Market Report Source

Overview

Introduction
An estimated 10 million people in the seven major markets have chronic HCV. The current standard of care, pegylated interferon (Peg-IFN) plus ribavirin (RBV), achieves long-term disease remission in approximately half of those receiving treatment. More efficacious therapies are required to improve treatment success in difficult-to-treat patients, in particular patients with HCV genotype 1.

Scope
Comprehensive overview of compounds in clinical development for HCV, including interferons, small molecule antivirals and immunomodulators
Revenue forecasts from 20062015 for key late-stage compounds and the HCV market as a whole
Appraisal of clinical trial design highlighting the rising complexity associated with patient stratification and the trend towards multidrug therapy
Expert opinion on late-stage drugs and their potential use, outlook on HCV therapy evolution and analysis of prevailing unmet needs

Highlights
Concomitant with new drug launches from 2009 onwards, the HCV market is estimated to double by 2010 and potentially quadruple by 2015. Growth will be driven mainly by the rapid uptake of new drugs, the premium prices these will be able to command and the expected increase in treatment rates.

Vertex’ protease inhibitor VX-950 is the most promising antiviral in late-stage development. The drug has demonstrated potent reduction of HCV RNA following 14 or 28 days of therapy, prompting Vertex to assess the ability of VX-950 to shorten treatment duration to 12 weeks. Blockbuster potential will be conditional on favorable long-term toxicity.

HCV therapy is expected to evolve towards multidrug therapy consisting of drugs with complementary mechanisms of action. In an increasingly crowded market, attributes other than efficacy will gain importance, including favorable tolerability, convenient dosing, and lack of drug-drug interactions, particularly in HIV/HCV co-infection.

Reasons to Purchase
Understand key growth drivers in the mid to long-term HCV market and quantify the future size, scope and potential for new products
Optimize R&D strategies and clinical trial design in line with evolving treatment paradigms
Benchmark the HCV pipeline against currently marketed products and market needs

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Infectious Diseases & Respiratory pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Contributing experts

Datamonitor insight into the HCV market

The HCV market is expected to grow from $2.2 billion in 2005 to $4.4 billion in 2010 and $8.8 billion in 2015. Growth will be driven mainly by the rapid uptake of new drugs and potentially the use of multiple drugs in the same treatment regime, the premium pricing these will be able to command and the increase in the number of patients seeking treatment

Vertex’ protease inhibitor VX-950, the most potent drug in the late-stage HCV pipeline, is anticipated to be the key growth driver, overshadowing Schering-Plough’s protease inhibitor SCH-503034 and Idenix/Novartis’s polymerase inhibitor NM283. VX-950’s success will be conditional on the drug confirming superior efficacy rates and favorable long-term toxicity

HCV trial design is becoming increasingly complex. The heterogeneity of the overall patient pool requires stratification by treatment status, HCV genotype and comorbidities. The exploration of multidrug therapy, weight-based dosing and ideal treatment duration has increased overall trial sizes. Current therapy trial design reflects uncertainty about the future face of HCV therapy

With only half of all HCV patients benefiting from current therapy, medical unmet needs are high. Higher efficacy with regard to the ability to achieve SVR remains the key, followed by better tolerability. SVR rates are particularly low in difficult-to-treat patients

Key metrics

CHAPTER 2 HCV PIPELINE ANALYSIS

Pipeline overview

Small molecule antivirals dominate the HCV pipeline

The HCV pipeline contains drugs with various mechanisms of action

Double-digit growth driven by the launch of potent HCV inhibitors will lead to a doubling of the HCV market by 2010

Key companies involved in the HCV pipeline

Established players are losing market share to newcomers

Roche – Pegasys still growing strong

Schering-Plough – SCH-503034 to fill the gap

Vertex – expanding the market with VX-950

Novartis – building a broad arsenal of antivirals

CHAPTER 3 PATIENT POTENTIAL

Hepatitis C disease definition and progression

HCV genotype 1 currently accounts for the majority of chronic infections

Genotype frequency: new infections may not mirror the current chronic patient pool

While past HCV transmission occurred mainly through contaminated blood products, most new infections currently occur via injection drug use

HCV readily establishes a chronic infection that can progress to liver cirrhosis and cancer

As a result of the silent nature of chronic HCV, patients are usually diagnosed at advanced stages of liver fibrosis

The number of patients presenting with HCV-related complications is set to rise

HCV epidemiology and patient segmentation

Chronic HCV is widespread on a global basis, with prevalence varying significantly by geographical region

