Pipeline Insight: Prostate Cancer Molecular Targeted Therapies will fulfill Unmet Needs in Castration-Resistant Disease

Published by: Datamonitor

Published: Aug. 14, 2009 - 154 Pages

Table of Contents

Overview

Catalyst

Summary

ABOUT DATAMONITOR HEALTHCARE

About the Oncology pharmaceutical analysis team

Executive Summary

Strategic scoping and focus

Datamonitor insight into the prostate cancer market

Contributing experts

Related reports

Upcoming reports

Table of Contents

1. Pipeline Overview and Dynamics

Key findings

Pipeline overview

Pipeline summary

Novel molecular targeted therapies and immunotherapies form the bulk of the current late-phase prostate cancer pipeline

Comparative forecasts

Datamonitor pipeline assessment summary

Key companies involved in the prostate cancer pipeline

Sanofi-Aventis

AstraZeneca

Novartis

Key R&D company strategies

The castration-resistant prostate cancer population holds the most commercial potential

The inclusion of molecular targeted therapies into prostate cancer treatment appears to be the way forward

2. Prostate cancer - Market Potential

Key findings

Definition

Introduction

The most common cancer type and second-leading cause of cancer-related death in males

Histology

The majority of prostate tumors are adenocarcinomas

Risk factors

Older age

Race

Family history

Hormones

Dietary factors

Symptoms

Symptoms frequently occur only at an advanced stage of prostate cancer

Screening and diagnosis

Measurement of PSA has proved fairly useful in the detection of prostate cancer, however, several issues need to be resolved

Patient segmentation

Prostate cancer is staged using the TNM system and a histologically-based Gleason score

Further segmentation dictates subsequent treatment options

Epidemiology

Seven major markets

Prostate cancer is a tumor associated with older men, therefore incidence is rising in line with the aging population

Potentially asymptomatic disease and a high rate of fatality from co-morbidities mean mortality from prostate cancer is not especially high

Rest of the world

Current treatment options

Antihormonal therapy

Cytotoxic therapy

Current comparator therapy

Taxotere (docetaxel; Sanofi-Aventis)

Unmet need in prostate cancer

More second-line therapy options are needed for metastatic castration-resistant prostate cancer

Less toxic therapy options are needed for first-line metastatic castration-resistant prostate cancer

Side effects from antihormonal therapies may affect compliance

Greater R&D interest in terms of targeted therapies

Target product profile versus current level of attainment

3. R&D Approach

Key findings

Clinical trial design in prostate cancer

Patient selection

Increasingly significant in the era of targeted treatment

Clinical trial duration

Sufficient follow-up is necessary to establish true clinical benefit

The advent of novel therapies

Diversity of targeted therapies will require an evolution in clinical trial design

Clinical trial endpoints in prostate cancer

Most oncology clinical trials designate multiple endpoints

Survival

Quality of life

Tumor response rates

Toxicity

Time to tumor progression

Effects on prostate-specific antigen and bone

4. Pipeline Analysis & Forecasts: Molecular Targeted Therapies

Key findings

Overview of the molecular targeted therapies

Pipeline summary

Comparative forecasts

Abiraterone (CB-7630; Cougar Biotechnology/BTG/Johnson & Johnson)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Phase II results show abiraterone to confer encouraging efficacy in both chemotherapy-naïve and in heavily pretreated castration-resistant prostate cancer

Clinical attractiveness

Encouraging Phase II data have resulted in a media furor over abiraterone, starting with controversy over use of the term ""hormone refractory""

Efficacy in a heavily pretreated patient population is striking in itself

Commercial attractiveness

Expansion into the first-line metastatic castration-resistant prostate cancer setting significantly increases abiraterone's commercial potential

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Aflibercept (VEGF-Trap; Regeneron/Sanofi-Aventis)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

A complete lack of prostate cancer-specific clinical trial data exists for aflibercept

Clinical attractiveness

A lack of clinical trial data makes it difficult to judge aflibercept's potential in prostate cancer

