Abstract
Overview
Introduction
The current focus on biomarker discovery is a result of an improved
understanding of the biologic basis for carcinogenesis. The increasing number
of potential drug targets and a plethora of diverse, new developmental agents
have stimulated the search for biomarkers that can reduce the time, cost and
attrition rates prevalent in oncology drug development.
Scope
- The role of biomarkers in optimizing patient selection and treatment
outcomes and in expediting oncology drug development.
- Biomarker classification in oncology.
- Regulator opinion on the integration of novel, valid and relevant
biomarker endpoints into the design of oncology clinical trials.
- Key commercial benefits and risks of incorporating predictive biomarkers
into oncology drug development.
Report Highlights
It is hoped that the increased adoption of biomarker use in oncology will
enable early proof-of-concept studies for novel therapeutic targets;
accelerate the adoption of population-enrichment strategies for clinical trial
recruitment; and increase the use of biomarker endpoints as surrogates for
clinical benefit in oncology clinical trials.
Advances in imaging analysis technology have shed new light on cancer
progression by enabling the precise measurement of small changes in structure
and function over time. Image-based biomarkers have been singled out by the
FDA as promising tools for every stage of drug development, from preclinical
research to the approval process.
While targeting specific genotypes in clinical trials increases the
opportunity to demonstrate clinical benefit, developers are concerned about
how an increasingly fragmented cancer market may limit a drug's commercial
potential. There is already skepticism among physicians about how readily
Pharma will adopt a more 'personalized' approach.
Reasons to Purchase
- Understand how tumor biomarkers will impact on oncology drug development
as the paradigm to targeted treatment evolves.
- Assess opportunities and risks for novel oncology biomarker development
and commercialization.
- Drive drug development strategies that incorporate prognostic or
predictive biomarkers.
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- CHAPTER 1 EXECUTIVE SUMMARY
- CHAPTER 2 BIOMARKER USE IN DRIVING EFFICIENCIES IN THE COMMERCIALIZATION
OF NOVEL ONCOLOGY PHARMACOTHERAPY
- Defining biomarkers in relation to the diagnosis and treatment of cancer
- Using biomarkers to mitigate productivity-constraining challenges in
oncology drug development
- Early changes in PSA may predict efficacy of novel developmental
agents targeting prostate cancer
- Cancer biomarkers have the potential to greatly enhance the screening,
diagnosis and treatment decision-making process
- Ideal biomarker requirements vary with their proposed clinical use
- Collaborative initiatives aim to facilitate biomarker discovery
- Defining prognostic and predictive biomarkers
- Prognostic biomarkers can be classified as 'biological progression
biomarkers' or 'risk biomarkers'
- Predictive biomarkers provide a measure of the impact of drug and
non-drug interventions
- FDA has designated 'Type 2' cancer biomarkers as valid surrogates of
clinical benefit
- Biomarker validation remains a major challenge for the scientific
community
- Lack of rigor and consistency in novel biomarker validation has
resticted their acceptance among the scientific and clinical community
- Current biomarkers and their clinical and commercial use
- Many cancer biomarkers in current clinical use are used to guide the
selection of novel targeted treatments
- Four biomarker assays dominate the marketplace and collectively
generated global sales of $860m in 2003
- CHAPTER 3 IMAGING BIOMARKERS ARE BEING ADOPTED WITH INCREASING FREQUENCY
- Functional imaging is generating the greatest interest as a tool to aid
drug development
- Focus on F-18-deoxyglucose Positron-Emission Tomography imaging to
facilitate early assessment of cancer drug efficacy
- Payer enthusiasm for PET scanning is shared by regulators
- Dynamic contrast-enhanced magnetic resonance imaging may provide an
valuable early assessment of the efficacy of angiogenesis inhibitors
- Developers show early signs of adopting DCE-MRI to assess the
antiangiogenic activity of novel developmental agents
- Developers will need to partner with functional imaging experts to
ensure quality assurance in functional imaging applications
- CHAPTER 4 NEXT GENERATION BIOMARKERS WILL FOCUS ON GENOMIC- AND
PROTEOMIC-BASED APPROACHES
- Protein function rather than protein quantification may be the more
salient approach
- Early demonstration of how protein expression profiles may help guide
pharmacotherapy decisions
- Genomic biomarkers herald the future
- Affymetrix-Roche's Amplichip represents the first FDA-approved
genomic-based prognostic tool
- Diagnostic biomarket market expected to reach $3 billion annually
- Single DNA-based biomarkers likely to be of little prognostic or
predictive value
- Epigenetic changes and mutations in oncogenes, tumor suppressor
genes and DNA mismatch repair genes are the focus of DNA-based biomarker
approaches
- Epigenetic biomarker have the potential to guide treatment decisions
for a number of marketed and developmental agents
- Viral biomarkers have clinical potential for predicting treatment
response and prognosis following the diagnosis of virally-mediated
tumors.
