Personalized Medicine On Deck HomeRuns and StrikeOuts Ahead. Mara G. Aspinall Molecular Summit February 2009

Transcription

1 Personalized Medicine On Deck HomeRuns and StrikeOuts Ahead Mara G. Aspinall Molecular Summit February 2009

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5 22 hours and 44 minutes until Pitchers and Catchers report! Personalized Medicine on Deck Home Run or Strike Out Ahead? Mara G. Aspinall Molecular Summit Philadelphia, Pennsylvania February 2009

6 Personalized Medicine What is it? Why now? When will it be real? Call to Action Personalized Medicine Old Paradigm: Trial and Error Medicine Successful When it Leads to Innovation and Improves Standard of Care. Fails When We Settle for Trial and Error Medicine AS the Standard of Care.

7 Personalized Medicine New Paradigm: Personalized Medicine Linking Tests to Action and Therapy Observation Test Action Predictable Response Breaking The Cycle of Trial and Error Medicine Patients Don t Have Time for Trial & Error Disease 1 Year Survival Lung cancer 42% Colorectal cancer 76% Chronic myeloid leukemia (CML) 93% 63% Heart failure 74% End stage renal disease 78% 2007 USRDS Annual Data Report Levy, et. al., Long-term trends in the incidence and survival from heart failure, NEJM, 2002; 347(18): CancerMpact, MattsonJack; NCI SEER data, average across all stages at Dx

8 Personalized Medicine Why is it Important? Diagnosis Save Lives Diagnosis Save Money Personalized HEALTH CARE Why is it Important? Diagnosis Save Lives Diagnosis Save Money Monitoring Ensures Both

9 Patient LifeCycle Management Predisposition Initial Diagnosis Family Genetics & Co-morbidity Phenotype & Genotype Pathology Molecular Diagnosis Imaging Recurrenc e Monitoring Therapy Choice Tx Effectivenes s Assessment Therapy Safety Managem ent Personalized Medicine Test Categories Drug Selection Breast Cancer Herceptin HER2 Drug Dosage Colorectal Cancer Camptosar UGT1A1 Drug Efficacy Chronic Myelogenous Leukemia Gleevec Quant BCR-ABL Disease Status Chronic Lymphocytic Leukemia Campath Minimal Residual Disease Recurrence Risk Breast Cancer Oncotype DX Multivariate Analysis Predisposition Breast Cancer BRACAnalysis Gene sequencing, risk analysis

10 Personalized Medicine Saves Lives 100 Years Ago 80 Years Ago 60 Years Ago Disease of the Blood Leukemia or Lymphoma Chronic Leukemia Acute Leukemia Preleukemia Indolent Lymphoma Aggressive Lymphoma 5 Year Surviva ~ 0% Today 38 Leukemia types identified: 51 Lymphomas identified: Acute myeloid leukemia ( 12 types) Mature B-cell lymphomas ( 14 types) Acute lymphoblastic leukemia (2 types) Mature T-cell lymphomas (15 types) Acute promyelocytic leukemia (2 types) Plasma cell neoplasm (3 types) Acute monocytic leukemia (2 types) Immature (precursor) lymphomas (2 types) Acute erythroid leukemia (2 types) Hodgkin s lymphoma (5 types) Acute megakaryoblastic leukemia Immunodeficiency associated lymphomas ( 5 types) Acute myelomonocytic leukemia (2 types) Other hematolymphoid neoplasms ( 7 types) Chronic myeloid leukemia Chronic myeloproliferative disorders (5 types) Myelodysplastic syndromes (6 types) Mixed myeloproliferative/myelodysplastic syndromes (3 types) 70 % Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, , National Cancer Institute. Bethesda, MD, based on Nov 2004 SEER data submission, posted to the SEER web site Molecular Characterization Standard Practice In Hematologic Oncology Morphology Evaluation + Fluorescence-Activated Cell Sorting + Cytogenetic Analysis + Molecular Analysis Expanded Characterization and Response Prediction Identification of t(15;17) translocation in AML patients leads to specific treatment (ATRA) which changed the overall survival from 0% 40 years ago to 80% now

11 Personalized Medicine Reduces Ineffective Treatment in Colon Cancer kras Testing Treat with Erbitux Do Not Treat Treat with Erbitux Treatment Success Langreth, R. (2008), Imclone s Gene Test Battle, Forbes.com, 16May Personalized Medicine is Cost Effective in Treatment of Colon Cancer $200,000 $150,000 $100,000 $50,000 $0 Erbitux Treatment Cost Comparisons with and without kras Testing to Direct Personalized Treatment $22,800 $38,000 Average Treatment Cost (per person) With kras Testing $97,022 $156,554 Average Treatment Cost (per success) Without kras Testing 60% reduction in cost per success 40% of patients spared side effects from ineffective treatment Overall success rate is unchanged at 25% Langreth, R. (2008), Imclone s Gene Test Battle, Forbes.com, 16May

