2013-04-17: The Promise, Current State, And Future of Personalized Medicine

The promise, current state, and future of personalized medicine

Jeffrey M. Otto, PhD MBA National Director, CHI’s Center for Translational Research

April 17, 2013

Overview

§  Intro to personalized medicine §  Short look at the early days, circa

2000-2001 §  Review of current state §  Discussion of the gap between the initial

promise and the current state §  The CTR’s approach §  Summary and conclusion

Definitions

§  Personalized medicine: the tailoring of medical treatment to the individual characteristics of each patient in order to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment.  Preventative or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.

§  Biomarkers: An indicator or pattern in a patient that reflects normal biologic processes, disease processes, or the effect of medical treatment.

§  Translational Research: Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce disease incidence, morbidity, and mortality.

Personalized Medicine 101

The Promise §  Better diagnoses and earlier interventions §  More efficient drug development §  More effective therapies The Challenges §  Intellectual property §  Regulatory oversight §  Reimbursement Retrieved 03/28/2013 from http://www.personalizedmedicinecoalition.org/about/about-personalized-medicine

The Classic Personalized Medicine Paradigm

Toxic   Not  Toxic  

Effec%ve  

Not  Effec%ve  

The standard approach to medicine does not distinguish between individuals….

…although individuals within a population are often very different.

Biomarkers can be used to stratify patients… …and to select a safer, more efficacious treatment for the individual.

Personalized medicine is akin to shoe manufacturing:

Like shoes at a department store, many different drugs are available. Although several drugs may be available to treat a particular disease, all drugs are not safe or effective for all people.

Similar to sizing for a shoe, molecular diagnostic tests inform the selection of the appropriate drug.

Although the selected drug was not created specifically for you, it is more likely to work for you.

Biomarkers currently used in clinical medicine

§  Electrocardiogram §  PET brain image §  Bone densitometric

measurement §  Serum chemistries

§  Auto-antigens in blood §  Pulmonary function test §  X-ray §  MRI

Examples of -Omic Biomarkers

§  DNA variation q  SNPs, rearrangements,

CNVs §  DNA methylation §  Chromosomal

rearrangements §  microRNA §  RNA expression §  Protein panels

The beginning of “irrational exuberance” in personalized medicine

June  11,  2001    "We  strongly  believe  that  pharmacogenomics  will  shortly  transform  the  way  drugs  are  developed,  marketed,  and  prescribed.  I  think  you're  going  to  see  the  benefits  of  this  appearing  within  a  five-­‐year  %meframe,"    

 Gerald  F.  Vovis    SVP  &  Chief  Technology  Officer  of  Genaissance  Pharmaceu%cals  

The Challenge of “chasing the tail”

§  Statistically significant results are easier to achieve between populations at the left and right ends of the diagram, but are not necessarily meaningful from a health economics perspective

Treatment efficacy

Freq

uenc

y in

pop

ulat

ion

Genomic medicine milestones

1953:  Structure  of  DNA  elucidated  by  Watson  &  Crick  

1950 1960

1956:  1st  discovery  of  a  gene%c  basis  for  selec%ve  toxicity  (primaquine  –  an%malarial  drug)  

1970

1977:  DNA  sequencing  technology  developed  by  Fred  Sanger  

1977:  Discovery  of  CYP450  metabolic  enzymes  -­‐  varia%on  in  these  enzymes  significantly  influence  the  effec%ve  dose  of  a  drug  

1980

1994:  EGFR  TKI  class  discovered  

1990

1990:  The  Human  Genome  Project  is  launched  

2000 2010

1998:  Hercep%n  approved  by  FDA  for  HER2+  metasta%c  breast  cancer  

1998:  1st  CDx  developed  by  Dako  –  Hercep-­‐Test    

2003:  The  Human  Genome  Project  is  completed  

2004:  Targeted  therapies  approved  in  colorectal  and  NSC  lung  cancer  

2007:  FDA  updated  Coumadin  label  to  recommend  gene%c  tes%ng  for  dosage  administra%on  

2011:  1st  simultaneous  approval  for  drug  (Zelboraf)  &  CDx  for  melanoma  with  BRAF  V600E  muta%on  

2011:  Simultaneous  approval  for  Xalkori  &  CDx  for  NSCLC  with  abnormal  ALK  gene  

Milestones  Research  

Drugs  

Diagnos?c  

Drug  +  CDx  

Regulatory  

Milestones  Research  

Drugs  

Diagnos?c  

Drug  +  CDx  

Regulatory  

Overview of Targeted Cancer Therapies

Manchana, T., Ittiwut, C., Mutirangura, A., & Kavanagh, J. J. (2010). Targeted therapies for rare gynaecological cancers. Lancet Oncol, 11(7), 685-693. doi: http://dx.doi.org/10.1016/S1470-2045(09)70368-7

Why so few success stories?

