Market Report Source

Overview

Introduction

Ulcerative colitis and Crohn’s disease are the primary constituents of Inflammatory Bowel Disease, which is estimated to affect approximately 1.8 million people in the seven major markets. Eight years after the launch of Remicade in Crohn’s disease the next generation of anti-TNF’s are poised for approval, but the anti-TNF class will soon be under attack from novel cytokine therapies.

Scope

*Ulcerative colitis and Crohn’s disease ten-year forecasts, contrasted against estimated total brand sales *Sales and volume estimates by indication from 2005-2015 for the US, combined five major EU markets (France, Germany, Italy, Spain, UK) and Japan *Analysis of late-stage pipeline products for Crohn’s disease and ulcerative colitis *Discussion of future events that affect the sales and volume of key brands

Highlights

The battle between Cimzia and Humira will depend on efficacy, convenience and cost. Datamonitor believes Humira’s efficacy in all patient segments, including low CRP patients and it’s wealth of safety data, added to the fact that it has already been used off-label, will win out over Cimzia superior dosing regime.

Patient segmentation is expected to be crucial in the future of IBD treatment. The maintenance of clinical remission and mucosal healing should be considered key outcomes, which should be targeted towards specific groups to aid product differentiation.

Ulcerative colitis patients respond better than Crohn’s patients to 5-ASAs and surgery, which can effectively be a cure, therefore Datamonitor predicts less success for the biologics in ulcerative colitis. Companies should be aware that IBD is estimated to be neither the most prevalent or profitable indication for autoimmune biologics.

Reasons to Purchase

*Compare inflammatory bowel disease forecasts with total brand sales for key existing products *Estimate the size of the Crohn’s disease and ulcerative colitis markets to 2015 *Benchmark late-stage pipeline products against the market leader

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Inflammation and Immune Disorders pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Objective of the analysis

Datamonitor insight into the IBD market

CHAPTER 2 EPIDEMIOLOGY AND PATIENT NUMBERS

Definition and diagnosis

Patient segmentation in the Inflammatory Bowel Disease spectrum

Prevalence and incidence of Inflammatory Bowel Disease

Crohn’s disease

Ulcerative colitis

Overview of Inflammatory Bowel Disease epidemiology studies

US

Europe

Japan

Ulcerative colitis incidence stabilizes as Crohn’s disease continues to rise

Reduction in North-South prevalence divide

NOD2 genetic connection

CHAPTER 3 MARKET DEFINITION AND OVERVIEW

Current market players

Centocor and Procter and Gamble’s blockbuster products lead, but Salix’s diversity and UCB’s pipeline are significant

Current treatment classes

Anti-inflammation drugs

Corticosteriods

Traditional immunosuppressants

Biologic targeted immunosuppression

Antibiotics

Anti-diarrheal and fluid replacements

ICD-10 codes used to define the IBD indications

Ulcerative colitis ICD-10 definition

Crohn’s disease ICD-10 definition

Treatment algorithm

Ulcerative colitis does differ in treatment from Crohn’s disease

5-ASAs tend to be more effective in ulcerative colitis

Crohn’s disease is treated with a wider range of drugs as surgery is not always effective

Step-up versus top-down

Unmet needs and challenges in Inflammatory Bowel Disease

How many rescue therapies can patients use?

Patient compliance an issue for 5-ASAs

Maintenance of remission and mucosal healing need to be proven

Standardized ulcerative colitis endpoints

Immunogenicity of biologic products

CHAPTER 4 COMMERCIAL FORECAST ANALYSIS

Remicade approval in ulcerative colitis

Remicade is first to market in ulcerative colitis for induction AND maintenance of remission

EMEA approves Remicade in EU to treat ulcerative colitis

Remicade boosted by prompt approval for maintenance of remission in ulcerative colitis in the US and EU

Additional anti-TNF brand launches

The biologic battle begins

Cimzia predicted to launch first in the US, but Humira likely to beat Cimzia to the European market

Centocor, Schering-Plough and Tanabe continue to roll out the approvals

Approval of Remicade for children with active Crohn’s disease in US and EU

Remicade approved for maintenance of remission in Crohn’s disease in Japan

Remicade approved as second-line therapy in Crohn’s disease in the EU

NICE review of Remicade, Cimzia and Tysabri

Launch of 5-ASAs reformulations and new delivery technologies

Reformulations dominate the 5-ASAs

Pentasa increases US price in January 2006

Salix invests in Colazal development

Retail corticosteroids

Entocort EC is the leading retail corticosteroid

Entocort EC (budesonide) capsules recommended by the American Gastroenterology Association as first-line therapy for the treatment of mild to moderate Crohn’s Disease

