Transcript The CIO`s Perspective: Regulatory Compliance in Life Science

Life Science Insights Telebriefing
Molecular Biomarkers: The Elusive and Expensive
Search for Powerful Tools That Could Redefine
Drug Discovery and Development
February 24, 2005
Patricia L. Reilly, M.S., Research Manager
Alan Susser, Senior Consultant
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Agenda
 LSI Overview
 Situation Overview
 Biomarkers Defined
 Types of Biomarkers Being Used
 Current Biomarker Areas of Focus
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Pharma Challenges in Drug Discovery and Development
ROI Benefits for Utilizing Biomarkers
Use of Biomarkers in Development
Use of Multiple Biomarkers
Forecasted Investment in Biomarkers for 2004 - 2007
FDA Critical Path Initiative
Risks of Reporting Toxicogenomics Data
Conclusions
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Work closely with IDG and its life sciences publication, Bio-IT World
Staff comprised of life science specialized analysts, researchers & consultants
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Molecular Biomarkers Research Analysis
 Initial study sponsored by Applera and Abbott as
part of “Targeted Medicine” Scientific American
Conference in NYC last November
 Phone interviews with opinion leaders and researchers in
the field
 LSI research focuses on biomarkers as part of our
clinical trial research agenda
 Contact with industry leaders
 Following FDA Critical Path Initiative
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Molecular Biomarkers
FDA Definition:
A biomarker is a characteristic that can be objectively
measured as an indicator of normal biologic processes,
pathogenic processes or pharmacological responses to
therapeutic intervention.
Types of biomarkers currently used:
• Proteins: Applicable throughout the drug discovery and development
process; longest history as biomarkers
• RNA Expression Profiling: Gene arrays used in discovery phase and
clinical trials
• SNPs (Single Nucleotide Polymorphisms): Large patient populations
required has hindered use but should increase in the future
• Small Molecules: Used the least; may increase with the successful
application of metabonomics
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Current Biomarker Areas of Focus
• Efficacy: Reflects beneficial
result of treatment
• Mechanism: Reports the
downstream effect of drug
Mechanism
(22%)
Disease
(22%)
• Disease: Relates clinical
outcome or measure of
disease
Toxicity
(20%)
• Toxicity: Reports toxicological
effect of drug on in vitro and
in vivo systems
Staging
(8%)
• Staging: Distinguishes
between different stages
of disease
Efficacy
(28%)
n=17
Source: Life Science Insights/ Applera/ Abbott Biomarker Survey Nov 2004
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Pharma Challenges in Drug Discovery & Development
 Escalating Cost of Bringing Drugs to Market
 Estimates range from $800M to $1.7B
 Emergence of New and Expensive Technologies and Screening
Platforms
 Risk/Benefit decisions needed, e.g.which discoveries will most likely
succeed
 Estimated Drought Within Company Pipelines for New Drugs
 Drug development has not kept pace with new discoveries
 FDA has seen a dramatic decrease in the number of NDAs filed
 Increased Need to Partner/Acquire or In-License
 Competitive Positioning
 New Initiatives in a Post-Vioxx World
 New FDA Drug Safety Oversight Board to monitor safety of marketed drugs
 Public perception of prescription costs, safety issues
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ROI Benefits for Utilizing Biomarkers
 Throughout drug discovery and development value chain,
molecular biomarkers can play a key role in decision
making, most important is the ability to kill drugs earlier.
 Early Drug Discovery
 Elucidation of disease mechanism, target validation
 Determination of efficacy and toxicity in in vitro testing
 Preclinical Development
 Determination of efficacy and toxicity in in vivo testing
 Finding key relevant biomarkers to move into clinical testing phases
 Clinical Development
 Determination of efficacy and toxicity in man
 Potential for prospectively testing patients for entry into trials, reducing trial
size and drop out rates
 Monitoring outcomes of disease
 Providing better, safer therapies for patients
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Use of Biomarkers During Stages of Development
Early-Stage
Discovery
Pre-Clinical
Development
Clinical
Development
0
10
20
30
(%)
40
50
60
Source: Life Science Insights/ Applera/ Abbott Biomarker Survey Nov 2004
Multiple answers accepted, total >100% n=22
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Use of Multiple vs. Single Biomarkers
Multiple markers and panels (e.g., metabolites, genes, and proteins)
are considered of greater relevance to drug development than single
markers. Of those who stated that they are currently using single
markers, most shared the opinion that the future will focus on multiple
markers.
Single (38%)
Multiple (62%)
n=17 Source: Life Science Insights, Applera, and Abbott's Biomarker Survey, November 2004
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Multiple vs. Single Biomarkers
 The Future Is Panels of Markers
 Looking at single variants to assemble into panels as
they are characterized
 Using combinations of analytes -- e.g., combining 6
metabolites, 3 genes and 4 proteins into panel
 Development of core sets of markers
 Use of toxicogenomics, metabonomics and proteomics
will increase
 62% use panels now; others are moving in this direction
 As drugs move toward clinic, fewer “key” markers
desirable
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Forecasted Investment in Biomarkers for
2004 -2007
Key Drivers for Increased
Spending:
Decline (0%)
• Competitive industry trends
No change
• Need to implement past
investments
(23%)
• Growing awareness that toxicity
markers may be a regulatory
requirement for future filings
Increase (77%)
Same Spending:
• Have already heavily invested
• Need to examine where investments had produced results
• Examine what the path forward should look like
n=22 Source: Life Science Insights/ Applera/ Abbott Biomarker Survey Nov 2004
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Declining NDAs Filed
Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical
Products [online], <http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html> (2004)
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FDA Critical Path Initiative
Concern:
• One half of all drugs moving to Phase III fail to emerge as new therapeutics
• Drop in number of NDAs being filed
Goal:
• Move drugs more quickly and safely through clinical trials
• Increase the predictability of drug success
Potential for Biomarkers in Clinical Trials:
• Change the risk/benefit ratio for patients
• Reduce number of patients enrolled
• Enrich the population of patients who will benefit
• Reduce the likelihood of adverse events
FDA is establishing an Interdisciplinary Pharmacogenomics Review Group and a
pharmacogenomics advisory subcommittee to assess data and correlations between
biomarkers and clinical outcomes
FDA is encouraging submission of unvalidated biomarkers with filings
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Submission of Unvalidated Biomarker Data to FDA
Unsure
(10%)
Possibly
(5%)
Yes (56%)
No (29%)
Key Points:
• Still considerable resistance until regulatory issues are defined.
• Pharma and biotechs are aligned in their approach to voluntary
submission.
• Some want to be seen as leaders; some identify themselves as
conservative.
n=21
Source: Life Science Insights/ Applera/ Abbott Biomarker Survey Nov 2004
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Toxicogenomics: New Technology Still Evolving
Risks of Reporting Toxicogenomics Data to the FDA
We run the risk of
bad comparisons
(14%)
The risks are
minor (18%)
We would face
new liabilities
(16%)
The FDA would
reach a different
interpretation
(34%)
The FDA will
require us to do
more work (18%)
n = 35
Very few respondents felt comfortable submitting data
Source: Toxicogenomics: Current Industry Sentiment and Future Trends, Life Science Insights,
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Prerequisites for Toxicogenomics Data Submission to the FDA
Q. What advances would be necessary for your organization to submit toxicogenomics data to the FDA?
Better biology
Improved industry standards
Safe Harbor Agreement
Better FDA training
Validated biomarkers
We would never submit
unless required
0
10
20
30
40
50
(% of respondents)
60
70
N=35
Source: Toxicogenomics: Current Industry Sentiment and Future Trends, Life Science Insights
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Factors Preventing Wider Adoption of Biomarkers
 Factors preventing the wider adoption of biomarkers focused on two
areas -- internal and external problems:

