Innovating to Better Care:

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23 Οκτ 2013 (πριν από 3 χρόνια και 7 μήνες)

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Lydia Pan, PhD

Director, Worldwide Policy, Pfizer Inc.


Presentation to the Cancer Action Coalition of Virginia

September 12, 2013

Innovating to Better Care:

How personalized medicine is changing the
biopharmaceutical marketplace


Personalized Medicine: Towards a Definition

“Personalized medicine” refers to the tailoring of medical treatment to the
individual characteristics of each patient. It does not literally mean the creation of
drugs or medical devices that are unique to a patient, but rather the ability 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
.


Report of the President’s Council of Advisors on Science and Technology,

September 2008


The right
drug


…for
the right person




…in
the right
dose







…at the right time


1

Older Drugs were Developed Empirically


Source of data: Brian B. Spear, Margo Heath
-
Chiozzi
, Jeffery Huff, “Clinical
Trends in Molecular Medicine,” Volume 7, Issue 5, 1 May 2001, Pages 201
-
204.

2

Today’s Medicines are Developed with
More Precision



Medicines targeting
patient segments that
will have an
optimal
response

to therapy

Building disease
understanding to
identify the right
pathways and targets

Linking disease
understanding
and clinical
outcomes

Precision Medicine

Segmented (not personalized)

3

Recognition of Leukemia and Lymphoma
Sub
-
types has Improved Outcomes

100

years ago

Disease of the blood

80

years ago

Leukemia or lymphoma

60

years ago

Chronic leukemia

Acute leukemia

Preleukemia

Indolent lymphoma

Aggressive lymphoma

Today

~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 myelomoncytic 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 neoplasm's

(~7 types)

5
-
Yr

Survival

~0
%

70%

Source:
Malorye
, Allison. “Is Personalized Medicine Finally Arriving?”
Nature Biotechnology
,
May 2008

4

The Human Genome: A Great Opportunity
for Drug Discovery?

Biopharmaceutical R&D Investment and
New Medicines Approved

Sources:
Paraxel's

Pharmaceutical R&D Statistical Sourcebook 2005/2006; FDA;
PhRMA


6

12

22

30

20

21

20

23

23

30

26

25

22

28

53

39

30

25

27

24

17

21

36

20

22

18

24

26

21

30

39

3.2

3.6

4.1

4.8

5.7

6.5

7.3

8.4

9.6

11.6

12.7

13.4

15.2

16.9

19.0

21.1

22.7

26.0

29.8

31.0

34.5

37.0

39.9

43.4

47.9

47.4

46.4

50.7

48.6

48.5

$ Billiions

Number of Products

Year

Genomic
-
based Research Enables
Precision Medicine

Right Target

Right Patient

Goal to

improve survival

7

Drug targeted to specific
oncogene or aberrant
pathway driving the
specific tumor

Patient identified through
molecular profiling of
their tumor

Ultimate objective is to
improve survival

New treatment

Comparator

0

6

12

18

24

30

36

0

0.2

0.4

0.6

0.8

1.0

Overall Survival Probability

Months of survival

Phase 1

Phase 2

Phase 3

Clinical Development

Challenges for Coordination of

Rx/
Dx

Co
-
development

PMA (CDRH)

CDER/CBER

The FDA prefers to review both Rx &
Dx

applications concurrently.

Sponsor must coordinate between different FDA Centers

FDA has multiple programs to expedite drug/biologic development and review:


Fast Track, Accelerated Approval, Breakthrough Therapy, Priority Review

CDRH does not have similar mechanisms to accelerate diagnostic approval.

Diagnostic

Therapeutic

Drugs Labels with Genomic Biomarker
Information

Testing required


Trastazumab

/ breast cancer


FISH/IHC HER2




Panitumumab

/ colon cancer


KRAS
wildtype


V
emurafenib

/ melanoma


BRAF V600E


Crizotinib

/ NSCLC



ALK gene rearrangements

Ivacaftor

/ cystic fibrosis


CFTR G551D

T
esting

recommended


Abacavir

/ HIV AIDS



HLA
-
B 5701 variant


Irinotecan

/ colon cancer


UGT1A1 variant


Azathioprine

/ autoimmune


Thiopurine

methyltransferase


Warfarin

/ thrombosis, CV prophylaxis

CYP2C9, VKORC

Informational tests


Fluoxetine

/ depression


CYP2D6


Codeine / analgesia



CYP2D6





Clopidogrel

/ CV prophylaxis


CYP2C19


Chloroquine

/ malaria



G6PD deficiency



Adapted
from
Nature Biotechnology
, 25, 509
-
517,
2007; Table of
Pharmacogenomic

Biomarkers in Drug Labels
http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm


9

FDA

Framework for
Personalized Medicine
:

A

Mosaic


of Guidance Documents

Document Type

Title

Date

Concept Paper

Drug
-
Diagnostic Co
-
Development

April 2005

Guidance

Pharmacogenetic

Tests and Genetic Tests for
Heritable Markers

Feb 2006 (draft)

June 2007 (final)

Draft Guidance

Pharmacogenomic

Data Submissions

Aug 2007

Draft Guidance

In Vitro Diagnostic Multivariate Index Assays

Sept 2006 (draft)

Feb 2007 (public meeting)

July 2007 (revised)

2010 (withdrawn)

Draft Guidance
(FAQ)

Commercially Distributed In Vitro Diagnostic
Products Labeled for Research Use Only or
Investigational Use Only

