Stakeholder Opinions: Hepatocellular Carcinoma - Growing Market Seeks New Players

SUMMARY

Hepatocellular carcinoma (HCC) is the fifth commonest cancer worldwide with ca. one million new cases diagnosed annually. Datamonitor estimates that the incidence of HCC in the seven major pharma markets will continue to rise over the next decade. There is no gold standard therapy - the market is characterized by high levels of unmet need, large patient potential and high commercial potential.

Scope of this report

• Overview of hepatocellular carcinoma, including the biology of HCC and liver cirrhosis, risk factors, epidemiology, staging and treatment options
• Opinion leader interviews discussing current treatment practices, key unmet needs and the future of HCC therapy
• Analysis of pipeline products for HCC and potential use of molecular targeted agents in the management of HCC
• Novel local ablation treatments used to manage HCC

Research and analysis highlights

There have been no advances in the treatment of HCC for the last decade. A lack of gold standard therapy for HCC means that physicians are eager for new pharmacological interventions that offer even modest improvements in efficacy and disease outcome.

HCC patients are clinically underserved and there is a lack of consensus in staging and screening methods for these patients. Opinion leaders frequently criticized clinical trial design for HCC patients with true tumor response being obscured by heterogeneous patient populations and poorly defined end points.

Thymitaq (Eximias) and T67 (Amgen) are in the final stages of clinical trials and may be the first agents to be approved for HCC, offering hope for improvements in HCC treatment.

Key reasons to read this report

• Understand the epidemiology and current clinical treatment of HCC
• Identify future market opportunities by examining current unmet needs and how current therapy and clinical trial design fails HCC patients
• Plan new product development programs based on an understanding of physician expectation of molecular targeted therapy for HCC

TABLE OF CONTENTS

CHAPTER 1 EXECUTIVE SUMMARY

Scope

Datamonitor insight into the hepatocellular carcinoma market

CHAPTER 2 INTRODUCTION

Disease overview

Introduction

The liver

Liver function

The damaged liver and its implications

Hepatocellular carcinoma

Epidemiology

Risk factors

Hepatitis infection

Hepatitis B infection

Hepatitis C infection

Liver cirrhosis

Alflatoxin

Hemochromatosis

Screening

Alfa-fetoprotein (AFP)

Hepatic ultrasound

Computed tomography

Diagnosis

Staging

Okuda

Cancer of the liver Italian program (CLIP)

Chinese University Prognostic Index (CUPI)

CHAPTER 3 CURRENT TREATMENT OPTIONS

Introduction

Surgery

Liver transplantation

Radiotherapy

Chemotherapy

Doxorubicin: most commonly used cytotoxic in HCC management

Poorly designed clinical trials contribute to variability of response rates

Other treatments

Radiofrequency ablation (RFA)

Opportunity for immunotherapy?

Percutaneous ethanol injection (PEI)

Cryoablation

Chemoembolization (TACE)

Hepatic arterial pumps

Conclusions

CHAPTER 4 CURRENTLY AVAILABLE DRUG THERAPIES

Liver disease limits the use of cytotoxics in HCC

Doxorubicin

Cardiotoxicity associated with doxorubicin

Reformulations of doxorubicin

Doxorubicin combinations

Doxorubicin, cisplatin, 5-FU, IFN-α (PIAF)

Cisplatin

Reformulations of cisplatin

Cisplatin combinations

Epirubicin

Interferon

Interferon combinations

CHAPTER 5 UNMET CLINICAL NEEDS IN HCC PHARMACOTHERAPY

Lack of any efficacious agent

Poorly designed clinical trials

Management of HCC patients

Lack of screening programs

Lack of promising pipeline products

CHAPTER 6 PIPELINE ANALYSIS

Thymitaq

Phase III

T67

Clinical data

Phase II trials

Phase I trials

T67 will benefit from acquisition by Amgen

Irofulven (MGI 114)

Phase II

Identifying responder subgroups

Targeted therapy for HCC

Thalidomide

Thalidomide in HCC

Thalidomide as a palliative care option

Does the eitology of HCC determine the response to thalidomide?

Thalidomide in combination with other agents.

Thalidomide and epirubicin

Thalidomide, α-interferon +/- octreotide

Thalidomide in combination with TACE

A role for thalidomide in HCC

Targeting VEGF/VEGFR receptor pathways

Avastin (bevacizumab)

Drug overview

BAY 43-9006 (sorafenib)

Epidermal growth factor receptor (EGFR)

Iressa (gefitinib)

Iressa in HCC

Tarceva (erlotinib)

INTERVIEW TRANSCRIPTS

US OPINION LEADER

US OPINION LEADER

US OPINION LEADER

EUROPEAN OPINION LEADER

EUROPEAN OPINION LEADER AND SURGICAL COLLEAGUE

EUROPEAN OPINION LEADER

EUROPEAN OPINION LEADER

CHAPTER 7 APPENDIX

References

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcares research and analysis methodologies

Datamonitor Healthcares therapy area capabilities

About the Oncology analysis team

List of Tables

Table 1: Incidence forecasts of HCC in the seven major pharmaceutical markets, 2004-12

Table 2: Incidence forecasts of HCC in the seven major pharmaceutical markets, 2004-12

Table 3: Incidence forecast of HCC in males in the seven major pharmaceutical markets, 2004-12

Table 4: Incidence forecast for HCC in females in the seven major pharmaceutical markets, 2004-12

Table 5:TNM definitions

Table 6: Child-Pugh classification

Table 7: Okuda staging system

Table 8: CLIP scoring system for HCC

Table 9: Multicenter validation of CUPI system

Table 10: Improvement in five-year survival rates in HCC patients undergoing liver transplantation

Table 11: Comparison of RFA and surgical resection in terms of recurrence rates and overall survival

Table 12: Comparison of RFA in HCC patients with Child-Pugh class A and class B Table 13: Arterial embolization or chemoembolization compared to systemic treatment for hepatocellular carcinoma

Table 14: Five-year disease-free survival (stage T1-T2)

Table 15: Commonly used drug regimes in the management of HCC

Table 16: Combining doxorubicin with cisplatin does not increase response rate

Table 17: Phase III and Phase II trials for HCC

Table 18: Reduction of Thymitaq related toxicity in ETHECC trial

Table 19: Phase II trial results of Thymitaq

List of Figures

Figure 1: The Portal system

Figure 2: Incidence forecast of HCC in the seven pharmaceutical markets, 2004-12

Figure 3:HBV prevalence in the seven major markets, 2002

Figure 4: HBV disease progression

Figure 5: HCV prevalence in the seven major markets, 2002

Figure 6: HCV disease progression leading to HCC.

Figure 7: Current treatment options for HCC

Figure 8: Phase II studies of doxorubicin in the management of HCC

Figure 9: Radiofrequency ablation

Figure 10: Cryoablation of hepatocellular carcinoma

Figure 11: Transcatheter arterial chemoembolization

Figure 12: Hepatic-arterial infusion pump

Figure 13:Unmet clinical need in HCC pharmacotherapy

Figure 14: HCV- compared to HBV-related HCC in response to thalidomide