conference logo slide...european halo effect peripheral arterial disease (pad or pvd) 26% metabolic...

The Problem

◼ Cardiovascular prevention trials are large, long and expensive

• 10,000+ patients

• Years of patient follow-up

• € 100,000,000+ development cost

◼ Many patient groups-data from one group may not be relevant to others

How can MR help design the clinical program to maximize revenue and minimize development time and cost?

Opportunity for MR

◼ MR traditionally develops target product profile

◼ High cost of CV clinical development leads to a new MR opportunity

• ID patient populations• Trade off revenue and cost

The Approach

How do cardiologists think about CV risk?

30 Key Opinion Leader Interviews

How will MDs extrapolate data?

Web survey: 200 cardiologists & PCPs

How to trade off revenue and costs?

Patient Rx versus clinical cost and time

Objectives

◼ Quantify the revenue impact of:• Registration studies (baseline)

• Four different patient populations

◼ Incremental impact of:• Biomarker studies

• Surrogate endpoint studies

15 scenarios in all

Peripheral

Arterial Disease

(PAD or PVD)

Cerebrovascular

Disease

(CEVD)

Coronary

Artery

Disease

(CAD)

CV Risk Stratification

BMI > 30

Abdominal Fat

> 140 systolic

or

> 90 diastolic

LDL > 160 mg/dL

HDL < 40 mg/dL

Obesity Dyslipidemia Hypertension SmokingType II

DiabetesAge

Age:

M > 65, 55, 45

F >75, 65, 55

PTCA

CABG

ACS

Post MI

Unstable

Angina

Single

Risk

Factors

Stroke

Carotid

Disease

Documented

Carotid

Narrowing

Intermittent

ClaudicationPrevious

Event

Multiple Risk Factors including

“Metabolic Syndrome”

Inc

rea

sin

g R

isk

of

CV

Eve

nt

or

De

ath

Type II

Diabetes

Coronary

Artery Disease

(CAD)

Cerebrovascular

Disease

(CEVD)

Peripheral

Arterial Disease

(PAD or PVD)

CV Risk Stratification - Qualitative Risk

Model Schematic

or or

CAD or CEVD or PVD w/ DM

Secondary

PreventionPost-Primary

Event

Primary

PreventionPre-Primary

Event

Inc

rea

sin

g R

isk

of

CV

Eve

nt

or

De

ath

BMI > 30

Abdominal Fat

> 140 systolic

or

> 90 diastolic

LDL > 160 mg/dL

HDL < 40 mg/dL

Obesity Dyslipidemia Hypertension SmokingType II

DiabetesAge

Age:

M > 65, 55, 45

F >75, 65, 55

PTCA

CABG

ACS

Post MI

Unstable

Angina

Metabolic

Syndrome

Risk

Factors

Stroke

Carotid

Disease

Documented

Carotid

Narrowing

Intermittent

Claudication

Hypertension

Plus One Other

Risk Factoror

or

Eligible US patients slightly outnumber

those in Europe

Patients Eligible for Treatment (MM)

1.0

2.0

3.0

4.0

5.0

6.0

CV+DM DM CAD CEVD PVD HBP+1 Met. Syn. HBP

Millio

ns o

f P

ati

en

ts

U.S.

Europe

◼ A leading pharmaceutical company will offer an alternative

add-on therapy for CV patients who have documented CV

disease or are at risk for CV disease and currently receiving

standard clinical therapy.

◼ The product has the following characteristics:

• Novel mechanism

• Oral, once daily in tablet form

• Reduces events/revascularization procedures by 25%

• No increase in adverse drug events

• No additional side effects or monitoring

• No clinically significant drug-drug interactions with

commonly co-prescribed medications

• Price comparable to Lipitor

Product Profile

Physician Comments on Product Profile

◼ First in class-cardiologists had little basisfor comparison with alternatives

◼ Interviewees expect mortality data inaddition to “events”

◼ Cardiologists need good safety data

Type II Diabetes32%

CerebrovascularDisease (CEVD)

58%

Coronary Artery Disease (CAD)

42%

US Halo Effect

Peripheral Arterial Disease (PAD or PVD)

35%

Metabolic Syndrome27%

Hypertension plus one risk factor

30%

Hypertension26%

CAD or CEVD or PVDw/ Type II Diabetes

45%

Regulatory approval

6.7 MM total patients

45%

32%

45%

28%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

CV + DM DM CADCEVD/PAD

PrimaryPrevention

Pe

rce

nt

of

Pa

tie

nts

0.7

1.0

2.42.6

0.5

1.0

1.5

2.0

2.5

CV + DM DM

Pa

tie

nts

(M

M)