Commercial attractiveness

Presence in oncology field will aid commercialization of aflibercept

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Avastin (bevacizumab; Genentech/Roche/Chugai)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Phase II data show that Avastin in combination with standard first-line chemotherapy for castration-resistant prostate cancer has encouraging efficacy, however, overall survival has yet to be reported

Phase II data show that a neoadjuvant combination of Taxotere and Avastin results in a 39% partial response rate in high-risk localized prostate cancer

Clinical attractiveness

If Phase III trial data replicate Phase II results, then Avastin could become one of the few therapies to show a survival benefit in castration-resistant prostate cancer

Commercial attractiveness

Increasingly cost-conservative healthcare systems could restrict potential uptake of Avastin

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Sprycel (dasatinib; Bristol-Myers Squibb)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Sprycel shows both antitumor and anti-osteoclast activity in metastatic castration-resistant prostate cancer, which could have implications on bone metastases

Clinical attractiveness

No survival data have been reported for Sprycel in prostate cancer, making it difficult to judge its clinical attractiveness

Commercial attractiveness

Targeting patients with bone metastases could prove lucrative, however, Sprycel will suffer somewhat from being the last entrant to the prostate cancer market behind the competition

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Sutent (sunitinib; Pfizer)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Sutent shows antitumor activity in the both the first- and second-line treatment settings for metastatic castration-resistant prostate cancer, however, only the second-line setting has been pursued for further Phase III development

A neoadjuvant combination of Sutent and androgen deprivation therapy allowed 90% of patients in a Phase II study to undergo subsequent surgery, however, its fully utility requires further analysis of data

Clinical attractiveness

Sutent's association with only mild toxicities could help fulfill unmet needs in its target second-line metastatic population

Commercial attractiveness

Competition from Avastin and aflibercept is dampened by Pfizer's development of Sutent in the second-line setting, however, line extension into the first-line setting will be difficult

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Zibotentan (ZD-4054; AstraZeneca)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Phase II trial results show zibotentan to confer improved survival over placebo, with a possible effect on bone metastases

Clinical attractiveness

Use of placebo as a comparator is controversial

Effect on bone metastases may result in lower overall cost of treatment

Commercial attractiveness

Xinlay has already failed where zibotentan is now being investigated

AstraZeneca has extensive experience in the prostate cancer market

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

5. Pipeline Analysis & Forecasts: Cytotoxic Therapies

Key findings

Overview of the cytotoxic therapies

Pipeline summary

Comparative forecasts

Cabazitaxel (XRP-6258; Sanofi-Aventis)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

A dearth of clinical trial data exist for cabazitaxel in prostate cancer

Clinical attractiveness

Complete lack of reported data makes it hard to judge cabazitaxel's clinical potential

Commercial attractiveness

Sanofi-Aventis's extensive experience in the prostate cancer market will be invaluable, however, the impending entry of generic docetaxel could hinder cabazitaxel's uptake

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

6. Pipeline Analysis & Forecasts: Immunotherapies

Key findings

Overview of the immunotherapies

Pipeline summary

Comparative forecasts

Ipilimumab (MDX-010; Medarex/Bristol-Myers Squibb)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Ipilimumab results in fall in PSA with or without radiotherapy in both chemotherapy-naïve patients and those who have received prior chemotherapy

Early results from a Phase II study investigating ipilimumab alongside standard antihormonal therapy and radiotherapy show extensive tumor regression in two patients

Clinical attractiveness

Incidence of immune-related adverse events may be related to the drug's efficacy

Pfizer's negative experience with tremelimumab may tarnish ipilimumab's reputation

Commercial attractiveness

Collaboration agreement with Bristol-Myers Squibb will be highly advantageous for Medarex

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

Provenge (sipuleucel-T; Dendreon)

Drug overview

Drug profile

Key historical events

SWOT analysis

Clinical trial data

Phase III D9901 study shows Provenge to confer a statistically significant improvement in overall survival, however, it failed to meet its primary endpoint of improving time to progression

Phase III IMPACT study shows Provenge to confer a statistically significant improvement in overall survival, therefore meeting the trial's primary endpoint