June 2011

Draft Guidance

In Vitro Companion Diagnostic Devices

July 2011

Guidance

Clinical
Pharmacogenomics
: Premarketing
Evaluation in Early Phase Clinical Studies

January 2013

(draft Feb 2011)

Additional guidance documents forthcoming

I

III

II

III

II

CMS

(CLIA)

FDA

510k

PMA

All
Lab
-
Developed Tests

Distinct pathways
for
LDTs and
Dx

test
kits

Certification of laboratory
performance standards

Multiple Ways for Tests to Reach the
Marketplace

Risk
class

Clinical utility
required

Regulator

FDA wants all
CDx

to go
through PMA

Personalized Medicine: Key Components



Science & Technology


Driving the understanding of disease and the discovery and

development of medicines


Regulatory science advances




Medical Practice

-
What’s best for the patient?

-
Changes in medical practice



Health Care Environment

o
How do we get personalized

o
medicines to patients?



1
2

Understanding of Oncologic Drivers
is
Rapidly Increasing

References: 1.
Massachusetts
General Hospital, data on file

2.
Horn L, Pao W.
J Clin Oncol
2009;26:4232

5

13

Adenocarcinoma 1999

Histology
-
driven Selection

K
-
RAS

EGFR

B
-
RAF

HER
-
2

PIK3CA

ALK

MET


Unknown

Adenocarcinoma 2011

Targeting Oncogenic
Drivers
1


Evolving Personalized
Paradigm

Metastatic disease (
stage
IIIB/ IV)

Biomarkers can direct treatment
towards targeted therapy or
clinical trials (where
available)

EGFR

K
-
RAS

ERCC1

ALK

TS

B
-
RAF

HER
-
2

Traditional
Paradigm

Non
-
squamous
cell carcinoma

Metastatic disease (stage
IIIB/
IV)

Squamous
cell
carcinoma

Creating a New Paradigm for NSCLC
Treatment


Oncologist
sole treatment
decision maker


Treatment
decisions depend on histology


More
complex decisions involving more stakeholders
beyond oncologist (surgeon, pathologist)


Education required to integrate molecular diagnostics
into treatment decisions


Need for multiple molecular
Dx

creates competition for
available tissue, budget, manpower


Not a “simple” issue of a single drug
-
diagnostic
combination

Multiple test options

Biomarkers Support Expansion of Use

Therapeutic

Biomarker

Indication(s)

GLEEVEC
®

Imatinib

C
-
Kit

Gastrointestinal
stromal

tumors,
aggressive systemic
mastocytosis


Philadelphia
Chromosome

chronic myeloid leukemia, acute
lymphocytic leukemia

PDGFR

myelodysplastic/ myeloproliferative
diseases

FIP1L1
-
PDGFRα

hypereosinophilic

syndrome and/or
chronic
eosinophilic

leukemia

Adapted from GLEEVEC® prescribing information (www.novartis.com)

15

Payers Must Determine How to Pay for
Personalized Medicine

Test Coding:


AMA created

new Molecular Diagnostic

CPT codes for 2013


Retirement of code
-
stacking


Unique tests still not identified (McKesson Z
-
codes)

Coverage and Reimbursement:


CMS rolling
out new policies for molecular diagnostics


MolDx

test payments being set at local level by gap
-
filling; process
has not been transparent


Proposed payment determinations for products paid under the CLFS
included the decision NOT to pay for algorithm portion of multi
-
analyte

tests


Increasingly, payers are demanding high levels of clinical evidence to
justify the reimbursement of personalized medicine products


Challenges to generating timely evidence without denying or delaying
access to treatment


Targeted therapeutics increasingly subject to utilization management tools



16

Challenges to Personalized Medicine in
the Marketplace


Precision medicine may drive efficiencies in drug
development but application of technologies isn’t cheap


Drug development may or may not be less costly


If targeting smaller,

more

defined populations, medicines
should have greater efficacy / safety risk ratios but also
likely be more expensive


Diagnostics landscape is rapidly evolving


needs
investment to sustain innovation


Integrating each new intervention into healthcare
management takes time


Growing pressure to show PM improves health outcomes


Value loss if access is restricted

17

Rx to Deliver the Pipeline for Personalized
Medicine


Aggressive application of science to R&D


Informatics tools to analyze

large, multi
-
dimensional data
sets


Closer
industry
-
academia collaboration
to drive customized therapy
solutions


Novel clinical trial designs
that incorporate new drug development tools


Opportunities to
add value to existing and potential medicines


Secure systems
that allow
safe sharing of data
between health care providers,
industry and regulators to streamline development and approval processes


Collaborative

relationships with regulators
that strengthen patient safety but
also speed the approval of novel biomarker applications

and
Dx

technologies


Evidence standards
to demonstrate the effectiveness of diagnostics in
improving patient outcomes


18

Toward a Health Care System that Delivers
the Value of Personalized Medicine


Data systems
that assure security and access to the growing body of
patient data


Quality standards
to insure data compatibility and comparability


Integrated health information
: a complete systems
-
based readout
of the health status of an individual in a given environment


Physicians

need easy
-
to
-
interpret results


user
-
friendly technological interface


data from multiple sources


continuously refined algorithms and

database updates


Enabling functions
: standards,

infrastructure, systems approach,

sharing mechanisms


Education

along the entire health care ecosystem


Policy will determine success or failure of

personalized medicine implementation

19

Thank You!


Questions

???

20