Market Report Source

Overview

Introduction

Research and Development activity in the Hepatitis C arena continue to be high. The market still holds many areas of unmet medical needs: while existing therapies provide good efficacy for about half of the patient population, side effects and limited efficacy in other patients offer much room for improvement. Several development setbacks over the past 18 months highlight the obstacles in R&D.

Scope

In-depth analysis of hepatitis C patient potential and dynamics across the major Western markets Thorough assessment of unmet needs and shortfalls of current HCV therapy Review of current clinical trial practice and key drug classes in development for hepatitis C In-depth discussion of novel hepatitis C pipeline candidates and assessment of their potential in HCV therapy

Highlights

Due to the suboptimal efficacy and safety profile of current standard HCV therapy, there is a large unmet need for drugs with an improved clinical profile. Experts agree that add-on therapy currently seems more promising than interferon or ribavirin replacement approaches. Recent clinical data on small-molecule polymerase and protease inhibitors has sparked high hopes for improving SVR rates through triple therapy. Vertex’s telaprevir, Schering Plough’s boceprevir and Roche’s R-1626 currently show the most promising profiles. Further strategies in HCV drug development include host enzyme inhibitors and non-interferon immunomodulators. However, although theoretically highly promising, most candidates are in very early stages of development and not expected to reach the market soon.

Reasons to Purchase

Review the epidemiological and clinical factors driving new product decisions in hepatitis C as well as unmet needs with current treatment options. Gain insight through a detailed discussion of key pipeline candidates in late-stage development for hepatitis C. Understand where concerns and future opportunities lie by learning about the views of key hepatitis B opinion leaders.

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
Pipeline summary
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
Pipeline summary
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
Pipeline summary
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