Warnings and safety issues

Immunosuppression can be a dangerous treatment path

Health Canada warn about cancer links in children and adolescents treated with Remicade

Hepatitis B reactivation warning for all anti-TNF agents in Canada

Patent expiries

Impact of patent expiries increases as cost containment becomes a global issue

US is trying to catch up with the EU in the biosimilars’ race

Colazal patent expiry

Data definitions, limitations and assumptions

Standard units

Japanese market data

Derivation of sales forecasts and pricing trends

Inflammatory Bowel Disease indication breakdown

Diagnosis value based on retail data only

CHAPTER 5 LATE-STAGE PIPELINE ANALYSIS

Key classes in the pipeline

Anti-TNF

Cytokine

Mesalazine

Regional launch dates and prices for new products

Humira (adalimumab)

Forecast and assumptions

Historical delay between submission and approval used to predict launch date

Patient and marketing potential

Humira rapidly achieves multiple indications

Humira is well positioned for use in Remicade failures, estimated at 60% after a year

Approval in ulcerative colitis expected to follow

Overview of latest Humira clinical trials

Cimzia (certolizumab pegol)

Forecast and assumptions

Strong uptake expected but competition reduces potential

Cost advantage hangs in the balance

Market and patient potential

Patient friendly injector may come too late as the competition beats UCB to it

Priority backing and Inflammatory Bowel Disease support by UCB essential for Cimzia to finally reach the market

Poor response in low CRP patients casts a shadow over trial results

Overview of latest Cimzia clinical trials

Nuvion (visilizumab)

Forecast and assumptions

Uptake limited to steroid-refractory ulcerative colitis patients

Patient and marketing potential

Fast Track status will help but cytokine release syndrome and Epstein-Barr virus side effects reduce patient potential

Clinical trial overview

Ulcerative colitis

Crohn’s disease

Tysabri (natalizumab)

Forecast and assumptions

Approval in Crohn’s disease forecast following MS approval but uptake will be limited by TOUCH program

High cost may recoup some revenue but sales in MS are more likely to provide the return on investment

Patient and marketing potential

PML risk and poor response in low CRP patients limits use to after anti-TNF therapy

Clinical trial overview

Prograf/Protopic (tacrolimus)

Forecast and assumptions

Prograf listed in pipeline for UC in Japan, and expansion into other markets is not expected

Patient and marketing potential

Clinical trial overview

Leukine/Prokine (sargramostim)

Forecast and assumptions

Patient and marketing potential

Multiple studies are planned but recruitment may be an issue here

Studies show some efficacy but the use of the higher CDAI 100 as an endpoint should be taken into account

Clinical trial overview

Mesavance (mesalazine MMX)

Forecast and assumptions

Off-label use is also predicted on the launch of Mesavance as is seen in all other 5-ASA products

Patient and marketing potential

A once-daily formulation meets a high unmet need but the physical size of the tablet may cause an issue with patients

Shire also markets Pentasa in the US and the launch of Mesavance will create conflict, although Pentasa’s high proportion of sales from off-label CD indications may save it

Clinical trial overview

Tetomilast (OPC-6535)

Forecast and assumptions

Tetomilast is expected to be used as an alternative to 5-ASAs but uptake will depend on results of more efficacy data

Patient and marketing potential

Pre-clinical and early phase results are promising but more side-effect data are essential

Clinical trial overview

Colal-Pred (prednisolone sodium metasulfobenzoate)

Forecast and assumptions

Patient and marketing potential

Clinical trial overview

ABT-874

Forecast and assumptions

Patient and marketing potential

Clinical trial overview

Other Inflammatory Bowel Disease pipeline agents

Salofalk Granu-Stix

Alicaforsen (ISIS-2302)

Golimumab (CNTO-148)

CNT0-1275

Colirest (CBP-1011)

Gastrom enema formulation (ecabet/TA-2711E)

MLN02

TC-2401

Nicotine

HuZaf (fontolizumab)

Apilimod (STA-5326)

Traficet-EN (CCX-282)

RDP-58

Teduglutide

Recently discontinued projects

Apaza (NAA-004)

APPENDIX A – MARKET DATA AND MAJOR BRAND KEY FACTS

Summary Inflammatory Bowel Disease market data

Pricing calculations and assumptions

Biologic key brands

Immunosuppressant key brands

Intestinal anti-inflammatory key brands

Corticosteroids key brands (retail only)

APPENDIX B – MARKET FORECAST DATA

US forecast data

EU forecast data

Japan forecast data

APPENDIX C- BIBLOGRAPHY AND METHODOLOGY

Report methodology

Forecast methodology

About Datamonitor

About Datamonitor Healthcare

About the IDI analysis team

Disclaimer

List of Tables

Table 1: Prevalence and incidence of Crohn’s disease in the seven major markets by country, 2006

