Table of Contents

Pipeline and Commercial Insight: Hepatitis C - High unmet need drives rapid innovation - A comprehensive overview and in-depth assessment of drugs in the Hepatitis C pipeline, assessing their clinical relevance and revenue potential. The report also explores key issues in the HCV market, from patient potential to clinical trial design.

Product Code: dmhc2454

Publication Date: 18-Dec-2008

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Overview

Introduction

The Hepatitis C market was worth $2.3 billion in 2007, declining at a CAGR of -2.8% from 2004-2007. Despite this recent slump, Datamonitor forecasts sales to grow to $4.5 billion by 2017, driven primarily by the launch of the new protease inhibitors. The US and EU will remain the largest markets, generating $1.9 billion and $1.7 billion respectively in 2017.

Scope

· An overview of the current Hepatitis C market and its key players

· In-depth analysis of Phase II and III clinical development compounds and comprehensive overview of Phase I drugs

· Epidemiological dynamics of Hepatitis C in the six major markets are discussed along with unmet needs

· 10 year sales forecasts for marketed and six pipeline drugs

Highlights

Given its large patient potential and significant unmet needs, the Hepatitis C market has attracted considerable interest from companies with a strong presence in infectious diseases. The HCV pipeline is therefore very active and consists of drugs with various mechanisms of action.

Several strategies are being explored in clinical trials, including add-on therapy to the current standard of care, interferon replacement and ribavirin replacement. Of these Datamonitor believes that add-on therapy will be the most successful in the medium term.

The two most advanced pipeline candidates are Schering Plough's boceprevir and Vertex's telaprevir. Both drugs have demonstrated comparable efficacy benefits when combined with current standard of care. Datamonitor expects telaprevir to gain higher market share due to its ability to cut short the overall duration of therapy in genotype 1 patients.

Reasons to Purchase

· Understand current and future Hepatitis C market dynamics

· Gain insight into the unmet needs of HCV patients and the extent to which pipeline drugs are addressing these issues

· Evaluate the Hepatitis C market forecast for existing and key pipeline drugs to 2018

