炎症性腸疾患

Abstract

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 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