CADCEVD/PAD

PrimaryPrevention

Type II Diabetes25%


55%


32%

European Halo Effect


26%

Metabolic Syndrome23%


25%

Hypertension22%


42%

5.5 MM total patients

42%

25%

38%

23%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

CV + DM DM CADCEVD/PAD

PrimaryPrevention

Pe

rce

nt

of

Pa

tie

nts

0.90.6

2.2

1.8

0.5

1.0

1.5

2.0

2.5

CV + DM DM

Pa

tie

nts

(M

M)

CADCEVD/PAD

PrimaryPrevention

Regulatory approval

Biomarker Effect

Type II Diabetes41% (36%)


47% (38%)

Coronary Artery Disease (CAD)66% (65%)


47% (38%)

Metabolic Syndrome37% (29%)


38% (32%)

Hypertension34% (28%)


54% (50%)

Regulatory approval

Epidemiological study: shown elevated disease biomarker

7.7MM to 8.7 MM total patients

0.71.1

3.02.8

0.5

1.0

1.5

2.0

2.5

Pa

tie

nts

(M

M)

0.8

1.3

3.23.43.0

CV + DM DM CAD/CEVD/PAD Primary Prev.

50%

36%

47%

30%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%


Pe

rce

nt

of

Pa

tie

nts 54%

41%

53%

36%

55%

CAD App & Epi

CAD App + Epi

Surrogate Effect

Type II Diabetes37% (36%)


46% (44%)

Coronary Artery Disease (CAD)71% (68%)


42% (39%)

Metabolic Syndrome33% (31%)


36% (34%)

Hypertension30% (29%)


61% (54%)

Regulatory approval

Epidemiological study: shown elevated disease biomarker

Study has shown improvement in surrogate endpoint

7.9MM to 8.4 MM total patients

54%

36%

50%

31%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%


Pe

rce

nt

of

Pa

tie

nts 61%

37%

53%

33%

55%

CAD App + Epi

CAD App + Epi + Surr in CV+DM

1.20.9

3.4

2.4

0.5

1.0

1.5

2.0

2.5

Pa

tie

nts

(M

M)

1.3

3.6

2.5

3.0


0.9

Primary Hypertension Treatment#

Type II Diabetes

US 56% (53%)EU 45% (50%)


US 64% (53%)EU 53% (50%)


US 79% (53%)EU 75% (50%)

Survey Responses

Client Estimate*

* Prescribing for secondary prevention patients with elevated BP is much higher (e.g., 85% for CAD patients with elevated BP in the U.S.).

# Physician responses for secondary prevention patients are weighted 2:1 cardiologist to PCP; for primary prevention, patients weighted 1:5 cardiologist to PCP.


US 63% (53%)EU 51% (50%)

Metabolic Syndrome

US 53% (69%)EU 51% (43%)


US 66% (69%)EU 62% (43%)

Hypertension

US 62% (69%)EU 57% (43%)


US 82% (53%)EU 81% (50%)

Halo Effect Summary

A B C D E F G H I J K L M N O

Scenario

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

Pati

en

ts (

MM

)

Indication Halo Biomarker Surrogate

Revenue Present Value versus Clinical Cost

Scenario A

Scenario B

Scenario C

Scenario D

Scenario E

Scenario F

Scenario G

Scenario H

Scenario I

Scenario J

Scenario K

Scenario L

Scenario M

Scenario N

Scenario O

Cost versus Revenue PV Index

50

60

70

80

90

100

$150 $200 $250 $300 $350

Clinical Development Cost

Re

ve

nu

e P

V I

nd

ex

(0

-1

00

)

Outcome◼ Phase IIB program to support the “Blue”

registration plan, which maximizes revenues and saves:• $80 million

• 1 year to market

◼ Technique recently expanded to marketed products-predicting impact of new(Phase IV) clinical trials• Client sponsored

• Competitor sponsored

Conclusions◼ MR spending early in development can

save $ and time

◼ “Rocket science” is understanding clinical trial trade offs, not MR tools

◼ Web enables more complex research• Faster and better, not

• Faster and cheaper

conference logo slide...european halo effect peripheral arterial disease (pad or pvd) 26% metabolic...

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