Commercial and Pipeline Insight: Inflammatory Bowel Disease - Competition Increases for the Biologics

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