Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the Infectious Diseases pharmaceutical analysis team
- CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the Hepatitis C market
- CHAPTER 2 DISEASE BACKGROUND AND CURRENT TREATMENT
- HCV virology
- Chronic HCV infection silently progresses to liver cirrhosis and cancer
over prolonged periods of time
- Interferon and ribavirin are the standard treatment for HCV
- The current standard of care therapy - Peg-IFN alfa plus ribavirin - has
a suboptimal tolerability and efficacy profile
- Depending on their response to standard therapy, patients can be divided
in different groups
- Key unmet needs include HCV genotype 1 infection, non-response to
current therapy and improved drug tolerability
- CHAPTER 3 PATIENT POTENTIAL
- HCV is a major health concern with 180 million people infected globally
- Intravenous drug users and people who received blood transfusions before
1990 are at highest risk of infection
- The number of CHC patients seeking treatment is expected to peak within
the next 10-20 years
- Across the 7MM, immigration from high prevalence countries influences
overall prevalence rates for HCV
- HCV genotype 1, which is particularly hard to treat, accounts for the
majority of infections in the 7MM
- The prevalence of genotypes varies by country
- Whereas SVR rates are high for genotypes 2 and 3, genotypes 1 and 4
are much harder to treat
- Patients with an African background show poorer treatment outcomes if
they suffer from genotype 1
- The treatment of HIV/HCV co-infected patients is particularly challenging
- There are few treatment options for the large population of
non-responders and relapsers
- The high incidence of post-transplant HCV re-infection has created an
important niche market
- CHAPTER 4 R&D APPROACH
- Of the drug classes are in development for HCV, small molecule
antivirals show best prospects
- Multiple different drug classes are being developed for use in HCV
- ' Add-on' therapy to current standard treatment is the most promising
approach in HCV drug development
- Developmental drug strategies
- Due to the late characterization of the hepatitis C virus, drug
development has been slow
- Future HCV therapy is likely to involve combinations of at least three
drugs
- Current clinical trials focus on achieving higher SVR rates in
genotype-1 patients and non-responders
- In late-stage trials, comparison with peginterferon/ribavirin is a
must for new drug candidates
- Trials are mostly conducted in genotype-1 patients
- The achievement of a sustained virological response (SVR) is the key
endpoint in both HCV clinical trials and therapy
- CHAPTER 5 INTERFERONS
- Interferons have a non-specific, broad antiviral activity
- The mechanism of Interferon alfa against HCV infection has not been
elucidated
- Standard interferons were first in class but have poor efficacy as
monotherapy
- Pegylated interferons in combination with ribavirin have become
established as standard therapy
- Pipeline efforts concentrate on long-acting formulations of interferon
alfa with better tolerability
- Pipeline summary
- Albuferon (Human Genome Sciences/Novartis) - threatening the leading
position of the peginterferons
- Profile
- Key clinical trials
- Datamonitor analysis
- IFNalpha-2b XL (Flamel Technologies) - more results needed to confirm
positive top-line data
- Profile
- Key clinical trials
- Datamonitor analysis
- Locteron (OctoPlus/Biolex Therapeutics) - high EVR rates and good
safety profile raise high hopes
- Profile
- Key clinical trials
- Datamonitor analysis
- Omega Interferon (Intarcia) - potential only lies in sustained release
formulation
- CHAPTER 6 SMALL MOLECULE ANTIVIRALS
- Due to the insufficient efficacy of current HCV therapy, targeted
antivirals are a popular approach for new HCV therapies
- HCV NS5B polymerase inhibitors - R-1626 leading the way following
late-stage pipeline failures
- Rationale for HCV NS5B polymerase inhibitors
- Inhibition of the NS5B polymerase specifically blocks HCV
replication at an early stage
- Nucleoside and non-nucleoside inhibitors block polymerase activity
by different mechanisms
- Pipeline overview
- R-1626 (Roche) - positive interim Phase II results sparking high hopes
- Profile
- Key clinical trials
- Datamonitor analysis
- Other HCV polymerase inhibitors - Gilead and Roche are benefiting from
Novartis' s and Wyeth' s trial failures
- GS-9190 (Gilead) - Phase I trial demonstrates antiviral activity and
good pharmacokinetics
- R-7128 (Roche/Pharmasset) - trials evaluating combination with
standard therapy in progress following positive Phase I results
- NS3/4A protease inhibitors - Telaprevir facing challenges
- Rationale for HCV NS3/4A protease inhibitors
- The NS3 protease is essential for viral replication
- The HCV protease as a drug target: ideal in theory, difficult in
practice
- Combination therapy with pegylated interferons and/or other
antivirals will be the preferred regimen for protease inhibitors to
control resistances
- Pipeline overview
- VX-950 (telaprevir; Vertex) - handicapped by dosing and resistances
- Profile
- Key clinical trial overview
- Datamonitor analysis