Combined D9901 and D9902A subgroup analysis shows Taxotere administered upon disease progression to Provenge-treated patients results in a prolonged survival benefit

Preliminary results from the PROTECT trial suggest Provenge's efficacy in early-stage prostate cancer

Clinical attractiveness

Uncertainty surrounds the cancer vaccines

Provenge may represent a viable alternative for those patients precluded from Taxotere therapy

Potential for line extension into the adjuvant setting

Commercial attractiveness

Provenge has initiated a high level of controversy

Provenge's probable high cost and complex manufacture may be offset by being the first vaccine to demonstrate a survival benefit in prostate cancer

Provenge's commercial potential could be enhanced by the backing of an established oncology player

Datamonitor drug assessment summary

Satisfaction of unmet needs

Forecasts to 2018

7. Innovative Early-Stage Approaches

Key findings

Overview of early-stage innovative projects

Epidermal growth factor receptor

Prostate-specific membrane antigen

Akt

The future of treatment in prostate cancer

Greater understanding of cancer evolution should result in a large range of potential drug targets

Longer term control of tumors with reduced toxicity is crucial

Improvements in diagnostics and prognostic analysis will enhance cost-effectiveness of treatment

Enhanced preventative strategies will ease the disease burden

Bibliography

APPENDIX

Methodology

Epidemiology forecasts

Product forecasts

Datamonitor drug assessment scorecard

About Datamonitor

About Datamonitor Healthcare

About the Oncology analysis team

Datamonitor consulting

Disclaimer

List of Tables

Table 1: Late-phase pipeline products in development for prostate cancer, 2009

Table 2: Sales forecasts for late-phase prostate cancer pipeline products in the seven major markets, 2009-2018 ($m)

Table 3: Sanofi-Aventis marketed and pipeline oncology portfolio, 2009

Table 4: AstraZeneca marketed and pipeline oncology portfolio, 2009

Table 5: Novartis marketed and pipeline oncology portfolio, 2009

Table 6: Incidence rates of prostate cancer per 100,000 population in the US by race, 2000-04

Table 7: Crude incidence rates of prostate cancer per 100,000 population in the seven major pharmaceutical markets, 2002

Table 8: Estimated incidence of prostate cancer in the seven major pharmaceutical markets, 2002-2018

Table 9: Approved antihormonal therapies for prostate cancer, 2009

Table 10: Approved cytotoxic therapies for prostate cancer, 2009

Table 11: Taxotere (docetaxel) - drug profile, 2009

Table 12: Ability of Taxotere to meet unmet needs in prostate cancer, 2009

Table 13: Targeted therapy subgroup mechanisms of action

Table 14: Late-phase molecular targeted therapies in development for prostate cancer, 2009

Table 15: Forecast assumptions for molecular targeted therapy prostate cancer pipeline products across the seven major markets, 2009 (1 of 2)

Table 16: Forecast assumptions for molecular targeted therapy prostate cancer pipeline products across the seven major markets, 2009 (2 of 2)

Table 17: Sales forecasts for molecular targeted therapy prostate cancer pipeline products in the seven major markets, 2009-2018 ($m)

Table 18: Abiraterone - drug profile, 2009

Table 19: Abiraterone: key historical events

Table 20: Clinical development of abiraterone in prostate cancer, 2009

Table 21: Ability of abiraterone to meet unmet needs in prostate cancer, 2009

Table 22: Sales forecast for abiraterone in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 23: Aflibercept - drug profile, 2009

Table 24: Aflibercept: key historical events

Table 25: Clinical development of aflibercept in prostate cancer, 2009

Table 26: Ability of aflibercept to meet unmet needs in prostate cancer, 2009

Table 27: Sales forecast for aflibercept in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 28: Avastin - drug profile, 2009

Table 29: Avastin: key historical events

Table 30: Clinical development of Avastin in prostate cancer, 2009

Table 31: Ability of Avastin to meet unmet needs in prostate cancer, 2009

Table 32: Sales forecast for Avastin in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 33: Sprycel - drug profile, 2009

