Personalized Medicine: The Changing Landscape of Health Care

The 2nd Biomarker Meeting in Personalized Reproductive

Medicine

Valencia, Spain

11 April, 2014

Edward Abrahams, Ph.D.

President | Personalized Medicine Coalition

Ancient Precedent

“It’s far more important to know what person the disease has than what disease the person has.”

Hippocrates (ca. 400 BCE)

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Moving from Art to Science

“If it were not for the great variability among individuals, medicine might as well be a science, not an art.”

Sir William Osler, Physician (1892)

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The right treatment for the

right person at the right

time

Trial and Error

Personalized Medicine Current Practice

Defining Personalized Medicine

One size fits all

Trial and error

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PCAST Definition of Personalized Medicine

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“Personalized medicine” refers to the tailoring of medical treatment to the individual characteristics of each patient… to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not. President’s Council of Advisors on Science and Technology (PCAST), Priorities for Personalized Medicine, September, 2008

Revised Definition of Personalized Medicine

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Personalized medicine is an evolving field in

which physicians use molecular diagnostic

tests to determine which medical treatments

will work best for the patients. By combining

the data from those tests with an individual’s

medical history and circumstances, health care

providers and patients can develop targeted

treatment and prevention plans.

Reactions to Definitions of Personalized Medicine

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Reactions to PCAST and revised definitions of Personalized Medicine were dramatic. People who saw the new definition responded positively, saying it was clear, easy to understand, and consistent with the term.

Preferred Name for Personalized Medicine

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By far, the two favorite names were “individualized medicine” and “personalized medicine.” The word, “targeted” was also a favorite. “Precision medicine” was more negative than positive; and “stratified medicine” was disliked most of all.

Hope and Fears for Personalized Medicine

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The majority of those surveyed feel excited about personalized medicine. The biggest concerns were regarding cost and access to treatments. The most exciting ideas were around better more informed tailored treatment options

What is Driving Personalized Medicine?

Safer, More Effective Drugs

Faster Time to a Cure

Cost-Effective Healthcare

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The Benefits of Personalized Medicine

•Diagnose disease more accurately

•Select optimal therapies and target medicines and dosages

more precisely

• Increase safety, reduce adverse drug reactions

•Detect onset of disease at the earliest moments

•Shift emphasis in medicine from reaction to prevention

• Increase the efficiency of the health system by improving

quality, accessibility and affordability

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Asthma Drugs 40-70% Beta-2-agonists

Hypertension Drugs 10-30% ACE Inhibitors

Heart Failure Drugs 15-25% Beta Blockers

Anti Depressants 20-50% SSRIs

Cholesterol Drugs 30-70% Statins

Major Drugs Ineffective for Many

Source: Spear B, Heath-Chiozzi M, Huff J Clinical Trends Molecular Medicine 2001; 7(5):201-4. 11

Ineffective Therapies Waste Money

Major Drug

Hypertension Drugs

Ace Inhibitors

Heart Failure Drugs

Beta Blockers

Anti Depressants

SSRIs

Cholesterol Drugs

Statins

Asthma Drugs

Beta-2-agonists

Cost of Ineffectiveness to Healthcare System

$390 million – $1.2 billion

$345 million – $575 million

$2.3 billion – $5.8 billion

$3.8 billion – $8.8 billion

$560 million – $1.0 billion

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Ineffective Therapies Can Cause Harm

Adverse Events

• Estimated 100,000 deaths per year (in 1994; Lazarou et al 1998)

• 6th leading cause of death in the US

• Experienced by approximately 7% of patients (2.2 million) per year

• Medication-related health problems account for an estimated 3% to

7% of hospital admissions (Pirmohamed M, et al 2004)

• During their hospital stay, 15% of patients experienced adverse

drug reactions (Davies, et al 2009)

• Increased patient non-compliance

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The Old Paradigm: Treatment of Disease

Reactive Medical Care

Select Drug

Diagnosis

Switch Drug

Switch Drug Again

Diagnose Disease; Treat Symptoms; Costly, Trial and Error Treatment

Dis

ease S

everity

Time

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Effective, Efficient Health Management

Efficient Medical Care

Health Management; Molecular Screening; Early Detection; Rapid Effective Treatment; Improved Quality of Care

Predisposition

Right Drug

Diagnosis/Prognosis

Screening

Monitoring

Dis

ease S

everity

Time

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Personalized Medicine: Impacts Care

"Disease of the Blood"

Leukemia or Lymphoma

Chronic Leukemia Acute Leukemia Preleukemia

Indolent Lymphoma Aggressive Lymphoma

~38 Leukemia types identified: Acute myeloid leukemia (~12 types) Acute lymphoblastic leukemia (2 types) Acute promyelocytic leukemia (2 types) Acute monocytic leukemia (2 types) Acute erythroid leukemia (2 types) Acute megakaryoblastic leukemia Acute myelomonocytic leukemia (2 types) Chronic myeloid leukemia Chronic myeloproliferative disorders (5 types) Myelodysplastic syndromes (6 types) Mixed myeloproliferative/myelodysplastic syndromes (3 types)

~51 Lymphomas identified: Mature B-cell lymphomas (~14 types) Mature T-cell lymphomas (15 types) Plasma cell neoplasm (3 types) Immature (precursor) lymphomas (2 types) Hodgkin's lymphoma (5 types) Immunodeficiency associated lymphomas (~5 types) Other hematolymphoid neoplasms (~7 types)

60

Years Ago

50

Years Ago

40

Years Ago

Today

5 Year Survival

~0%

70%

Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2002, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2002/, based on November 2004 SEER data submission, posted to the SEER web site 2005.