- SCH 503034 (boceprevir; Schering-Plough) - emerging as competitor for
VX-950
- Product overview
- Key clinical trial overview
- Datamonitor analysis
- Other HCV protease inhibitors - two promising newcomers in Phase I
- TMC435350 (Medivir/Johnson & Johnson)
- ITMN-191 (Roche/InterMune)
- Other small molecule antivirals - uncertain future for taribavirin
- Pipeline overview
- Taribavirin (Viramidine; Valeant Pharmaceuticals) - Phase IIb results
will determine fate of the drug following VISER-1 and VISER-2 failures
- Profile
- Key clinical trials
- Datamonitor assessment
- KPE02003002 (Kemin Pharma) - no updates since 2004
- CHAPTER 7 IMMUNOMODULATORS (NON-INTERFERON)
- Immunomodulators are mostly developed as add-ons to existing therapy,
using HCV as a secondary indication
- Product profiles - best outlook for civacir
- Zadaxin (SciClone)
- Civacir (Nabi Biopharmaceuticals/Kedrion)
- IM-862 (Implicit Bioscience)
- IPH 1101 (Innate Pharma)
- KRN-7000 (Kirin)
- SCV-07
- Therapeutic vaccines - a long way to go
- IC-41 (Intercell AG) - more long-term data needed
- Profile
- Key clinical trial overview
- Datamonitor analysis
- HCV vaccine (Novartis/CSL) - no progress reported since 2004
- CHAPTER 8 HOST ENZYME INHIBITORS
- The main role for host-enzyme inhibitors will be as add-on to standard
therapy rather than as monotherapy
- Product profiles - Most candidates are still in early stages
- Celgosivir (Migenix)
- Profile
- Key clinical trials
- Datamonitor assessment
- NIM-811 (Novartis)
- Debio-025 (Debiopharm)
- VGX-410C (mifepristone; VGX Pharmaceuticals)
- Alinia (nitazoxanide; Romark Laboratories)
- APPENDIX A
- Bibliography
- Report methodology
- APPENDIX B
- About Datamonitor
- About Datamonitor Healthcare
- Datamonitor Healthcare' s therapy area capabilities
- About the Infectious Diseases analysis team
- Key therapy team members
- Holger Rovini, Head of Respiratory and Infectious Diseases
- Hedwig Kresse, Analyst, Infectious Diseases
- Disclaimer
- List of Tables
- Table 1: Interferons and ribavirin are the only marketed HCV
antivirals, 2007
- Table 2: HIV mono-infected and HIV/HCV co-infected populations, 7MM,
2007
- Table 3: Key trials for therapy in nonresponders to previous treatment
with peginterferon / ribavirin
- Table 4: Mode of action of developmental immunomodulators (non-IFN),
2007
- Table 5: Mode of action of developmental interferons, 2007
- Table 6: Mode of action of developmental small molecule antivirals,
2007
- Table 7: Mode of action of developmental host enzyme inhibitors, 2007
- Table 8: Key endpoints used in clinical trial design for HCV
- Table 9: HCV pipeline overview - late-stage interferons, 2007
- Table 10: Albuferon - ACHIEVE 1 trial design
- Table 11: Albuferon - ACHIEVE 2/3 trial design
- Table 12: Albuferon - Phase IIb (treatment-naïve) trial design and
results
- Table 13: Albuferon - Phase II (nonresponder) trial design and results
- Table 14: Locteron - Phase IIa clinical trial design and results
- Table 15: HCV pipeline overview -- late-stage small molecule
antivirals, 2007
- Table 16: HCV pipeline overview - NS5B polymerase inhibitors, 2007
- Table 17: R-1626 - Phase IIa clinical trial overview and interim
results
- Table 18: R-1626 - Phase IIb clinical trial overview and interim
results
- Table 19: HCV pipeline overview - NS3/4A protease inhibitors, 2007
- Table 20: Telaprevir -PROVE 1 study design and interim results
- Table 21: Telaprevir - PROVE 2 study design and interim results
- Table 22: Telaprevir - PROVE 3 study design
- Table 23: Boceprevir - SPRINT-1 study design and preliminary results
- Table 24: Boceprevir - Phase II study design and preliminary results
- Table 25: HCV pipeline overview - late-stage other antivirals, 2007
- Table 26: Taribavirin - VISER-1 Phase III study design and results
- Table 27: Taribavirin - VISER-2 Phase III study design and results
- Table 28: Taribavirin - Phase IIb trial design
- Table 29: HCV pipeline overview - immunomodulators (non-IFN), 2007
- Table 30: HCV pipeline - late-stage therapeutic vaccines, 2007
- Table 31: IC-41 - Phase II monotherapy trial overview and interim
results
- Table 32: IC-41 - Phase II combination trial overview and interim
results
- Table 33: HCV pipeline - late-stage host enzyme inhibitors, 2007
- Table 34: Celgosivir - Phase II combination trial design and results
- List of Figures
- Figure 1: HCV - genome organisation
- Figure 2: HCV - course of disease
- Figure 3: Efficacy of Pegasys + Copegus by HCV genotype
- Figure 4: HCV - patient classification by response to treatment
- Figure 5: HCV - key unmet needs
- Figure 6: HCV diagnosis, 7MM, 2004
- Figure 7: HCV - global disease prevalence and infection numbers
- Figure 8: HCV prevalence and potential patient population across the
7MM, 2007
- Figure 9: Sources of infection for HCV patients; US, 2006
- Figure 10: HCV genotype split by country; Europe, US and Japan, 2007
- Figure 11: Late-stage HCV drug pipeline (Phase II and III) by class,
December 2007
- Figure 12: Strategies for HCV drug development
- Figure 13: The HCV NS3-encoded serine protease cleaves the
non-structural HCV proteins
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