Table 34: Sprycel: key historical events

Table 35: Clinical development of Sprycel in prostate cancer, 2009

Table 36: Ability of Sprycel to meet unmet needs in prostate cancer, 2009

Table 37: Sales forecast for Sprycel in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 38: Sutent - drug profile, 2009

Table 39: Sutent: key historical events

Table 40: Clinical development of Sutent in prostate cancer, 2009

Table 41: Ability of Sutent to meet unmet needs in prostate cancer, 2009

Table 42: Sales forecast for Sutent in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 43: Zibotentan - drug profile, 2009

Table 44: Zibotentan: key historical events

Table 45: Clinical development of zibotentan in prostate cancer, 2009

Table 46: Ability of zibotentan to meet unmet needs in prostate cancer, 2009

Table 47: Sales forecast for molecular targeted therapy prostate cancer pipeline products in the seven major markets, 2009-2018 ($m)

Table 48: Cytotoxic therapy subgroup mechanisms of action

Table 49: Late-phase cytotoxic therapy in development for prostate cancer, 2009

Table 50: Forecast assumptions for cytotoxic therapy prostate cancer pipeline product across the seven major markets, 2009

Table 51: Sales forecasts for cytotoxic therapy prostate cancer pipeline product in the seven major markets, 2009-2018 ($m)

Table 52: Cabazitaxel - drug profile, 2009

Table 53: Cabazitaxel: key historical events

Table 54: Clinical development of cabazitaxel in prostate cancer, 2009

Table 55: Ability of cabazitaxel to meet unmet needs in prostate cancer, 2009

Table 56: Sales forecast for cabazitaxel in prostate across the seven major markets, 2009-2018 ($m)

Table 57: Immunotherapy subgroup mechanisms of action

Table 58: Late-phase immunotherapies in development for prostate cancer, 2009

Table 59: Forecast assumptions for immunotherapy prostate cancer pipeline products across the seven major markets, 2009

Table 60: Sales forecasts for immunotherapy prostate cancer pipeline products in the seven major markets, 2009-2018 ($m)

Table 61: Ipilimumab - drug profile, 2009

Table 62: Ipilimumab: key historical events

Table 63: Clinical development of ipilimumab in prostate cancer, 2009

Table 64: Ability of ipilimumab to meet unmet needs in prostate cancer, 2009

Table 65: Sales forecast for ipilimumab in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 66: Provenge - drug profile, 2009

Table 67: Provenge: key historical events

Table 68: Clinical development of Provenge in prostate cancer, 2009

Table 69: Ability of Provenge to meet unmet needs in prostate cancer, 2009

Table 70: Sales forecast for Provenge in prostate cancer across the seven major markets, 2009-2018 ($m)

Table 71: Top 10 early-stage prostate cancer drug targets, 2009

Table 72: Datamonitor drug assessment parameters

List of Figures

Figure 1: Prostate cancer pipeline split by development phase and drug class, 2009

Figure 2: Datamonitor drug assessment summary for late-phase pipeline products in development for prostate cancer, 2009

Figure 3: Incidence and mortality from prostate cancer in 2009 and 2018 across the seven major pharmaceutical markets

Figure 4: Top 5 rest of world countries with highest incidence of prostate cancer, 2009-2018

Figure 5: Key unmet needs in prostate cancer, 2009

Figure 6: Datamonitor drug assessment summary for molecular targeted therapies in development for prostate cancer, 2009

Figure 7: Abiraterone SWOT analysis, 2009

Figure 8: Phase II COU-AA-002 results for first -line abiraterone plus prednisone in castration-resistant prostate cancer

Figure 9: Phase II COU-AA-003 results for second -line abiraterone in castration-resistant prostate cancer

Figure 10: Phase II COU-AA-004 results for second/third-line abiraterone and prednisone in metastatic castration-resistant prostate cancer

Figure 11: Datamonitor drug assessment summary for abiraterone in prostate cancer, 2009