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ABOUT DATAMONITOR HEALTHCARE	2
About the Infectious Diseases and Respiratory pharmaceutical analysis team	2
CHAPTER 1 EXECUTIVE SUMMARY	3
Datamonitor insight into the hepatitis C market	3
Key metrics	6
Datamonitor Pipeline Assessment Summary	8
Contributing experts	9
Related reports	9
CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS	11
Current market overview	11
Pegylated interferon alpha in combination with ribavirin is current standard of care	12
The history of hepatitis C virus therapy from interferon monotherapy to pegylated interferon plus ribavirin combination therapy	13
Standard interferon monotherapy was initially used to treat hepatitis C virus	13
Ribavirin enhances the effects of interferons but is associated with anemia	15
Pegylation of standard interferon reduced the dosing frequency	16
The hepatitis C pipeline is highly active	17
The hepatitis C virus pipeline consists of compounds with different mechanisms of action	19
Datamonitor expects the hepatitis C virus market to increase to $4.5 billion by 2017	23
Key companies involved in the hepatitis C virus pipeline	25
Roche	26
Schering Plough	28
Vertex	29
CHAPTER 3 DISEASE OVERVIEW - PATIENT POTENTIAL	31
Definition of hepatitis C virus	31
Hepatitis C virus escapes immune surveillance by the host, causing chronic infection	31
Chronic hepatitis C virus infection silently progresses to liver cirrhosis and cancer over prolonged periods of time	32
Significantly higher hepatitis C virus prevalence is found in intravenous drug users and patients who received blood transfusions before the 1990s	34
Immigration from areas of high prevalence is having a growing impact	35
The number of patients developing chronic hepatitis C will increase over the coming years	36
Management of hepatitis C virus	36
Segmentation of hepatitis C virus	37
Patients can be stratified according to hepatitis C virus genotype	37
The distribution of hepatitis C virus genotypes varies by geography and route of transmission	38
Genotype 1 is the most difficult to treat	40
There are different types of response to therapy	40
Epidemiology of hepatitis C virus	41
Estimating prevalence	42
US	42
Japan	43
Europe	44
France	45
Germany	45
Italy	45
Spain	46
UK	46
The HCV market has significant unmet needs	46
High efficacy in genotype 1 patients and non-responders remains the greatest unmet need	47
Improvements in tolerability and dosing may lead to better treatment outcomes	48
Shortened duration of treatment	49
Drugs efficacious in patients who do not respond or show intolerance to interferon	50
Effective therapies for hepatitis C patients of non-Caucasian ethnicity (African-American, Asian)	51
Drugs efficacious in HCV/HIV co-infection	51
CHAPTER 4 R&D APPROACH	53
Classification of pipeline products	53
Interferons	53
Small molecule antivirals	54
Immunomodulators	54
Therapeutic vaccines	54
Clinical trial design in hepatitis C virus	55
Future hepatitis C virus therapy falls into three distinct categories	55
Add on therapy currently appears to be the most promising strategy	55
Interferon and ribavirin replacement is unlikely	55
Sustained virological response is the most frequently used endpoint	57
Early virological response and rapid virological response are strong predictors of sustained virological response and are increasingly being used	58
Patients are stratified according to genotype and response to therapy	59
Clinical trials for novel agents are focusing on genotype 1 patients	59
The non-responder population is also attractive given the high unmet need	60
Late-stage trials involve comparison with current standard of care	60
Reducing the duration of treatment	61
Implications of new drug launches on clinical trial design	61
CHAPTER 5 INTERFERONS LATE-STAGE DRUG ANALYSIS & FORECASTS	63
Overview of the interferon class	63
Pipeline summary	65
Comparative forecasts	66
Pegylated interferon (peginterferon) combined with ribavirin is the current gold standard	66
Peginterferon therapy is associated with a high incidence of side effects and limited efficacy in genotype 1 patients	69
Albuferon (Novartis/Human Genome Sciences)	69
Drug overview	69
Clinical trial data	70
Phase III studies	70
Phase IIb studies	71
Phase II studies	73
Marketing factors	73
Patient potential	74
Satisfaction of unmet needs	75
Forecasts to 2017	75
Locteron (Biolex)	76
Drug overview	76
Clinical trial data	77
Phase IIb - SELECT 2 trial	77
Phase IIa - SELECT-1 trial	77
Phase IIa - PLUS trial	78
Marketing factors	78
