Transcript Nanotechnology Strategic Plan

Genetics and Genomics in Clinical
Medicine
Raju Kucherlapati, Ph.D.
Harvard Medical School
Partners Healthcare
Healthcare Issues
Healthcare costs are rising
rapidly
Costs of drug development at all
time high
Estimated cost of a new drug
800 MM
Drugs are not effective in all
patients
Some cancer drugs are
effective in less than 20% of
patients
Drug related adverse events are a
major cause of ER visits
Even when drugs are effective
severe adverse reactions can
cause major problems
GENETICS AND GENOMICS CAN
HELP
National Thought Leaders on Personalized
Medicine
“I believe we are moving
into a remarkable and
powerful new era in
medicine and particularly
in prescription drugs. I’d
refer to it as an era of
personalized medicine.”
Michael Leavitt,
Secretary HHS
January 18, 2005
What is Personalized Medicine?
The right drug or treatment, at the right
time, for the right patient, at the right
cost everytime
Personalized medicine requires genetic
or other type of testing
How fast the test results are available
becomes critical
Future of Medical Care
• A revolution in medical practice and care has to take place
• Personalized Medicine is a part of this revolution
• Some would consider the notion of Personalized Medicine to be
similar to many earlier disruptive technologies such as color
television and personal computers
• Implementation of Personalized Medicine would require
changes in many paradigms that include
• More discoveries
• Effectiveness
• Support of Regulatory agencies
• Positive cost/benefit ratio
• Rapid test results
• Physician and Public Education
• Effective IT support to manage and interpret results
Discoveries are becoming more rapid
August 2007
Genome-Wide Association Analysis
Identifies Loci for Type 2 Diabetes and
Triglyceride Levels
Diabetes Genetics Initiative of Broad
Institute of Harvard and MIT, Lund
University, and Novartis Institutes of
BioMedical Research et al
Effectiveness
Effectiveness can be measured by clinical data
Retrospective studies
Prospective clinical trials
Examples of a prospective clinical trails
For new drugs – Herceptin, Gleevec
For approved drugs - Warfarin
Genetics of Warfarin dosing
More than 20 million prescriptions of Warfarin every year and 2 million new
patients/year are prescribed Warfarin. It is the most effective oral anticoagulant
drug
Warfarin anticoagulation is prescribed to achieve a target INR. Excessive dosing
precipitates hemorrhage. Inadequate dosing predisposes to stroke and
pulmonary embolism. Dosing nomograms work poorly. Trial and error
predominates.
CYP 2C9
Genotype
*1/*1
Dose
7.2 mg
VKORC1
Haplotype
A/A
Dose
2.7 mg
*1/*2
*1/*3
4.1 mg
A/B
4.9 mg
*2/*2
*2/*3
*3/*3
1.4 mg
B/B
6.2 mg
We are now conducting a clinical trial to test the hypothesis
Regulatory Activity
August 16, 2007
PERSONAL DOSE
In Milestone, FDA Pushes
Genetic Tests Tied to Drug
Agency Seeks to Tame
Risks of Blood Thinner;
Some Doctors Protest
By ANNA WILDE MATHEWS
August 16, 2007; Page A1
FDA Approves Label Change for Warfarin
FDA Approves Genetic Testing Labeling For
Blood-thinning Drug
August 18, 2007
"Today's approved labeling change is one step in our
commitment to personalized medicine. By using
modern science to get the right drug in the right dose
for the right patient, FDA will further enhance the
safety and effectiveness of the medicines Americans
depend on,"
Andrew C. von Eschenbach, M.D.
Commissioner of FDA
Cost/Benefit Analysis for Warfarin testing
“We estimate that formally integrating genetic testing
into routine warfarin therapy could allow American
warfarin users to avoid 85,000 serious bleeding events
and 17,000 strokes annually. We estimate the reduced
health care spending from integrating genetic testing
into warfarin therapy to be $1.1 billion annually, with a
range of about $100 million to $2 billion.”
Andrew McWilliam, Randall Lutter and Clark Nardinelli
Office of Policy and Planning at the FDA
AEI-BROOKINGS JOINT CENTER FOR REGULATORY
STUDIES November 2006
Time to Getting Test Results
For Warfarin testing turn around times are 7-10 days
Too late for clinical dosing decisions
Need to have answers within 24 hours, preferably a few
hours
Ideal situation is POC diagnostic or a local lab that
provides results fast
Need to get the result into the electronic medical
record
Need to provide a dosing recommendation
We now provide Warfarin test results within 24 hours
Genetic data in EMR
Test Results in EMR
First Genetics Based Clinical Decision Support Rule
The Ultimate Goal
Personalized
Healthcare
Clinical data
Genetic variation
Megabytes – Gigabytes
of Data Per Patient
Genetic expression
The patient has disease X, subclass Y,
which will likely respond to drug Z
Proteomic expression