnson & Johnson

King's College London

Kyorin Pharmaceutical Co.

Lipid Therapeutics

Medarex

Merck & Co.

Mylan Pharmaceuticals

Neovacs

Novartis

Nycomed

Osiris Therapeutics

Otsuka Pharmaceutical Group

Palau Pharma

PDL BioPharma

Pfizer

Probiotic Therapy Research Centre, Sydney, Australia

Procter & Gamble Pharmaceuticals

Prometheus Laboratories

Roche

www.visiongain.com

Contents Salix Pharmaceuticals

Sanofi

Shire Pharmaceuticals Group

Sigmoid Pharma

Takeda

Teva Pharmaceutical Industries

TxCell

UCB

Warner Chilcott

World Gastroenterology Organisation (WGO)

Zealand Pharma

Page 66

www.visiongain.com

Inflammatory Bowel Diseases: World Drug Market 2013-2023

6.5 Lialda (Shire USA) – What Potential for that Medication? Lialda is a new formulation of mesalazine, and is used to treat inflammation in the colon. Like

Asacol, Lialda consists of a pH dependent coating surrounding a core of mesalazine. Lialda's main

selling point is that it is a once-daily formulation, in contrast to most other 5-ASA drugs, which

require several doses throughout the day.

The FDA approved Lialda in the US in 2007. It was released in the UK, as Mezavant, in the same

year, and is now available in most of Europe under this name.

6.5.1 Lialda: Forecast and Analysis, 2013-2023 Lialda has achieved impressive growth since its release in 2007. In 2012, it generated revenues of

$400m worldwide, which represents a 7.53% increase over the 2011 revenue figure 0f $372m.

Visiongain expects this growth to continue, but at a significantly reduced level. By 2017 Lialda will

generate sales of $869m, but by 2023 its revenues will have fallen to $750.9m. The CAGR over

the forecast period was calculated to be 5.23%. Since Lialda’s patent expires in 2020, visiongain

expects it to come under generic competition after this date, and this will cause revenues to begin

contracting.

Lialda has similar efficacy to Asacol but is more convenient to use because of its once daily

dosing. In 2009, Shire presented the results of a 12-month persistency analysis of mesalazine

therapies. Lialda patients were twice as likely to refill their prescription within a set period as

patients on other mesalazine-based drugs, suggesting increased compliance and satisfaction with

the therapy.

Lialda acts on colon, just as Asacol does. However, since it is more convenient to use, it may

replace Asacol as the gold standard treatment for UC. Visiongain predicts that Lialda will erode

Asacol's market share during the forecast period. However, it is worth noting that doctors are

unlikely to switch patients to Lialda from other 5-ASAs that are still generating results for their

patients, and for this reason, Lialda’s growth will be somewhat slower than otherwise expected.

2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023

Lialda Sales ($m) 372.00 400.00 450.80 534.20 652.26 767.05 869.07 954.24 1005.77 1044.99 988.56 890.70 750.86

Annual Growth Rate (%) 7.53 12.70 18.50 22.10 17.60 13.30 9.80 5.40 3.90 -5.40 -9.90 -15.70

CAGR (% from 2013) 17.83 5.23

Table 6.11 World Lialda Revenue Forecast ($m), 2012-2023

Source: visiongain 2013

Page 67

www.visiongain.com

Inflammatory Bowel Diseases: World Drug Market 2013-2023

Drivers Restraints

• Indicated for the induction and

maintenance of remission in UC. The

latter indication will ensure long-term

revenues

• Once daily dosing will improve patient

compliance

• Several years of patent protection

• Will face competition as a maintenance

therapy from the newly approved Apriso

6.6 Tysabri (Elan Pharmaceuticals) - Will Its Side Effects Prove Too

Much? Tysabri is a monoclonal antibody against α4-integrin, an adhesion molecule found on leukocytes

that aids their migration to areas of inflammation. The FDA approved it for treating multiple

sclerosis in 2004, but in February 2005, the drug was voluntarily suspended, based on reports of

adverse events. These reported events concerned three confirmed cases of progressive multifocal

leukoencephalopathy (PML), a rare and often fatal disease of the central nervous system.

0

200

400

600

800

1000

1200

2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023

Sale

s ($

m)

Years

Figure 6.5 World Lialda Revenue Forecast ($m), 2012-2023

Source: visiongain 2013

Table 6.12 Drivers and Restraints for Lialda, 2012-2023

Source: visiongain 2013