Transforming Healthcare Delivery: Leveraging Genetic/Genomic Technologies

Brad Popovich, CSO 13th Annual Western Canadian Healthcare Summit

June 25, 2013 / Kelowna, BC

Presentation goals

• Allow you to understand the difference between genetics and genomics

• Why genetic/genomic testing has become a standard of care diagnostic test for a wide variety of diseases

• The transformative impact of genomic “technology” development in healthcare

• Connect genomic and personalized medicine

• Provide a 5 year vision of what to realistically expect from genomics in the healthcare setting

• Provide an understanding of Genome BC’s role in the delivery of the above

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• A catalyst for the life sciences cluster on Canada's West Coast

• Cumulative portfolio of over $625M in 180 genomics research projects and science and technology

• Focusing on sectors of economic importance to BC and Canada: • Agriculture

• Aquaculture & Fisheries

• Forestry

• Mining, Energy & Environment

• Human health

• To generate social and economic benefits

Genome British Columbia

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Background

• Co-founded by the late Dr. Michael Smith, Nobel Nobel Laureate, Genome British Columbia was formed in July 2000

• The initial strategic plan covered the period 2001 through 2005, with a $69M program

• Genome BC has successfully implemented its second strategic plan (2005-2010) and exceeded the $300M research program

• Genome BC has initiated its third strategic plan (2010-2015) and plans a $340M research program

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Investment Sources

International, Industry &

Institutional 30%

Provincial 25%

Federal 45%

Research Investment Objectives

• Match BC’s key economic concerns.

• Leverage contributions from other organizations.

• Maintain partnerships with a broad cross-section of provincial institutions, and locations.

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“Understanding a disease from the inside out”

• If you know the genetic or genomic cause of a disease you understand the cause of the disease

• Contrast this to looking at symptoms

• This genetic / genomic information is beneficial for disease

• Diagnosis

• Management

• Therapeutic management

• Family planning

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Genetic - Genomic Medicine Continuum

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Genetic Disease

• Genetic diseases are caused by defects (i.e. mutations) in single genes

• 25K genes in our genome

• Approximately 6,500 genetic diseases

• Approximately 1,500 genetic diseases can be diagnosed by genetic testing

• Examples include both pediatric and adult diseases:

• Cystic fibrosis

• Muscular dystrophy

• Huntington’s Disease

• A single gene can have thousands of different defects

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RARE DISEASES ARE COMMON

• 5-10% of the population may have a genetic condition, many undiagnosed

• 1 in 500-1,000 has a cardiomyopathy, Cardiomyopathy.org

• 1 in 2,000 has Long QT Syndrome, Circulation 120:1761, 2009

• 100% of the population is carrying multiple rare genetic conditions

- Every individual carries multiple (50-100?) mutations that disrupt protein function MacArthur et al. Science: Feb 17, 2012 335: 823-828

• 100% of the population carries genetic variation that effects their response to certain drugs

• A significant effect on efficacy and adverse events JAMA 286:2270, 2001

• Every “common” disease is either caused or effected by genetic differences

- Most of which is not yet known Nature Genetics 33:177, 2003

Genomic Disease

Genomic diseases are caused by mutations in more than one gene

• Cancer is a genomic disease

• Some cancer mutations may be inherited

• Many chronic diseases are genomic

• A mix of our inheritance and our environment

• Many cancers look identical at the patient/symptom level but they have distinct and different genomic causes

• The distinct genomic “signature” present in a person’s cancer hold the key to improved therapeutic outcomes

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Genomics is the “fuel” of Personalized Medicine

• Allows the “stratification” of disease that appear identical

• Stratification leads to improved outcomes: examples

• Cancer

• Breast/HER2

• Ocotype Dx

• CML/Gleevec

• Cystic fibrosis

• HIV

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Genomic Medicine = Personalized Medicine Pertinent to all areas of medicine

• Oncology

• Microbiology

• Pharmacology

• Neonatology

• Perinatology

• Emergency medicine

• Public Health

• Neurology

• Newborn screening

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Personalized Medicine Spectrum of Genetic/Genomic Contribution to Disease