Estimates for chronic HCV prevalence in the seven major markets

Chronic HCV is more prevalent among men, in older age groups, and individuals of African origin

Significantly higher rates of HCV prevalence are found in IDUs, HIV patients, and individuals receiving renal replacement therapy

Patient segmentation takes into account both patient and virus-specific factors

Drug development focuses on HCV genotype 1

Nonresponders and relapsers currently left without treatment options

HCV/HIV co-infection – a notoriously difficult-to-treat patient subgroup

Recurrent HCV post-transplant – current treatment options suffer from major limitations

The HCV market is characterized by high unmet need

Higher efficacy remains the most important product-specific unmet need

Higher efficacy, in particular in HCV genotype 1

Better tolerability

Shorter treatment duration

Less frequent dosing

Other product-specific unmet needs

Patient-specific unmet needs

Diagnosis and treatment rates are currently low, but are expected to increase concomitant with market entry of new drugs

Certain population subgroups achieve moderate or limited success with current treatment options

CHAPTER 4 R&D APPROACH

Effective treatment of chronic HCV requires combination therapy

From interferon monotherapy to pegylated interferon plus ribavirin combination therapy

Moderate success with interferon monotherapy

Breakthrough with ribavirin

Pegylation of the interferon molecule reduces dosing frequency while increasing efficacy

Pegylated interferon plus ribavirin combination therapy is the current standard of care

Both pegylated interferon and ribavirin have broad mechanisms of action

Little differentiation between the two available combination therapies

The future of Peg-IFN-based therapy lies in tailoring therapy to the patient

HCV pipeline drugs fall into five major drug classes

Small molecule antivirals directly inhibit key steps in the viral lifecycle

NS3 protease inhibitors are the most promising drug class

NS5B polymerase inhibitors are less potent than the protease inhibitors but might have an important role as part of multidrug therapy

Other direct HCV inhibitors

Interferons act by inducing a local and systemic immune response

Interferons with reduced dosing frequency may lower the incidence of side effects

Immunomodulators

Will Toll-Like Receptor (TLR) agonists live up to the expectations?

Other immunomodulators

Therapeutic vaccines have been difficult to develop

Clinical trial design in HCV is becoming increasingly complex

Patient stratification according to genotype and treatment experience is a must

Further levels of patient stratification require ever larger studies

Moving toward multidrug therapy

Clinical trial endpoints in HCV focus on antiviral efficacy

Virologic response is the key measure of antiviral efficacy

RVR, EVR, ETR and the all-important SVR

Viramidine trials have included the incidence of anemia as a co-primary endpoint

Study endpoints other than virologic response rates will become increasingly important

CHAPTER 5 INTERFERONS LATE-STAGE DRUG ANALYSIS

Overview for interferons in late-stage development for HCV

Pipeline summary

Definition of current comparator therapy

Pegylated interferon has limited efficacy in HCV genotype 1 and is associated with adverse events

Long acting interferons

Albuferon – albumin fusion to interferon reduces dosing frequency

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecast to 2015

Omega interferon & Omega DUROS

Drug overview

Key clinical trial data

Datamonitor comments

CHAPTER 6 SMALL MOLECULE ANTIVIRALS LATE-STAGE DRUG ANALYSIS

Overview for small molecule antivirals in late-stage development for HCV

Pipeline summary

Definition of current comparator therapy

RBV has limited antiviral efficacy and causes hemolytic anemia

IMPDH inhibitors

Viramidine – less toxic than RBV, but doubts regarding non-inferiority still prevail

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

NS5B RNA-dependent RNA polymerase inhibitors

Valopicitabine (NM-283) – commercial success relies on combination therapy with protease inhibitors

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

NS3 protease inhibitors

VX-950 – unprecedented high potency and potential for shorter treatment duration

Drug overview

Key clinical trial data

Pharmacokinetic boosting with ritonavir may improve dosing

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

SCH-503034 – overshadowed by VX-950?