Table 2: Prevalence and incidence of ulcerative colitis in the seven major markets by country, 2006

Table 3: Epidemiology studies into incidence and prevalence of IBD, 1984-2002

Table 4: Incidence of IBD in the European over-15 population, October 1991-September 1993

Table 5: Prevalence studies for IBD in Europe

Table 6: Estimated prevalence and incidence of Crohn’s disease in Japan, 1986-1998

Table 7: Key players in IBD in the seven major markets, 2006

Table 8: Remicade ACT 1&2 trial results (Patient % achieving response, remission and mucosal healing)

Table 9: Cimzia and Humira forecast launch dates

Table 10: Remicade’s pediatric Crohn’s disease results

Table 11: Late-Phase IBD pipeline products, 2006

Table 12: Phase I and II IBD pipeline, 2006

Table 13: Estimated launch dates across the US, EU and Japan for late-phase pipeline IBD products, 2006

Table 14: Benchmark brand $ per SU values, 2005

Table 15: Formulary price comparison between regions for biologic products, 2006

Table 16: Humira past and forecast time delay between submission and approval for the FDA and EMEA, 2002-06

Table 17: Tacrolimus studies in refractory IBD, 1998-2006

Table 18: Brands currently approved in IBD for sulfasalazine and its derivatives, 2006

Table 19: Abstracts and posters presented at key GI conferences in 2006 for mesavance

Table 20: Estimated Crohn’s disease sales in seven major markets, by class

Table 21: Estimated ulcerative colitis sales in seven major markets, by class

Table 22: Intestinal anti-inflammatory dollar per standard unit assumptions, 2005

Table 23: Remicade: key facts

Table 24: Humira: key facts

Table 25: Neoral: key facts

Table 26: Salazopyrin: key facts

Table 27: Asacol: key facts

Table 28: Pentasa: key facts

Table 29: Colazal: key facts

Table 30: Dipentum: key facts

Table 31: Entocort: key facts

Table 32: US forecast sales data, $m, 2005-2015

Table 33: Five major EU markets sales forecast, $m, 2005-2015

Table 34: Japanese sales forecast, $m, 2005-2015

List of Figures

Figure 1: Ulcerative colitis and Crohn’s disease in the digestive tract

Figure 2: Trends in Crohn’s disease incidence over time and by age group, 1940-1993

Figure 3: Sales of top five marketed IBD products in the seven major markets ($m), 2002-05

Figure 4: Gastroenterology brands marketed by Salix, 2006

Figure 5: IBD overview treatment algorithm

Figure 6: Step-up versus top-down approach

Figure 7: Sustained response and remission in ulcerative colitis for both weeks 8 and 30, ACT 1 & 2 trial data

Figure 8: Remicade uptake in IBD in the US and 5EU, 2002-2015

Figure 9: Comparative advantages and disadvantages of Humira and Cimzia

Figure 10: Remicade global* sales, split by IBD and other indications, 2005-2015

Figure 11: Tanabe’s expectations for Remicade approvals in Japan

Figure 12: Estimated percentage use of Remicade in Japan by indication, 2006

Figure 13: Pentasa sales value and volume ($m and SU), 2002-2015

Figure 14: Entocort US forecast ($m), 2006-2015

Figure 15: Estimated sales breakdown by indication for key US brands, 2005

Figure 16: EU key brands with estimated sales breakdown by indication, 2005

Figure 17: Breakdown of clinical trial pipeline for IBD agents, 2006

Figure 18: Working hypothesis regarding the role of cytokines in the pathogenesis of Crohn’s disease

Figure 19: Humira commercial and clinical scores

Figure 20: Humira’s forecast for Crohn’s disease and total brand sales in the seven major markets ($), 2002-2015

Figure 21: Cimzia commercial and clinical scores

Figure 22: Cimzia global (7MM) Crohn’s disease forecast, 2006-2015

Figure 23: Nuvion commercial and clinical scores

Figure 24: Nuvion global (7MM) forecast in ulcerative colitis

Figure 25: Tysabri commercial and clinical scores

Figure 26: Tysabri global Crohn’s disease sales forecast, 2005-2015

Figure 27: Tysabri ENACT-1 and 2 results

Figure 28: Prograf commercial and clinical scores

Figure 29: Leukine commercial and clinical scores

Figure 30: Mesavance commercial and clinical scores

Figure 31: Mesavance global sales forecast, 2005-2015

Figure 32: Mesavance results from two combined Phase III clinical trials in moderate to severe ulcerative colitis

Figure 33: Tetomilast commercial and clinical scores

Figure 34: Colal-Pred commercial and clinical scores

Figure 35: Colal-Pred ulcerative colitis sales, 2005-2015