Figure 12: Aflibercept SWOT analysis, 2009

Figure 13: Datamonitor drug assessment summary for aflibercept in prostate cancer, 2009

Figure 14: Avastin SWOT analysis, 2009

Figure 15: Initial Phase II results investigating first-line Avastin, Taxotere and estramustine in metastatic castration-resistant prostate cancer

Figure 16: Phase II results investigating first-line Avastin, Taxotere and Thalomid in metastatic castration-resistant prostate cancer

Figure 17: Phase II results investigating neoadjuvant Taxotere and Avastin in high-risk localized prostate cancer

Figure 18: Datamonitor drug assessment summary for Avastin in prostate cancer, 2009

Figure 19: Sprycel SWOT analysis, 2009

Figure 20: Phase I/II results investigating first/second-line Sprycel and Taxotere metastatic castration-resistant prostate cancer

Figure 21: Phase II results investigating first-line Sprycel in progressive metastatic castration-resistant prostate cancer

Figure 22: Datamonitor drug assessment summary for Sprycel in prostate cancer, 2009

Figure 23: Sutent SWOT analysis, 2009

Figure 24: Phase II results investigating first-line Sutent, Taxotere and prednisone in metastatic castration-resistant prostate cancer

Figure 25: Phase II results investigating second/third-line Sutent in progressive metastatic castration-resistant prostate cancer following failure of Taxotere-based chemotherapy

Figure 26: Phase II results investigating neoadjuvant Sutent plus androgen deprivation therapy in high-risk localized prostate cancer prior to radical prostatectomy

Figure 27: Datamonitor drug assessment summary for Sutent in prostate cancer, 2009

Figure 28: Zibotentan SWOT analysis, 2009

Figure 29: Phase II study investigating first-line zibotentan in castration-resistant prostate cancer with bone metastases

Figure 30: Datamonitor drug assessment summary for zibotentan in prostate cancer, 2009

Figure 31: Datamonitor drug assessment summary for cytotoxic therapies in development for prostate cancer, 2009

Figure 32: Cabazitaxel SWOT analysis, 2009

Figure 33: Datamonitor drug assessment summary for cabazitaxel in prostate cancer, 2009

Figure 34: Datamonitor drug assessment summary for immunotherapies in development for prostate cancer, 2009

Figure 35: Ipilimumab SWOT analysis, 2009

Figure 36: Phase I/II study investigating first/second-line ipilimumab alone and in combination with radiotherapy in metastatic castration-resistant prostate cancer

Figure 37: Datamonitor drug assessment summary for ipilimumab in prostate cancer, 2009

Figure 38: Provenge SWOT analysis, 2009

Figure 39: Phase III D9901 results investigating Provenge in asymptomatic metastatic castration-resistant prostate cancer

Figure 40: Phase III IMPACT results investigating Provenge in asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer

Figure 41: Analysis of patient subgroup from Phase III D9901 and D9902A studies who received Taxotere following Provenge or placebo

Figure 42: Preliminary Phase III PROTECT results investigating Provenge in hormone-sensitive non-metastatic prostate cancer

Figure 43: Datamonitor drug assessment summary for Provenge in prostate cancer, 2009

Figure 44: Early-stage prostate cancer pipeline split by drug class, 2009

Figure 45: Datamonitor drug assessment summary for molecular targeted therapies in development for prostate cancer, 2009

Abstract

• Examination of the prostate cancer pipeline with in-depth clinical and commercial profiles of Phase III candidates
• Seven major pharmaceutical market sales forecasts for Phase III pipeline products through to 2018 with product-specific assumptions
• Segmentation and analysis of the current prostate cancer pipeline by developmental phase, drug class and company
• Insight and analysis of market potential including commercial opportunity, epidemiology and discussion of unmet needs

• Identify key drugs and companies within the prostate cancer pipeline based on sales forecasts to 2018 and Datamonitor drug assessment
• Characterize unmet need and poorly served patient subsets within prostate cancer and assess the potential for pipeline products to fulfill them
• Assess the shifting prostate cancer market dynamic and how future treatment will incorporate pipeline products

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