Patient potential	79
Satisfaction of unmet needs	79
Forecasts to 2017	79
IFNalpha-2b XL (Flamel Technologies)	80
Drug overview	80
Clinical trial data	80
Phase II studies	80
Datamonitor comments	82
Other drugs in the interferons class	82
Omega-interferon (Intarcia)	82
CHAPTER 6 SMALL MOLECULE ANTIVIRALS LATE-STAGE DRUG ANALYSIS AND FORECASTS	84
Overview for the small molecule antivirals class	84
Resistance to new hepatitis C virus antivirals is an emerging issue	85
Pipeline summary	87
Comparative forecasts	91
Hepatitis C virus NS5B polymerase inhibitors	93
Pipeline overview	93
R7128 (Roche and Pharmasset)	96
Drug overview	96
Key clinical trials	96
Datamonitor comments	99
Forecasts to 2017	99
GS-9190 (Gilead)	100
VCH-916	101
PF-868554	102
Hepatitis C virus NS3/4A protease inhibitors	102
Pipeline overview	103
Telaprevir (Vertex and Tibotec)	106
Drug overview	106
Key clinical trials	106
Marketing factors	113
Patient potential	113
Satisfaction of unmet needs	113
Forecasts to 2017	114
Boceprevir	115
Drug overview	115
Key clinical trials	115
Marketing factors	120
Patient potential	120
Satisfaction of unmet needs	121
Forecasts to 2017	123
Protease inhibitors in early stage development	124
TMC435350 (Tibotec/Johnson & Johnson)	124
Key clinical trials	124
Datamonitor comments	125
R7227/ITMN-191 (Roche and InterMune)	126
Key clinical trials	126
Datamonitor comments	127
BI 201335	127
Other small molecule antivirals	128
Pipeline overview	128
Taribavirin (Valeant Pharmaceuticals)	130
Key clinical trials	130
Datamonitor comments	134
Forecasts to 2017	135
BMS-790052 (Bristol Myers Squibb)	135
CHAPTER 7 IMMUNOMODULATORS (NON-INTERFERON) LATE-STAGE DRUG ANALYSIS	137
Pipeline overview	137
Product profiles	139
Zadaxin (SciClone Pharmaceuticals)	139
SCV-07 (SciClone Pharmaceuticals)	139
Bavituximab (Peregrine Pharmaceuticals)	140
Civacir (Nabi Biopharmaceuticals)	140
Alinia (Romark Laboratories)	141
IPH 1101 (Innate Pharma)	141
CYT 107 (Cytheris)	142
CHAPTER 8 THERAPEUTIC VACCINES LATE STAGE DRUG ANALYSIS	143
Overview for the therapeutic vaccines class	143
Pipeline overview	144
IC41 (Intercell and Novartis)	146
Key clinical trial data	146
Phase II monotherapy study	146
Phase II combination study	147
Datamonitor comments	147
GI-5005 (GlobeImmune)	147
Drug overview	147
Key clinical trials	148
Phase II	148
Phase Ib	148
Datamonitor comments	149
ChronVac-C (Tripep and Inovio)	149
Drug overview	149
CHAPTER 9 HOST ENZYME INHIBITORS	151
Pipeline overview	151
Celgosivir (MX-3253; Migenix)	153
Debio-025 (Debiopharm)	154
NIM-811 (Novartis)	154
BIBLIOGRAPHY	155
Journals	155
Websites	157
Others	160
Datamonitor reports	164
APPENDIX	165
Methodology	165
Product forecasts	165
Definition of a standard unit (only use if ForeSight model used to forecast)	166
Forecasts for new drug classes (telaprevir, boceprevir, R-7128)	166
Pricing assumptions	166
Calculation of volume	168
Contributing experts	172
About Datamonitor	173
About Datamonitor Healthcare	173
Datamonitor Healthcare's therapy area capabilities	174
About the Disease analysis team	174
Key therapy team members	176
Holger Rovini, Lead Analyst, Infectious Diseases and Respiratory	176
Disclaimer	177
List of Tables
Table 1: Key parameters of HCV for the seven major markets	6
Table 2: Forecast key pipeline products in HCV in 2017 ($m)	7
Table 3: Overview of products in Phase I-III development	20
Table 4: Overview of hepatitis C virus pipeline drugs included in Datamonitor's forecasts, 2008	22
Table 5: Prevalence of Hepatitis C in Spain	46
Table 6: Estimated number of HIV/HCV co-infected patients by country in the seven major markets, 2008	52
Table 7: Overview of classes in development for hepatitis C virus, 2008	53
Table 8: Hepatitis C virus pipeline overview for the interferon class, 2008	64
Table 9: Overview of the result from the IDEAL study	68
Table 10: Resistant mutations associated with virus inhibitors	86
Table 11: Overview of small molecule antivirals in development	88
Table 12: Hepatitis C virus pipeline overview - NS5B polymerase inhibitors, 20072008	94
Table 13: Hepatitis C virus pipeline overview - NS3/4A protease inhibitors, 20072008	104
Table 14: PROVE-1 response rates for Telaprevir in hepatitis C virus	108
Table 15: PROVE-2 final analysis for Telaprevir in hepatitis C virus	110
Table 16: SVR12 rates for telaprevir-based 24 week regimen (group 1) in hepatitis C virus	111
Table 17: Interim results from the C208 study for Telaprevir in hepatitis C virus	112
