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PHARMACEUTICAL VALUE

CREATION

John W. Medcof, PhD

DeGroote School of Business









1

lect07 pharma 2008 02 01

PHARMACEUTICAL

VALUE CREATION



1.0 Introduction -ICE

2.0 The Industry

3.0 The Pipeline

4.0 Biotechnology and Outsourcing





2

lect07 pharma 2008 02 01

IC♦E

The Technology Commercialization Value Chain



BUSINESS STRATEGY





I C E

INVENT CREATE EXTRACT

Technologies with Commercial Value Commercial Value

Potential In technologies From technologies

Commercial Value





DECISION DECISION

1 2







MANAGEMENT PROCESSES

3

lect07 pharma 2008 02 01

2.0 THE INDUSTRY



Global Pharmaceutical Markets

• Canada $US 8.6B 1.9 %

• Europe $US 116 B 27.0 %

• Japan $US 49 B 11.5 %

• Asia/Africa $US 34B 8.0 %

• Latin America $US 16B 3.4 %

• US $US 295 B 48.2 %

• Total $US 432 B 100.0 %



4

lect07 pharma 2008 02 01

Top Global Pharmaceuticals

(S&P 2003)



• Company Sales ($US B)

• Pfizer 28.28

• GSK (Glaxo-SmithKline) 28.20

• Merck 21.63

• Astrazeneca 17.84

• Aventis 17.25

• Johnson & Johnson 17.20

• Novartis 15.36

• Bristol-Myers Squib 14.70

• Pharmacia 12.03

• Wyeth 11.70

5

lect07 pharma 2008 02 01

Locations of Top 50 Pharma Companies



1





12





20









17









USA Europe Japan Isreal







6

lect07 pharma 2008 02 01

Top 20 Companies by Pharma Sales

(2002 in Canada – IMS)





• Pfizer $ 1300 M • Aventis $ 449 M

• GSK $ 1044 M • Wyeth $ 443 M

• Merck Frosst $ 950 M • Lilly $ 408 M

• AstraZeneca $ 891 M • Schering-Plough $ 331 M

• J&J $ 703 M • Roche $ 322 M

• Apotex $ 644 M • Bayer $ 299 M

• Pharmacia $ 542 M • Novopharm $ 255 M

• BMS $ 529 M • Genpharm $ 214 M

• Novartis $ 503 M • Ratiopharm $ 199 M

• Abbott $ 487 M • Pharmascience $ 191 M







7

lect07 pharma 2008 02 01

Top 5 Products in Canada by Sales

(2002 - IMS)

• Lipitor (Pfizer) $ 625 M Cholesterol

• Losec (AstraZeneca) $ 424 M GI anti-ulcer

• Zocor (Merck Frosst) $ 291 M Cholesterol

• Norvasc (Pfizer) $ 250 M Cardiovasc.

• Altace (Wyeth) $ 234 M Cardiovasc.





8

lect07 pharma 2008 02 01

Big Generics Players in Canada





• Apotex and Novopharm (Teva) are the 2 largest

generic manufacturers in Canada

– Account for for more than half of generic market

• Apotex (Canadian owned) is also the top spender of

R&D in the pharmaceutical industry in Canada

– In front of Pfizer, GSK and Mercka

• Both companies also have many international ties

that allow for significant economies of scale

a - “Canada’s Top 100 Corporate R&D Spenders, 2003”

http://www.researchinfosource.com/top100.shtml







9

lect07 pharma 2008 02 01

What is a a generic drug?





• Low cost version of a brand name drug

• Must be approved by Health Canada

• There is no difference in quality, purity,

effectiveness and safety

• Said to be bioequivalent

• Fillers may be different



10

lect07 pharma 2008 02 01

Costs for Canadians









11

lect07 pharma 2008 02 01

http://imshealthcanada.com/htmen/3_2_19.htm

Aggregate Sales Growth

Rx&D vs. Generics (1988-2000)

$1.4 billion

600% Rx&D

544%

Generics

500%



400%



300%

187%

200%

$295 million

100%



0%

87



88



89



90



91



92



93



94



95



96



97



98



99



00

19



19



19



19



19



19



19



19



19



19



19



19



19



20

(C-22) (C-91)





