Emerging and New Technologies

• Debra G.B. Leonard, MD, PhD, FCAP, Weill Cornell Medical College, New York Presbyterian Hospital

• Patricia Deverka, MD, MS, MBE, Center for Medical Technology Policy

Debra G.B. Leonard, MD, PhD, FCAP

Pathologists and Genomic Medicine

May 8, 2012

Objectives

• Pathologists have an opportunity to lead in Genomic Medicine and why this is important

• Today’s challenges to widespread adoption of Genomic Medicine

• How Genomic Medicine affects all pathologists

• The College’s Advocacy efforts to support pathologists in Genomic Medicine

Understanding of the Human Genome Combined with Sequencing Technology Advances are Moving Us Toward Genomic Medicine

Human Genome ProjectCompleted 2003

Human Genome ProjectCompleted 2003 1 Generic Genome1 Generic Genome

Direct Patient CareDirect Patient Care

Improve OutcomesImprove Outcomes

Genomic Medicine is made possible by ability to analyze individual patient genomes

Genomic Medicine is made possible by ability to analyze individual patient genomes

Genomic Medicine(Personalized

Medicine)

Genomic Medicine(Personalized

Medicine)

Individual Patient Genomes

Individual Patient Genomes

Technology & Knowledge Advances

A Cancer Genomics Case: Diagnosis & Treatment

(Jones et al. Genome Biology 2010, 11:R82)

• 78 yr. old Caucasian male with base of tongue mass

• Mass resected, followed by adjuvant radiation• 1.5 cm poorly differentiated adenocarcinoma with

micropapillary & mucinous features; • 3/21 neck LNs positive;• 2+ EGFR IHC staining

• Lung nodules developed• Tx: Erlotinib (EGFR inhibitor)• Continued growth on therapy

• Consent for genome & transcriptome analysis of lung nodule biopsy

A Cancer Genomic Case: Genomic-Based Treatment

• RB1 & PTEN loss associated with EGFR inhibitor (gefitinib) resistance c/w erlotinib failure

• Up regulation of RET and RET signaling pathway

• Treated with sunitinib (RET inhibitor) with lung nodule reduction & stable disease for 4 months

• Switched to a multi-kinase inhibitor (sorafenib) with stable disease for 3 months

• Repeat genomic analysis of met suggested need for combination treatment with RET, EGFR and mTOR inhibitor therapy; not done

(Jones et al. Genome Biology 2010, 11:R82)

Genomic Analysis has the potential to individualize treatment for each cancer to

improve response

Genomic Analysis has the potential to individualize treatment for each cancer to

improve response

Genomic Medicine is Driving a Strong Global Molecular Diagnostics Market with Estimated Annual Growth Rate of 13.6%

World Market for Molecular Diagnostics, 2009-2015E

Source: ‘Valuation of Carried Intangible Assets’, Acuity Technology Management, June 2011

CAGR

13.6%

Genetics & Oncology Show Highest Growth with Continued Growth in Infectious Diseases

US

D M

M

1,282

1,444(13%)

1,628(13%)

1,839(13%)

2,080(13%)

2,354(13%)

2,667(13%)

Source: ‘Valuation of Carried Intangible Assets’, Acuity Technology Management, June 2011; The Future Of Molecular Diagnostics: Innovative technologies driving market opportunities in personalized medicine. Business Insights report No: BI00021-012. 23 June 2010.

North American Genetic, Oncology and Infectious Disease Market, 2009–2015E

Genomic Analysis by Next Generation Sequencing is Being Used in Molecular Pathology Practice Today

Next Generation Sequencing is the newest Molecular Pathology technology and is being used now

Next Generation Sequencing is the newest Molecular Pathology technology and is being used now

Single Gene/Pathogen

Few Genes/Pathogens

Single/Few Mutations

Past and Continuing Molecular

Pathology TestsGene Panels

Exome

Genomic Analysis:Clinically Useful

Now

Transcriptome

Genome

Genomic Analysis: Research & Future

Potential

= Genomic Analysis by Next Gen Sequencing

Research will increase clinical use

Some Molecular Pathology Tests Will Move to Next Generation Sequencing While Others Will Remain on Current Platforms

Current Molecular Pathology Testing

Examples

Current Molecular Pathology Testing

Examples

Molecular PathologyMolecular Pathology

• Viral Loads

• Bone Marrow Engraftment Analysis

• Deafness Genetic Testing

• EGFR Mutations

• KRAS Mutations

• BRAF Mutations

Genomic AnalysisGenomic Analysis

• Cancer

• Specific inherited disorders

• Cancer

• Unidentified inherited disorders

Gene Panels Exome

Opportunities Exist for ALL Pathologists to Play Key Roles Within Genomic Medicine