Very rare single gene disorders

More common single gene disorders • Cystic Fibrosis • Hemophilia • Huntington’s Disease • Muscular Dystrophy

Disorders with prominent genetic contribution • Childhood cancer • BRCA 1/2 Breast cancer • Some forms of autism

spectrum disorders • Adverse drug reactions

Genetic susceptibility to certain common diseases • Colon cancer • Certain cardiovascular diseases • Certain forms of Alzheimer

Most common chronic diseases with many genetic factors but also major environmental factors contributing to disease onset

Personalized Medicine : a New Paradigm

“One-size-fits-all” paradigm:

Same frequency of testing for large population (e.g. mammograms)

Symptom-driven diagnosis

Therapy based on clinical symptoms

Monitoring based on clinical symptoms

Personalized medicine paradigm:

Test for markers that ↑ risk (e.g.

genetic variants in cancer)

Focused prevention efforts in people with ↑

risk

Focused monitoring in

people with ↑ risk

Molecular monitoring for

disease subtypes

Targeted therapy based on disease subtype, risk of

adverse response

Molecular monitoring for

response to therapy

Source: Personalized Medicine Coalition

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Support for Personalized Medicine in British Columbia

Personalized Medicine Program (Genome BC)

• investigator-driven

• outcomes are ready for clinic use and/or uptake into the health system within 3 years of launch

• Must demonstrate the support from the payer (e.g. a regional health authority) & the potential cost-effectiveness of the translation of the proposed research to the healthcare system

• project budget up to $3 million

Genomics and Personalized Health (Genome Canada)

• in partnership with Canadian Institutes of Health Research (CIHR),

• deliverables clinical utility and/or practical applicability

• project budget $10 million

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Genomics Applied to the Management of High-risk AML/Myelodysplastic syndromes – Karsan and Marra ($3.0M) (BC Cancer Agency, BC Cancer Foundation)

Primary Research Objective

• Develop a genome-wide sequencing assay of RNA and/or DNA on a next-generation sequencing platform and ensure that all the known mutations that predict outcome of AML treatment are identified in a cost-effective manner

Implementation of a Pharmacogenetic ADR Prevention Program in BC – Hayden and Carleton ($4.0M) (Children’s and Women’s Health Centre and UBC; co-funding partners include Merck, IBM, Pfizer over two projects)

Primary Research Objective

• Demonstrate the utility and cost-effectiveness of pharmacogenetic tests designed to prevent cisplatin-induced deafness and anthracycline-induced heart failure

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Clinical Implementation of Diagnostic Biomarker Assays in Heart and Kidney Transplantation – McManus et al ($2.6M) (St. Paul’s Hospital, Vancouver Coastal Heath, and UBC)

Primary Research Objective

• To develop simple, safe, accurate, and cost-effective diagnostic tools that improve transplant patient outcomes and reduce costs

Stratifying and Targeting Pediatric Meduloblastoma Through Genomics - Marra ($9.9M) (Hospital for Sick Children, Genome Canada, Terry Fox Research Institute, Ontario Institute for Cancer Research et al.)

Primary Research Objective

• To develop markers that will more accurately classify the Meduloblastoma, the most common form of childhood brain cancer, to optimize treatments to improve the quality of life of patients. 17

Genomics and Personalized Health – New Projects

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Project Leader(s) Project Title Total

budget

Joseph Connors Marco Marra Randy Gascoyne

Personalized Treatment of Lymphoid Cancer: British Columbia as Model Province $10M

Richard Harrigan Julio Montaner

Viral and Human Genetic Predictors of Response to HIV Therapies $4.9M

Andrew Penn Christoph Borchers Shelagh Coutts

Reducing Stroke Burden with Hospital-Ready Biomarker Test for Rapid TIA Triage $9.8M

Don Sin Raymond Ng

Clinical Implemetation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management

$7.2M

Viral and Human Genetic Predictors of Response to HIV Therapies – Harrigan and Montaner

Primary Research Objective

• Optimize HIV therapy, improve HIV suppression and reduce HIV drug resistance

Key Specific Objectives

1. Implement a multi-class HIV drug resistance test based on next-generation sequencing

2. Establish a program for real-time investigation of HIV resistance incidence and prevalence

3. Expand the current program of human pharmacogenetic testing (for abacavir) by validating additional human genomic tests to guide HIV therapy