Table 18: Adverse event-related discontinuations and virological breakthroughs by treatment arm for Telaprevir in hepatitis C virus in the C208 study	112
Table 19: Sustained virological response rates from SPRINT-1 study by treatment arm for boceprevir in hepatitis C virus	119
Table 20: Comparison of boceprevir and telaprevir SVR rates	122
Table 21: Hepatitis C virus pipeline overview -other small molecule antivirals, 20072008	129
Table 22: Taribavirin Phase IIb efficacy and safety data in hepatitis C virus	134
Table 23: Hepatitis C virus pipeline overview - immunomodulators (non-interferon), 20072008	138
Table 24: Hepatitis C virus pipeline overview - therapeutic vaccines, 2007	145
Table 25: HCV pipeline overview - host enzyme inhibitors, 2008	152
Table 26: Diagnostic split for US interferon and ribavirin sales	165
Table 27: Datamonitor drug assessment parameters	171
List of Figures
Figure 1: Datamonitor drug assessment summary of therapies in late stage development for HCV, 2008	8
Figure 2: Hepatitis C virus sales by region in the US, Japan and the 5EU, 2004-07	12
Figure 3: Evolution of chronic HCV therapy in the US since the launch of Intron A in 1991	14
Figure 4: Improvement in sustained virological response rates from monotherapy to combination therapy	17
Figure 5: Hepatitis C pipeline overview by drug class and phase, 2008	18
Figure 6: HCV pipeline overview	18
Figure 7: Estimated US launch dates of forecasted pipeline drugs for hepatitis C virus, 2008	23
Figure 8: HCV sales 2007-2017 by region	24
Figure 9: HCV sales or marketed drugs versus new drugs 2007-2017	25
Figure 10: Interferon sales 2003-2007	26
Figure 11: Interferons class share from 2003 to 2007	27
Figure 12: Interferon and ribavirin sales 2004-2007	28
Figure 13: The hepatitis C virus genome	32
Figure 14: Hepatitis C virus disease progression	33
Figure 15: Genotype distribution of hepatitis C virus across Europe, 2007	39
Figure 16: Hepatitis C virus - patient classification by response to treatment	41
Figure 17: Incidence of hepatitis C virus in the US, 1982-2006	43
Figure 18: Age-specific prevalence of anti-HCV antibodies in first-time blood donors in eight districts of Japan	44
Figure 19: Unmet needs in hepatitis C virus, 2008	47
Figure 20: Datamonitor drug assessment summary of pipeline interferon therapies in development for HCV, 2008	65
Figure 21: Sales forecasts for marketed and new interferon therapies across the seven major markets 2007-2017	66
Figure 22: Phase IIb trial design for Albuferon in hepatitis C virus	72
Figure 23: Albuferon sales across the seven major markets 2007-2017	76
Figure 24: Locteron Phase IIa study design in hepatitis C virus	77
Figure 25: Locteron sales across the seven major markets 2007-2017	80
Figure 26: -IFNalpha-2b XL Phase IIa study design in hepatitis C virus	81
Figure 27: Overview of key hepatitis C virus targets	85
Figure 28: Datamonitor drug assessment summary of pipeline small molecule antiviral therapies in development for HCV, 2008	91
Figure 29: Small molecule antiviral drug sales across the seven major markets 2007-2017	92
Figure 30: R7128 Phase I Part 3 trial design	98
Figure 31: R-7128 sales across the seven major markets 2007	100
Figure 32: Telaprevir Phase III study in treatment-naïve hepatitis C virus patients	106
Figure 33: Overview of the REALIZE trial design for Telaprevir in hepatitis C virus	107
Figure 34: Overview of PROVE-1 study for Telaprevir in hepatitis C virus	108
Figure 35: Overview of PROVE-2 study for Telaprevir in hepatitis C virus	109
Figure 36: Telaprevir sales across the seven major markets 2007-2017	115
Figure 37: Overview of the SPRINT-1 trial for boceprevir in hepatitis C virus	118
Figure 38: Overview of telaprevir and boceprevir response rates	122
Figure 39: Boceprevir sales across the seven major markets 2007-2017	123
Figure 40: Overview of the OPERA-1 trial for TMC435350 in treatment-naïve patients with hepatitis C virus	124
Figure 41: VISER-1 design overview for taribavirin in hepatitis C virus	131
Figure 42: Phase IIb design overview for taribavirin in hepatitis C virus	133
Figure 43: Taribavirin sales across the seven major markets 2007-2017	135
Figure 44: Overview of pricing methodology for boceprevir and telaprevir	167
Figure 45: Overview of pricing methodology for R-7128	168
Figure 46: Overview of methodology used to derive volume for telaprevir	169
Figure 47: Overview of methodology used to derive volume for R-7128	169
Figure 48: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007	172

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