- Mitochondrial DNA analysis has huge potential
- Pattern-based RNA expression analysis has been demonstrated in a
number of tumor types
- Commercial potential of RNA-expression arrays demonstrated by
Genomic Health's Oncotype DX
- Predictive expression profiles also exist for diffuse large B-cell
non-Hodgkins lymphoma
- Advances in gene expression profiling need to be matched by
improvements in patient outcomes
- microRNA approaches offer a novel approach to molecular profiling
- But challenges still cloud the path to the commerciazation of novel
RNA-based biomarker approaches
- CHAPTER 5 REGULATORY ISSUES PROVIDE CHALLENGES TO CANCER BIOMARKER
DEVELOPMENT
- Regulatory procedures for cancer biomarkers can be onerous
- Anylate-specific reagent designation facilitates laboratory use of
novel biomarkers but prohibits payer reimbursement
- Case study of Affymetrix-Roche's AmpliChip illustrates impact of
regulatory hurdles
- Industry guidance on pharmacogenomics aims to build expertise and
foundation for developing scientifically sound regulatory policies
- Ambiguities and developer concerns persist despite guidance
- New drug test co-development guidance aims to change existing paradigms
- Scientific, business and regulatory challenges hinder drug-diagnostic
co-launches
- Drug-test co-development concept paper focuses on technical/analytical
issues rather than clinical aspects
- Drug-test co-development may ultimately be a mandatory rather than an
elective path for developers to follow
- CHAPTER 6 BENEFITS AND RISKS OF PURSUING INCREASED MARKET SEGMENTATION
- Risk of increased market segmentation in the era of 'personalized
medicine' countered by need for developers to demonstrate cost-effectiveness
of new high-cost treatments
- Case study of HER-2/neu testing illustrates potential commercial
rewards of biomarker testing
- Fragmentation of cancer staging sytems may limit their clinical utility
- Industry anxiety related to relabelling of existing drugs
- But could the availability of epidermal growth factor receptor
mutational analysis have mitigated the failure of AstraZeneca's Iressa?
- Pharmacoeconomic challenges to the implementation of biomarkers
- CHAPTER 7 APPENDIX
- Bibliography
- Research methodology
- About Datamonitor
- About Datamonitor Healthcare
- Datamonitor Healthcare's research and analysis methodologies
- Datamonitor Healthcare's therapy area capabilities
- About the Oncology analysis team
- Key therapy team members
- Nish Saini, Lead Oncology Analyst
- Disclaimer
- List of Tables
- Table 1: Prognostic and predictive biomarkers used in oncology
- Table 2: NIH-FDA classification of biomarkers
- Table 3: FDA-approved cancer biomarkers
- Table 4: Biomarkers to guide prognosis and treatment decisions
- Table 5: Selected FDA-approved biomarker assays, test systems and kits
for BTA, CEA, CA125 and CA27.19
- Table 6: Medical imaging techniques in oncology
- Table 7: DNA-based biomarkers
- Table 8: Viral biomarkers in oncology
- Table 9: Prognostic and predictive utility of RNA-expression analysis
- Table 10: Selected HER-2 tests available in the US
- Table 11: Crude incidence rates of female breast cancer (per 100,000)
in the seven major markets, 2006
- Table 12: Female breast cancer incidence forecast in the seven major
markets, 2002-16
- Table 13: Forecast sales of HER2/neu testing (FISH alone) in the 7
major pharmaceutical markets 2006-2016
- Table 14: Forecast sales of HER2/neu testing (IHC followed by FISH in
IHC positive patients) in the 7 major pharmaceutical markets, 2006-2016
- List of Figures
- Figure 1: Prognostic biomarkers
- Figure 2: Predictive biomarkers
- Figure 3: Development of biomarkers for clinical use
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