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Reducing Stroke Burden with Hospital-Ready Biomarker Test for Rapid TIA Triage – Penn, Borchers, Coutts

Primary Research Objective

• Develop a quick, easy and inexpensive blood test that helps emergency room physicians triage patients with transient ischemic attacks (TIA) or TIA mimic conditions

Key Specific Objectives

1. Develop and validate a biomarker panel algorithm with high negative predictive value for TIA

2. Examine the incremental value of proteomic testing over clinical criteria, combine both in an algorithm embedded in an electronic triage referral tool (CarpeDiem), and migrate the biomarkers to a mass spectrometry bench-top assay

3. Examine barriers to dissemination of the CarpeDiem tool and inform its design

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Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management – Sin and

Ng

Primary Research Objective

• Develop and implement blood-based tests for diagnosis and prognosis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD)

Key Specific Objectives

1. Replicate and refine promising biomarkers for AECOPD prognosis, migrate biomarkers to a rapid turnaround time platform, and assess analytical and clinical validity and clinical utility

2. Replicate and refine promising biomarkers for AECOPD diagnosis, migrate biomarkers to a rapid turnaround time platform, and assess analytical and clinical validity and clinical utility

3. Develop and refine decision-analytic tools to model the impact of the tests on patients and on health systems, and work with guideline committees and family physician groups to ensure optimal physician uptake and utilization of these tests.

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Personalized Treatment of Lymphoid Cancer: British Columbia as Model Province – Connors, Marra, Gascoyne

Primary Research Objective

• Implement a system incorporating the high throughput sequencing and gene expression profiling into the basic diagnostic and treatment planning for lymphoid cancer

Key Specific Objectives

1. Build a province wide, dependable system to capture diagnostic biopsy material and report genomic profiling of selected lymphoid cancers to treating specialists

2. Build the capacity to provide real time genomic profiling of formalin fixed paraffin embedded tissue specimens; develop and validate standardized, informative, actionable reports to be delivered to the treating clinical specialists

3. Determine the improvement in outcome provided by genomic profiling, conduct robust analyses of cost-effectiveness, and develop economic models that facilitate sensitivity analyses to identify key drivers of savings and costs

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Science and Technology Innovation Centres: 2013-2015: Platforms

Genomics: Genome BC Genomics Innovation Centre at the BC Cancer Agency Genome Sciences Centre (Drs. Marra, Jones, and Holt)

• $8.7M

Proteomics: University of Victoria-Genome BC Proteomics Centre

(Dr. Borchers)

• $4.3M

Metabolomics: The Metabolomics Innovation Centre (Drs.

Wishart –University of Alberta and Borchers)

• $1.7M

Genomic Sequencing: Truly Disruptive

• Technology that has – over the past 10 years- decreased in cost by 1 million fold

• Is perturbing the status quo

• What can your genome tell you about your health status?

• What can it tell you about your future health?

• Who owns your genome data?

• Who has access to it?

• How will it be used?

Genomic Technology: Truly Disruptive

• Highlights the problematic quality of existing medical records

• Consumers will be the primary driver

• Decreased technology cost is leading to widespread accessibility to genetic/genomic content

• Physician, patient, and consumer access

• Genetic disease testing undergoing massive change

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Translation is a complex matter

• How good is the technology? (clinical validation)

• In a fast moving field, when do we decide that “now is the time for transfer”

• Do we adapt existing clinical laboratory structures?

• Who will be making these decisions? (and based on what criteria?)

• Technology assessment based on sound economics and clinical benefit?

• Who will pay?

• Who will benefit and who will lose?

Concluding Remarks

• The predicted price of genomic testing is decreasing at an annual rate of 30%

• We are quickly leaving a time of genomic scarcity and moving into a world of genomic abundance

• Patients will lead the charge

• What is causing their illness

• What may cause future illness

• What is pertinent to their family

For More Information: Website:

www.genomebc.ca

Contact:

THANK YOU!

Brad Popovich, Chief Scientific Officer, Genome BC

bpopovich@genomebc.ca

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