An Innovation Revolution — How Genetic Testing is Improving Health and the Economy

1. An Innovation Revolution — How Genetic Testing is Improving Health and the Economy Kenneth Sisco, MD, PhD, FCAP Medical Director Quest Diagnostics March 17, 2011

2. Medicine of the past: “Trial-and-Error” medicine Observe Diagnose Treat Monitor response Adjust

3. Trial-and-error medicine often works, but… Treatment Treatment Treatment Disease Treatment Treatment Treatment Treatment Treatment

4. Trial-and-error medicine is often imprecise One-year survival rate for certain cancers Disease Delays in care Costs Inappropriate or unnecessary utilization Side-effects 100,000 new cases early-stage breast cancer (estrogen-Receptor positive; node negative) • Every year in U.S., adverse drug reactions = • 100,000 deaths • 2,000,000 ADRs Standard practice in 90% = chemo (after surgery/radiation) 70% receive no benefit from chemo Source: M Aspinall presentation, 2008;Harvard Business Review 2007; Mayo Clinic; NIH

5. Personalized medicine: precise diagnosis and treatment Observe Diagnose Precisely Treat Precisely Manage Trial and Error Medicine Treatment Disease Personalized Medicine

6. With new knowledge about the disease, we can…

7. Diagnose disease more precisely Genetic tests identify DNA of childhood leukemia, enabling physicians to choose the treatment that fits it precisely. • Acute lymphoblastic leukemia is most common form of childhood leukemia • Genetic tests identify subtypes; allow precise treatment and timing • Today’s cure-rate exceeds 80% vs. 4% in the 1960s The impact of genetic tests and genome-based cancer drugs on survival of childhood leukemia 80% 4% Source: New England Journal of Medicine, 2006, 200l; Personalized Medicine Coalition, 2006.

8. Select treatment based on genetic fingerprint Genetic tests identify the genetic makeup and rapid mutation of an individual’s HIV virus and pinpoint the most effective drug. • Genetic tests + HIV drugs = a “one-two” punch… • Dramatic decline in deaths • Patients live normal lives • From “Killer” to “Chronic” • The reason: Genetic tests tell docs which drug combo will work best • Tests also let docs adjust drugs to combat fast-morphing virus The effect of lab tests combined with anti-HIV drugs Source: Journal of American Medical Association, 2006; New England Journal of Medicine, 1998; Centers for Disease Control and Prevention

9. Predict risk before symptoms appear Genetic test identifies variations in the BRCA 1 and BRCA 2 genes that increase risks for breast and ovarian cancer. • Genetic tests identifies increased hereditary risk for breast and ovarian cancer • Lifetime risks: 35-85% of BRCA women will develop breast cancer vs 13.2 percent for others • Knowledge of increased risk allows preventive measures • closer monitoring, • risk avoidance, • preventive surgery or chemotherapy Lifetime risk of developing breast cancer… …with BRCA 1 and 2 = 36% - 85% …without = 13% Lifetime risk of developing ovarian cancer… …with BRCA 1 and 2 = 16% - 60% …without = 1.7% Source: National Cancer Institute

10. Genetic tests can begin to transform health costs Rx = $300 Billion Annually • US spends $300 Billion on pharmaceuticals each year • Genetic tests can help physicians better target • Right patient, right drug • As a result, potential savings through better targeting via genetic testing Non therapeutic responders = $60B - $225 Billion annually 75% Potential savings via better targeting: Up to $110 Billion 20% Source: M Aspinall, Harvard Business Review, 10/2007; Spear,Trends in Molecular Medicine, 5/2001; IMS, 2010

11. Genetic testing helps get right drug, to right patient Percentage of patients for which standard drug treatment provides effective therapy is shown in blue. Source: Aspinall, Harvard Business Review, October, 2007; Spear,Trends in Molecular Medicine, May 2001

12. Greater economy through more precise dosing Genetic tests for dosing of warfarin cut hospitalization • Warfarin = most common drug thinner • Very difficult to dose • Too much = bleeding • Too little = strokes • Genetic testing to guide physicians in dosing: • Now on FDA label • JACC study (6/10) shows 31% drop in hospitalization • 2006 Brookings/AEI estimate: $1.1 billion savings annually Genetic test leads to drop in hospitalization Overall Clots/Bleeding Source: Journal of the American College of Cardiology, June, 2010; Brookings/AEI, 2006

13. Breast cancer: getting right drugs to right patients Cost of Herceptin per Patient • 200,000 new breast cancer cases annually • 30% have overabundance of HER2 protein • So regular chemo doesn’t help; Herceptin does • Genetic testing tells doctors which patients have HER2 • Reduces risk of death by 33% and risk of recurrence by 52% • $24K savings per patient Savings: $24K per patient $79,181 $54,738 Without HER2 Test With HER2 Test Source: M. Aspinall, Presentation, 3/28/08; J Clin Oncol (2004) ; NEJM (2005)

14. Metastatic colon cancer: right drugs, right patients Cost of drug per patient: $71,120 • 40% of patients with metastatic colon cancer do NOT benefit from standard therapy • KRAS gene mutation • Genetic test identifies those patients • Testing = select right drug; avoid ineffective treatment; reduce adverse events = $ savings • One estimate: $700 million savings annually if test is done before prescribing drug. Cost of test per patient: $452 Source: Shankaran, V, et al, ”Economic Implications of KRAS testing in metastatic colorectal cancer,” Paper presentation, ASCO, 2009; Manci, Am J Health-Syst Pharm., 2009

15. What does the future hold? • Molecular approaches in screening and monitoring an increasing number of cancer types • Molecular approaches in treating inherited gene mutations, as well as acquired diseases • Evolution of point-of-care testing, as well as microarray analysis of disease susceptibility