12 Personalized Medicine is Beneficial in Treatment of Pancreatic Cancer Suspected Pancreatic Cancer Watch And Wait Pancreatectomy Increased Risk Insulin Insufficiency Two Bad Choices Suspected Pancreatic Cancer PathFinderTG Diagnostic 30% 70% Pancreatic Cancer Treat Aggressively Benign Condition Do Nothing Informed Choices Rina Wolf Testimony before House Committee on Small Business, Subcommittee on Regulations, Healthcare and Trade, May 14, 2008 Personalized Medicine What is it? Why now? When will it be real? Call to Action

13 Why Now? The Human Genome Project Why Now? Explosion of Imaging and Omics Proteomics Allergenomics Bibliomics Biomics Cardiogenomics Cellomics Chemogenomics Chemoproteomics Chromatinomics Chromonomics Chromosomics Combinatorial Peptidomics Computational RNomics Cryobionomics Crystallomics Cytochromics Cytomics Degradomics Ecotoxicogenomics Eicosanomics Embryogenomics Enviromics Epigenomics Epitomics Expressomics Fluxomics Fragmentomics Fragonomics

14 Why Now? Diagnostic Technology Has Improved Past Macro Level Testing Tests differentiated disease from non-disease Disease defined by location and size Today Molecular Level Testing Disease defined by individual biology and /or DNA of tumor or virus Tests to subcategorize disease: Why Now? Diagnostic Technology Has Improved Tomorrow Predictive Testing Multiple technology platforms Multi-factorial testing Multi-gene signatures Multiple Sample Types Urine, Saliva, Breath, others? Increased Use of Diagnostic Imaging & Availability of these Tests by Consumers

15 Why Now? Increased Government Interest FDA In-vitro Diagnostic Multivariate Index Assay (IVD MIA) Draft Guidance Pharmacogenomics voluntary data submission HHS Secretary s Committee on Genetics, Health and Society (SACGHS) Report recommends filling gaps in test oversight President s Council on Science and Technology Report of Personalized Medicine Why Now? FDA Intervention Potential FDA Stance On Valid Genomic Biomarkers on Approved Drug Labels Drugs with Labels Containing Pharmacogenomic Information 121 Drugs with Tests Required - 2 Drugs with Tests Recommended - 3 Drugs with Tests for Information Only 16 Drugs with No Test Mentioned 100 Clinical Ligand Assay Society 32 nd International Meeting Louisville, KY May 22, 2006 Felix W. Frueh, PhD Associate Director for Genomics, Office of Clinical Pharmacology CDER/FDA

16 Personalized Medicine What is it? Why now? When will it be real? Call to Action The Personalized Medicine Timeline Fear Value Acceptance

17 The Personalized Medicine Timeline Fear Payers: Adds to My Cost Without Return Treating Physicians: Too Prescriptive for Me Patients: Will I Be Denied Access to New Drugs? Regulators: How Do We Handle New Complexities? Diagnostics: More Tests With Poor Reimbursement Pharma: Reduces My Market Pathologists and Radiologists: Reduces My Market Fear Spending Up but New Drug Approvals Not New Drug Approvals PhRMA R&D Spending Pharmaceutical Research and Manufactures of America: Pharmaceutical Industry Profile

18 Fear Blockbusters Going Off Patent 105 blockbusters with $237 billion in sales 37 % of all prescription drug sales 7 of top 10 drug launches in 2006 were generics $ Billion $13 $21 $15 $9 $12 $21 $ Big Pharma Faces Grim Prognosis, Wall Street Journal, 12/06/2007 Cowen and Company Fear (and Opportunity) Drug Efficacy is Too Low Therapeutic Area Effective Rate (%) Oncology Alzhe ime r's Incontinence Hepatitis C virus Osteoporosis 25% 30% 40% 47% 48% Rheumatoid arthritis Migrane Cardiac Arrythmias Asthma 50% 51% 60% 60% Spears et al. TRENDS in Molecular Medicine Vol. 7 No. 5 May 2001

19 Fear (and Opportunity) Adverse Events are Too High 2.2 Million People Impacted Annually $177 billion annual cost Single largest cause of drug market withdrawals Cause Of Death Number Of Deaths Heart Disease 652,091 Malignant Neoplasms 559,312 Cerebrovascular Disease 143,579 Lower Respitory Disease 130,933 Accidents 117,809 Adverse Drug Reactions 106,000 National Vital Statistics Reports, Vol. 56, No. 10, March 7, 2008, 2001United States Data Fear (and Opportunity) Prescription Compliance is Too Low Stops before completed 29% Takes Medication as Prescribed 25% Fills but Does not Take 12% Does not Fill 12% Takes less than Prescribed 22% Source: American Heart Association