All PathologistsAll Pathologists

All PathologistsAll Pathologists

Pre-AnalyticalPre-Analytical

Sequence Data InterpretationSequence Data Interpretation

Reporting & Billing Reporting & Billing

Clinical ConsultationClinical Consultation

Sequence Data Generation Sequence Data GenerationMolecular Pathologists, Molecular Geneticists, Industry & Others with

strong molecular biology or genetics knowledge

Molecular Pathologists, Molecular Geneticists, Industry & Others with

strong molecular biology or genetics knowledge

The Cost of Genome Sequencing Is Decreasing Rapidly and Driving Clinical Adoption of Genomic Analysis

Source: National Human Genome Research Institute

Cost per Genome Data Generation, 2001 – 2011

Cost for genome sequence data generation today is <$3,000

Cost for genome sequence data generation today is <$3,000

Early Adopters Identify Clinical Grade Databases and Bioinformatics Tools as a High Priority Need

• Clinical Database(s): oRequire significant time & moneyoNeed to define quality & submission standards oNeed to define access & IP issues

• Software Tools for Interpretation and Clinical Usefulness: oRequire significant time & money oMany software tools being developedoNo interoperability standardsoWill facilitate role for ALL pathologists in Genomic

MedicinePathologists should be at the table in the

development of bioinformatics tools & should learn to use tools as developed

Pathologists should be at the table in the development of bioinformatics tools & should learn

to use tools as developed

Opportunities Exist for ALL Pathologists to Play Key Roles Within Genomic Medicine

What is the landscape for ALL Pathologists in the Pre-Analytical & Clinical Consultation Phases for Genomic Testing?

Pre-AnalyticalPre-Analytical

Sequence Data InterpretationSequence Data Interpretation

Reporting & Billing Reporting & Billing

Clinical ConsultationClinical Consultation

Sequence Data Generation Sequence Data Generation

Clinical Decision Support Tools Can Assist ALL Pathologists with the Pre-analytical and Clinical Consultations for Genomic Medicine

Variant Database

Sequence Analysis

Clinical Decision Support

Source: Grail Analysis

Bioinformatics

Bioinformatics

• Need clinical quality databases and software tools• Pathologists must participate in development

Speed of Clinical Adoption Hinges on Several Factors

Decreasing Costs

Decreasing Costs

• Cost of genome analysis is rapidly decreasing • Sequencing instruments now are clinically affordable

• Genomic Analysis is in clinical use now (small but growing)

• Research/discovery will increase clinical applications

Clinical Usefulness

Clinical Usefulness

Payment Uncertainty

Payment Uncertainty

• Currently, no specific CPT codes exist for Genomic Analysis

• Payers do not understand Genomic Analysis

Increasing Speed

Increasing Speed

• Can generate sequencing data in 10-36 hours• Clinically relevant TAT available today for data

generation

Regulatory UncertaintyRegulatory Uncertainty

• Federal regulatory uncertainty today• Quality standards being led by CAP with AMP & ACMG

Current GA Reporting and Payment Environment is Uncertain

• No IT standards for reporting in LIS, EHR & PHR

• Interoperability standards

• Terminology standards• Molecular CPT Codes

under revision• No GA CPT Codes available• Payers do not understand

GA• Early adopters negotiating

coverage & reimbursement with each payer for each patient by early adopters

Pre-AnalyticalPre-Analytical

Sequence Data InterpretationSequence Data Interpretation

Reporting & Billing Reporting & Billing

Clinical ConsultationClinical Consultation

Sequence Data Generation Sequence Data Generation

Current GA Regulatory Environment is Uncertain

• FDA held meeting to understand early clinical users needs & concerns

• No FDA position/guidance

• No CLIA standards for GA

• CAP Next Generation Sequencing (NGS) Work Group o NGS Checklist

questionso PT Exchange

Pre-AnalyticalPre-Analytical

Sequence Data InterpretationSequence Data Interpretation

Reporting & Billing Reporting & Billing

Clinical ConsultationClinical Consultation

Sequence Data Generation Sequence Data Generation

Pathologists Have an Opportunity to Lead the Medical Community in Genomic Medicine

• No single medical specialty is well informed about Genomic Medicine

• Pathologists have the opportunity to be seen as thought leaders in Genomic Medicine

• While Next Gen technology is rapidly advancing, the growth of the genomics knowledge base will result in a slow evolution of clinical applications

• Pathologists must have a genomics advocacy voice to be seen as leaders in Genomic Medicine

CAP policy and advocacy initiatives preserve our role and assert our leadership in Genomic Medicine…

• 100 new test-specific CPT codes

• CAP at the table on how to regulate LDTs, including genomic tests

• CAP advocating to knock down laws that impede pathologists from releasing pathology results and consulting with patients

• CAP is blocking state laws that encroach on pathologists’ role as a physician

• CAP is a plaintiff in the BRCA lawsuit against Myriad

New Molecular Pathology Codes

New Molecular Pathology Codes

Removing Barriers to Consulting with Patients on

Test Results

Removing Barriers to Consulting with Patients on

Test Results

Preserving Scope of Practice

Preserving Scope of Practice

Resisting Gene PatentsResisting Gene Patents

CAP LDT Oversight Proposal CAP LDT Oversight Proposal