Source: Mara G. Aspinall, former President, Genzyme Genetics 16

The Blockbuster Model is “Broken”

“The power in tailored therapeutics is for

us to say more clearly to payers,

providers, and patients -- ‘this drug is

not for everyone but it is for you.’”

John C. Lechleiter, Ph.D.

Chief Executive Officer

Eli Lilly and Company

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Trends in R&D Costs and Drug Approvals

0

10

20

30

40

50

60

1975 1980 1985 1990 1995 2000 2005 2010

R&D Expenditures ($ Billions)

New Drug Approvals (3 year moving average)

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October 2, 2013

Decreasing Cost of Genome Sequencing

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Target

Identification

Target

Validation

Lead

Development Preclinical Clinical

Faster path to

disease targets

using genetic data

Speed trials by testing on

patients selected for likely

high response and safety

Safer, More Effective Drugs Identify disease targets, speed clinical trials, and advance more

drugs that are safe and effective for specific populations

Personalized Medicine in R&D

Over 400 drugs currently under review at FDA include biomarkers

100 in late stage oncology clinical trials.

Market

Knowledge of biological

pathways helps eliminate

poor candidates

Target optimal population by

combining drug with

molecular diagnostic test

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Source: Wall Street Journal Copyright 2011 by DOW JONES & COMPANY, INC. Reproduced with permission of DOW JONES & COMPANY, INC.

Tackling Tumors

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As Science Advances, Oncology Drug

Development Accelerates

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9

4

0

5

10

15

20

25

30

35

40

45

BCR-ABL 2001 EGFR 2003 BRAF 2011 ALK 2011

Years From Discovery of Target to Approved

Treatment

Target and Year of Approved Treatment

Adapted from Gerber and Minna Cancer Cell: 18: 548, 2010 23

Many Biopharma Companies have Launched

Therapeutics Informed by CDx Tests

Source: L.E.K.

Launch timeline of targeted therapeutics with required or recommended CDx

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Marketed Therapeutics with an Associated

CDx Test Generate $12B

Source: L.E.K.

Note: * Branded drug sales; does not include sales of Zelboraf (~35M in 2011) and Xalkori (sales unkown), both approved Aug 2011

** Other includes: Iressa (AstraZeneca), Camptosar (Pfizer), Selzentry (Pfizer), Tegretol (various), Ziagen (GSK), Imuran (GSK)

*** Other includes infectious disease and CNS 25

Note: * Includes non-unique tests

Source: L.E.K.

Significant Growth for Commercial

Personalized Medicine Diagnostics

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Personalized Medicine:

How Will It Affect Healthcare?

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Changing Role of the Patient

• Greater knowledge of one’s genetic risks

• Actionable lifestyle prescription for reducing risk of disease

• Greater control and patient-centered access to medical records

• Treatment decisions will be improved by patient education

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Changing Role of the Health Care Provider

• Health care providers as manager, rather than repository of medical knowledge

• Greater reliance on HIT for decision support

• Improved care through use of aggregate patient data

• Highly networked, team-based care

• New ethical and legal issues/quandaries

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New Business Strategies for Pharma

• Uncertain economics of drug development and commercialization

• Regulatory mandates could disrupt development budgets and market plans

• “Personalization” of drugs will require partnering with diagnostics companies

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New Demands On and From Payers

• Greater emphasis on clinical validity and utility of diagnostic tests

• Increased need to demonstrate cost efficiencies

• Proactive strategies to limit reimbursement

• Increased pressure to change paradigm towards preventive medicine

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Personalized Medicine Will Become

Fundamental to Our Healthcare Systems

• Our current healthcare practices cannot continue and still be affordable.

• Pharmaceutical companies need to increase their probability of technical success to maintain profitability.

• The public is genuinely interested in genetic information and in having personal choices.

• We have a regulatory framework that is being designed to meet our future needs.

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Making the Case for Personalized Medicine

“We face significant challenges in

accelerating growth in this field –

scientific, business, regulatory and policy

challenges. Together we must break

down the barriers and move personalized

medicine forward.”

John Castellani

President and Chief Executive Officer

Pharmaceutical Research and Manufacturers of America (PhRMA)

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Policy Issues In Personalized Medicine

Personalized Medicine

Reimbursement

Health care Provider

Education and Adoption

Comparative Effectiveness

Research

R&D Incentives

Intellectual Property

Privacy / Ethics

Patient Education

Regulation

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Barriers Implementing Personalized Medicine

”There is nothing more difficult . . . than to take the lead in the

introduction of a new order of things. For the reformer has

enemies in all those who profit by the old order, and only

lukewarm defenders in all those who would profit by the new

order. This indifference arises partly from fear of their

adversaries . . . and partly from the incredulity of mankind, who

do not truly believe in anything new until they have had actual

experience of it.”

— Niccolo Machiavelli

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The Personalized Medicine Coalition,

representing innovators, scientists, patients,

providers and payers, promotes the

understanding and adoption of personalized

medicine concepts, services and products to

benefit patients and the health system.

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1710 Rhode Island Ave., NW

Suite 700

Washington, DC 20036

202.589.1770

www.personalizedmedicinecoalition.org