Personalized Medicine: Its Coming Impact on the Health Care System

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Personalized Medicine Its Coming Impact on the
Health Care System

• Kathryn A. Phillips
• Professor of Health Economics Health Services
  Research
• UCSF

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Uses of Genetic Information
Uses of Genetic Information
Development of gene therapy
Genetic testing for risk stratification
Use of genetic information for treatment
decisions drug development
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What is Personalized Medicine?

• Targeting healthcare based on genomic information
  (Genetically-enabled healthcare)
• Stratified medicine
• Includes targeting of drugs (pharmacogenomics)
  targeted therapies (drugs based on molecular
  targets)
• Not individualized
• Genomics inherited (germline) acquired
  (somatic) mutations

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Will our new knowledge of genomics
revolutionize health care?

• Increased understanding of genomics raises hopes
  that health care can become more personalized
• Hope that personalized medicine
• can improve quality decrease costs

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Or is there a train wreck coming?
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Revolution or Train Wreck?

• In 20 years we will have predictive,
  personalized, preemptive health care
• NIH Director Zerhouni
• Hype? YES BUT - inevitable trend towards greater
  stratification targeting
• Knowledge of human genomics
• Emphasis on safety
• High drug costs
• Regardless of whether hype or not
• Inevitable that will change landscape
• of health care

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The Train Has Left The Station

• Many genetic tests targeted drugs available or
  coming
• 1700 clinics/labs using genetic tests for 1500
  diseases
• 70 tests under consideration for review by
  national advisory committee (EGAPP)
• Most activity in oncology but more coming in CHD,
  asthma, diabetes, mental health, AIDS
• W/in cancer, over 62 tests available 104 in
  development (as of 07)

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The Train Has Left the Station

• Historically, genetic testing has been used more
  frequently for prenatal/postnatal diagnosis
  rare, highly penetrant genes, e.g., BRCA 1/2
  (breast cancer), HNPCC (colorectal cancer)
• But personalized medicine is being or could be
  used in clinical practice increasingly for common
  and/or chronic diseases

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The Train Has Left The Station

• Cancer
• HER2/neu testing for trastuzumab (Herceptin)
• Gene expression profiling for cancer (Oncotype)
• CYP2D6 testing for tamixofen
• TPMT testing for leukemia, etc
• UGT1A1 testing for irinotecan (Camptosar)
• Coronary heart disease
• CYP2C9 VKOR testing for coumadin (Warfarin)
• Beta1-adrenergic receptor testing for
  beta-blockers (bucindolol)
• Psychiatric illness
• CYP2D6 testing for SSRIs
• AIDS
• HLA-B5701 screening for abacavir

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The Train Has Left the Station

• Industry using PGx data for drug development
• FDA pursuing initiatives to promote PGx
• Payers looking for approaches to better target
  interventions and PM offers hope
• Government looking to PM to provide better care
  at lower cost

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Challenges/Opportunities for Personalized Medicine

• Shifting Industry Paradigms
• Determining Value Reimbursement

• Balancing Innovation Regulation
• Building an Evidence Base

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Example of Genetic Test that Could Have Impact
on Health Care

• 25 all prescribed drugs metabolized by CYP2D6
  enzymes
• Antidepressants, beta blockers, pain relievers
• E.g., Prozac, Tamixofen, Claritan, Inderal,
  Codeine, Vicodin
• Potentially 189M scrips 12.8B
  expenditures/annually in US could be impacted
• Phillips et al, Nature Reviews Drug Discovery,
  2005

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Why Get Tested?

• If poor metabolizer risk adverse reaction
  (cant inactivate drug)
• If ultrarapid metabolizer risk no effect
  (cant activate drug)
• Prevalence varies widely by racial group
• 10 of Caucasians are PMs
• 10 of Hispanics (Mexican origin) are PMs 10
  UMs
• Readily available test (250 DTC)

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How Does CYP2D6 Testing Illustrate Challenges to
Health Care System
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Were Not in Kansas Anymore

• Diagnostic industry historically secondary to
  pharma industry but now more important role
• Is personalized medicine different?
• Should evidence threshold be similar to drugs or
  diagnostics?
• Should RCTs be required?
• Diagnostics such as CYP2D6 test can get lost
• Black box little data available compared to
  drugs
• Diagnostic/drug combos require integration of
  historically divided industries regulatory
  mechanisms

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A Tough Balancing Act

• FDA must balance regulation innovation
• Balancing needs
• Promoting personalized medicine
• Greater stringency to protect safety
• Industry innovation
• How should value be defined and by whom?
• Who should drive appropriate adoption? FDA? CMS?
  Private payers? Professional groups? Government
  agencies?
• Does CYP2D6 testing require full FDA approval?
• Is CYP2D6 testing screening or diagnosis?

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Wheres The Beef

• Often limited evidence of clinical utility
• Often limited evidence on public health impact
• Not enough known about CYP2D6s contribution to
  drug response
• Impact on SSRI use unclear
• One known death of newborn due to mother being an
  ultrarapid metabolizer of codeine
• FDA issued warning requested label change
• Minimal reporting in mass media little
  discussion of genetic testing
• How to balance individual vs. societal
  perspectives?

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And Whos Buying Lunch..

• Payers are taking notice because of huge need to
  reduce drug costs
• CYP2D6 is being used but not as hoped
• Used to screen out drugs in development
• Not reimbursed
• Lack of evidence
• Example of where everyone benefits so no one
  wants to pay
• Compare to gene expression profiling test for
  breast cancer
• Oncotype industry darling because high value
  diagnostic that has achieved reimbursement
  (3500)

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In Conclusion

• Where are we now?
• Not a revolution or train wreck
• Few success stories but many products in
  pipeline
• Where are we going?
• Inevitable trend towards greater personalization
• Potential to improve quality decrease costs
  but can it be realized?
• Theres a wonderful rule of thumb for American
  health care
• Shift happens
• Uwe Reinhardt