Internal:
 The lack of a defined strategy to date
 The need for organizational communication and coordination across
departments
 The difficulty in identifying biomarkers
 The difficulty in finding the right balance of effort between the new
approaches and the more traditional approaches and then driving those
changes throughout the organization
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External:
 Regulatory climate and uncertainties of future FDA requirements
 The consequent impact on internal conflicts about whether companies want
to have information that they cannot explain
 No payback for the effort (due to the state of regulation and the state of the
industry)
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Key Market Trends and Drivers
 Drug companies will continue to increase biomarker investments
primarily focused at early discovery stage through Phase I/IIa
 Key drivers for increased biomarker investment include:
 Increased need in data integration and data mining tools for real-time use of
information during trial
 Ability to make earlier go/no go decisions
 Accelerated time to market
 Bringing safer and more efficacious products to patients
 In addition, companies are starting to voluntarily submit data to the FDA,
but some want more clarity on requirements
 Key trends include:
 Toxicology biomarkers will be regulated and required
 Single markers are seen as clinical ideal; however, companies will continue
to pursue panels of multiple markers.
 Firms will aggressively plan a strategy for companion diagnostics that may
include partnerships
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Key Takeaways
 Investment in biomarker research has dramatically grown and will continue to
grow as companies realize the potential for savings at all phases of drug
development.
 Systems biology and new technologies, including new nanotechnology
platforms, will continue to evolve, driving additional spending as novel
approaches move into the predictive and preventive medicine arena.
 Companies are alert that their competition is actively involved in the same
activities, and there is a recognized need for identification of validated
biomarkers.
 Investment payoff will be earlier go/no go decisions and quicker downstream
returns.
 Biomarkers will enable segmentation of patient populations during clinical
trials; hence, the clinical trials of the future will be smaller and safer.
© IDC, 2005
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Related Research

Toxicogenomics: Current Industry Sentiment and Future Trends
(IDC # 32687 , December 2004)

Worldwide Therapeutic RNAi 2004–2014 Forecast and Analysis
(IDC # 31941 , October 2004)

Proteomics: Protein Array Market and Technology Overview
(IDC # 31405 , June 2004)

Biodefense: Novel DNA Analysis Technologies for Next-Generation Early
Warning Biodetection Systems and Their IT Implications
(IDC # 31332 , May 2004)

The $1,000 Human Genome — Implications for Life Science, Healthcare, and IT
(IDC # 30968 , March 2004)

Whole-Genome Sequencing Has Gone to the Dogs
(IDC # 30343 , November 2003)
© IDC, 2005
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Questions?
Patty Reilly
Research Manager
508.988.7957
[email protected]
Alan Susser
Senior Consultant
212.696.8088
[email protected]
© IDC, 2005
lifescience-insights.com