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

Other small molecule antivirals

Celgosivir (MX-3253) – antiviral effect through inhibition of a cellular enzyme

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

Comparison of small molecule antivirals in late-stage development

Late-stage developmental compounds recently discontinued

Merimepodib (VX-497) – development post-METRO unlikely

UT-231B

JTK-003

HCV-086

Ciluprevir (BILN-2061)

Unexpected toxicity in animals

R803

Levovirin

CHAPTER 7 IMMUNOMODULATORS LATE-STAGE DRUG ANALYSIS

Overview for immunomodulators in late-stage development for HCV

Pipeline summary

Definition of current comparator therapy

Toll-like receptor agonists

CpG 10101 (Actilon) – a TLR9 agonist with a dual mode of action

Drug overview

Key clinical trial data

Patient potential

Marketing factors

Datamonitor comments

Forecasts to 2015

Late-stage developmental compounds recently discontinued

Histamine dihydrochloride (Ceplene)

FK778

CHAPTER 8 DEVELOPMENTAL HCV THERAPEUTICS EXCLUDED FROM THE FORECAST

Developmental HCV drugs in Phase I

ANA-975 – Anadys’s TLR7 agonist

R1626 – Roche’s polymerase inhibitor

HCV-796 – ViroPharma’s polymerase inhibitor

XTL-2125 – XTL’s polymerase inhibitor

GS-9132 (ACH-806) – Achillion’s & Gilead’s protease inhibitor

Developmental HCV therapeutics excluded for other reasons

Therapeutic vaccines

INNO101 (InnoVac-C, HCV-E1 vaccine)

IC-41

Novartis’s HCV vaccines

Drugs in development for recurrent HCV post-transplant and HCV-related liver disease

IDN-6556

Civacir

XTL-6865 (XTL-002)

Drugs with uncertain commercial potential

Interferon beta

Zadaxin

IFN alfa-2b XL

Peg-IFN alfacon-1 (consensus IFN)

Virostat

EMZ-702

AVI-4065

EHC-18

APPENDIX

Methodology & bibliography

Forecasting methodology

Chronic HCV prevalence

HCV treatment rates

Product penetration rates

Product pricing

Pricing of marketed drugs

Average duration of HCV therapy

Summary of HCV epidemiology forecast

Estimation of product launch dates

Estimation of pegylated and standard interferon sales accounted for by chronic HCV

Developmental product patent expiry dates

Report methodology

Bibliography

Journals

Conference abstracts

Press releases

Datamonitor products

Miscellaneous

Websites

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s therapy area capabilities

About the Infectious Diseases & Respiratory analysis team

Disclaimer

List of Tables

Table 1: HCV pipeline overview

Table 2: Commercially attractive late-stage developmental HCV drugs included in the sales forecast

Table 3: HCV drug sales by class, 2005-2015

Table 4: Geographical distribution of HCV genotypes

Table 5: Adjusted prevalence of HCV RNA positive individuals in the seven major markets, 2006

Table 6: HIV/HCV co-infection in the seven major markets

Table 7: The efficacy of the current standard of care is genotype-dependent, being lowest for HCV genotypes 1 and 4

Table 8: Dosing schedule for Peg-Intron and Rebetol combination therapy

Table 9: Dosing schedule for Pegasys and Copegus combination therapy

Table 10: Patients who achieve RVR and EVR are more likely to achieve SVR

Table 11: Key late-stage interferons

Table 12: The median half-life of Albuferon is significantly higher than that of both Pegasys and PEG-Intron

Table 13: Albuferon: key facts

Table 14: 48-week and 24-week results for US Albuferon combination trial in nonresponders show dose-dependent antiviral activity

Table 15: 12-week results for the Phase II Albuferon combination trial in HCV genotype 1 treatment-naïve patients

Table 16: Global sales forecast for Albuferon, 2010-2015

Table 17: Omega DUROS: key facts, 2006

Table 18: EVR data for Phase II trial of Omega IFN in combination with RBV, November 2005

Table 19: Key late-stage small molecule antivirals, 2006

Table 20: Viramidine: key facts,2006

Table 21: Efficacy results for VISER 1

Table 22: Stratification of patients supports weight-based viramidine dosing

Table 23: The accumulation of viramidine in plasma and red blood cells (RBCs) is lower than that of RBV

Table 24: Global sales forecast for viramidine, 2009-2015

Table 25: Valopicitabine (NM283): key facts, 2006

Table 26: Partial 24-week data for the NM283 Phase IIb trial in HCV genotype 1 nonresponders

Table 27: Following the incidence of dose-dependent GI effects, the maximum dose for HCV genotype 1 nonresponders was reduced to 400mg from the original 800mg

Table 28: Partial 4-week results for the Phase IIb NM283 trial in treatment-naïve HCV genotype 1 infected patients

Table 29: Global sales forecast for NM283, 2009-2015

Table 30: VX-950: key facts, 2006

Table 31: Preliminary 4-week results of VX-950’s triple combination Phase II study in treatment-naïve, genotype-1 infected HCV patients