§  Genomic era of medicine is less than 15 yrs old

§  Technology is not sufficient on its own

§  Biomarkers are not necessarily “fit for purpose”

§  Test needs to work within the existing healthcare workflow

§  Stakeholder alignment §  Is the patient the customer?

Cartoon: Agres, Ted. (2009) The hunt for personalization. Retrieved 03/08/2013 from http://www.dddmag.com/articles/2009/06/hunt-personalization

Catholic Health Initiatives & The Center for Translational Research

CHI: 5th Largest Hospital Network in US

Strength in Numbers §  5th largest US network §  81 acute care hospitals in 17 states §  40 LTC facilities §  86,000 employees §  2,900 physicians and midlevel providers §  Diverse markets with 90% ranked #1 or #2 §  $15B in assets, $9.8B in annual revenue §  FY 2012 – provided $715M+ in charity care

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CIRI Overview

Center  for  Transla%onal  Research  (CTR)  • Discovery  Research  Network  na%onal  biospecimen    collec%on  &  repository  with  EHR  connec%vity  

• Biomarker  discovery,  molecular  diagnos%c  development  &  valida%on    

Center  for  Clinical  Research  (CCR)  • Ownership  and  management  of  • Research/clinical  trial  opera%ons:  single  site,  mul%-­‐site,  mul%-­‐therapeu%c    

• Research  data  warehouse  connected  to  EHR  and  de-­‐iden%fied  pa%ent  data/outcomes    

Center  for  Healthcare  Innova%on  (CHCI)  • Design  and  test  innova%ons  in  care  delivery  

• Co-­‐develop  new  technology  and  methods  to  manage  popula%on  health  

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Personalized  Medicine  

Clinical  Opera%ons  +  EHR  Research  Environment  

Popula%on  Health  Management  

Executive Summary: The CHI/CIRI Research “Onion”

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CCR  

CTR  

CHCI  

CIRI  Hospitals  

Government  

Academia  

Industry  Lab  

Pharmacy  

Radiology  

Tumor  Registry  

Pathology  

Cloud-based Informatics: Network Strength

Research  Datamart  

CCR   CTR  

Research  Data  

Analysis  

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Cloud-based informatics: Patient Data & Sample Annotation

Hospita

l  Network  

Digital  Slide  Images  (QC)  Staging  –  pTNM,  cTNM  

Images  Radiology  Reports  

Genomic  Data  Blood  Report  

Demographics  Clinical  History  Epidemiology  

Drugs  Interac%ons/Adverse  Events  

Consent  &  IRB  Approval  

Pre-­‐Sampling  Ischemic  dura%on    Chain  of  Custody  

Anesthesia  

outcomes  

Lab  

Radiology  

ADT*  

Tumor  Registry  

Pharmacy  

Pathology  

Post-­‐Sampling  Time  to  freeze  samples  

Type  and  %me  of  fixa%ve  Tissue  QC  

ELECTRONIC  HEALTH  RECORD   BIOREPOSITORY  NETWORK  

Drug  and  Biomarker  Discovery  

Protocol  

De-Identified Data Warehouse

Biospecimen Variables

Tissue Report

Anesthesia Ischemic Time Time to Freeze

Tumor Staging Diagnosis % Tumor

% Necrosis

Image Data Demographics

MRI PET/CT Scan Image Report

Age Race

Gene Expression Profiling

Genotype/ Sequence Data

Affy Human Genome Expression Array

EGFR KRAS

Follow Up Data Treatment

Treatment Outcome Recurrence

Disease Status

Drugs Radiation Response

Pre-­‐Acquisi%on  Variables  

Post-­‐Acquisi%on  Variables  

*Admission/Discharge/Transfer  

TRANSLATIONAL  INFORMATICS  

Bench to Bedside Translational Research

CTR  

CCR  

Benefits  to  CHI  Hospitals  

Clinical  Trials  

Personalized  Medicine  

Benefits  to  Pa%ents  

Bener  Drugs  

Bener  Diagnos%cs  

Research  Ques?ons  

Hypothesis  Generated  

Hypothesis  Tested  

Results:    IP  &  

Publica?ons  Generated  

Benefits  

Research  Data  

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Key  Opinion  Leaders  

Physicians  

Academic  Researchers  

CIRI  Staff  

Others  

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Study Design: An Integrated Approach

FFPE  Sample  

EHR  data  

Biosta%s%cal  Analysis  

Predic%ve  Signature  

Gene%c  

Epigene%c  

Environmental  

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Thank You