20 Fear (and Opportunity) Drug Reimbursement System Changing? Reimbursement ONLY if patient benefits from drug REFUND if patient does not benefit after treatment Current Examples: Velcade for multiple myeloma Johnson & Johnson and Government Payors in UK and France Full refund to payor if patient does not achieve 50% biomarker reduction Oncotype DX Genomic Health and United Healthcare Price adjusted if tests do not show change in clinical practice Pricing Pills by the Results, New York Times, July 14, 2007 Velcade For Multiple Myeloma Protocol Patient is treated with a maximum of 4 cycles of treatment ($24,800 US) Serum M protein, a biomarker for tumor load, is monitored with blood or urine test Electrophoresis: Normal plasma Serum M protein Nature Reviews, Drug Discover: December 2007, v 6, p 945

21 Velcade For Multiple Myeloma Biomarker is linked to drug efficacy Biomarker results are then linked to payment Complete response (CR): minimal / no serum M protein - PAID Partial response (PR): > 50 % reduction of serum M protein PAID Minor or Minimal response (MR): < 50 % reduction of serum M protein - REFUND Nature Reviews, Drug Discover: December 2007, v 6, p Pathologist & Radiologist Fear? New Sample Types Beyond Tissue Molecular Blood Tests Circulating Tumor Cells Breath Tests Urine Tests

22 Pathologist and Radiologist Fear? Molecular Tests are Exploding IVD-MIA Devices Number Today In-Development Source: In Development Coalition for 21 st Century Medicine Survey 2007 Venture Capital is focused on Diagnostics Increased Venture Capital Spending $500 $400 $300 $200 $100 $- $ (Millions) $120 $170 $160 $184 $297 $409 $ Year Nature Biotechnology Volume 24 Number 8 August 2006, BioCentury's BCIQ, Genzyme Analysis

23 Personalized Medicine What is it? Why now? When will it be real? Call to Action Call to Action Need to Embrace the Future Present Future Morphology Plus Imaging Molecular Tests Stable Base of Technology Many New Emerging Technologies Convergence of Technologies Single Gene Tests Multi Gene / Multi Technology Tests Tissue Samples Multiple Sample Types Diagnosis Intepretation & Timeframe Controlled by Pathologist or Radiologist Molecular Tests & Point of Care Diagnostics enable Treating Physician to directly diagnose

24 Call to Action Pathologist and Radiologists Need to : - Own Personalized Medicine - Source of expertise on all tests available - Interpreter and consolidator of all test results - Educator of all other physicians on diagnosis Move Industry from Fear to Acceptance Moving From Fear To Acceptance Physician Education Data Integration & Ownership of EMR Policy Reimbursement & Regulatory Aspinall and Hamermesh, Harvard Business Review, Oct 2007

25 Move From Fear to Acceptance Physician Education Build commitment through education of community physicians Publish new practice guidelines tests and technologies Integration and Ownership of EMR Create Data on the positive outcomes and economics of appropriate use of PM diagnostics Leadership in building the EMR Policies Needed Reimburse on value not activity Regulatotion to encourage diagnostic & drug combinations Embrace Era of Diagnostics For Improved Outcomes Hospitals Today Organ-Based Treatment Paradigm Brain Cancer Leuke mia Pancreat ic Cancer Lung Cancer Colon Cancer Breast Cancer

26 Hospitals in the Future Mechanism-Based Treatment Paradigm jak-2 c-kit P53 EGFR kras Her-2 Future Health Care Spending Health Care $ Individual Health Care Spending Curve Current Practice Improved Quality of Life & Financial Savings Investment In Diagnostics And Prevention Potential o Personaliz Medicine Years Source: Deloitte Development LLC 2006

27 Acknowledgements David Turnquist, Boston College Deloitte Center for Health Solutions Personalized Medicine Coalition The Personalized Medicine Timeline Value (Opportunity) Treating Physicians: More Precise Care Payers: Reduce Spend on non-effective therapies and adverse events Patients: More effective treatments with fewer side effects Regulators: Guidelines for diagnostic/ therapeutic use Diagnostics: Value Based Reimbursement Pharma: Targeted Pipeline & Products benefit 80% of Patients

28 Pathologist Fear? New Technology Trumps Morphology Currently, 17 % of Burkitt Lymphoma are incorrectly diagnosed as Diffuse Large B Cell Lymphoma Classic Burkitt Lymphoma Atypical Burkitt Lymphoma Diffuse Large B Cell Lymphoma Source: Louis Staudt, MD, PhD. National Cancer Institute Pathologist and Radiologist Fear? New Technology Beyond Morphology Gene Expression Burkitt Differentiates Diffuse Burkitt Large Lymphoma from Diffuse Lymphoma B-cell Lymphoma Large B Cell Lymphoma, Improving Patient Care Classic Atypical Louis Staudt, MD, PhD, National Cancer Institute