Source: IMS Canada

12

lect07 pharma 2008 02 01

3.0 THE PIPELINE









13

lect07 pharma 2008 02 01

New Drug Development Process









14

lect07 pharma 2008 02 01

The Pipeline Phases



• Basic R&D and Discovery

• Pre-Clinical Phase

• Clinical Trials

• Regulatory Approval





15

lect07 pharma 2008 02 01

Basic R&D and Discovery



• Library

• Screening

• Tweaking (Lead Compound)









16

lect07 pharma 2008 02 01

Pre-Clinical Phase

Pre-Clinical Trials (Lead Compound Evaluation)



Toxicity

Bioavailability

Pharmacokinetics

Efficacy



17

lect07 pharma 2008 02 01

Clinical Trials



• Phase 1: Safety

• Phase 2: Efficacy and safety in patients

(small numbers)

• Phase 3: Efficacy and safety in patients

(large numbers)





18

lect07 pharma 2008 02 01

Regulatory Approval



• New Drug Submission (NDS) application

• Notice of Compliance (NOC)









19

lect07 pharma 2008 02 01

Important Regulatory Bodies in

Canada

TPD - Therapeutic Products Directorate

BGTD - Biologics and Genetics Therapeutic

Directorate

CDR - Common Drug Review

PMPRB - Patented Medicines Pricing and

Review Board

Formularies

20

lect07 pharma 2008 02 01

The Formularies



The formularies are lists created by the

provinces and territories which indicate

which medications they will pay for and

how much. They may include other rules

about priorities and special

circumstances.



21

lect07 pharma 2008 02 01

Pipeline Dynamics





• Time

• Money

• Hit Rate: 1:10,000

• The full pipeline





22

lect07 pharma 2008 02 01

TIME



New Drug Development Process

Preclinical Development Clinical Development



Regulatory Approval Effective Patent Term









Patent 20

3-4 8 10*

Year 0



* Average year for market entry, individual products can vary.







23

lect07 pharma 2008 02 01

Rx&D Companies’ New Drug Submissions

(Average Time to Approval)

1400

1163 1142

1200 1097 1089 1044

1024 1045

1000 940



800 682 743 717

615 549

570 591

600

400

200

0

87

88

89

90

91

92

93

94

95

96

97

98

99

00

01

19

19

19

19

19

19

19

19

19

19

19

19

19

20

20

Source: Rx&D Notice of Compliance Survey (2001) - compiled by KPMG.



24

lect07 pharma 2008 02 01

Effective Patent Life of an

Innovative Pharmaceutical Product

Canada

Brazil

Mexico

United States of America

Japan

Europe*



0 5 10 15 20



* Includes all member States of the European Union + Finland, Sweden, Switzerland, and Norway.



25

lect07 pharma 2008 02 01

MONEY: Estimated Cost of

Bringing a New Drug to

Market

$900 $802

$800

$700

$US Millions









$600 $500

$500

$400

$231

$300

$125

$200 $54

$100

$0

1976 1986 1987 1995 2001



Source: University of Rochester, Texas A&M University, Tufts University, Tufts Center for

the Study of Drug Development 2001, US Congress Office of Technology Assessment .

26

lect07 pharma 2008 02 01

Ratio of Canadian Prices to

Median International Prices

(1987-2001)

1.4 1.23

1.17 1.13 1.14 1.11

1.2 1.08 1.08

0.99

0.93 0.9 0.92 0.95

1 0.89 0.88 0.89



0.8

Ratio









0.6

0.4

0.2

0

87



88



89



90



91



92



93



94



95



96



97



98



99



00



01

19



19



19



19



19



19



19



19



19



19



19



19



19



20



20

Source: PMPRB Annual Report, 2001. Beginning in 1999, the

ratio includes prices of patented drugs for human use only.

27

lect07 pharma 2008 02 01

HIT RATE: Probability of

NCE Success at Each Stage









28

lect07 pharma 2008 02 01

The Full Pipeline



Products in Pipeline – Globally



• Pre-clinical: 3249

• Phase 1: 648

• Phase 2: 864

• Phase 3: 258

• Pre-reg/Reg: 102

• Total: 5121



Biotech Products represent 24 % of Pipeline

29

lect07 pharma 2008 02 01

Pre- and Post-Pipeline Issues





• Pre-Pipeline Issues

• Post-Pipeline Issues









30

lect07 pharma 2008 02 01

4.0 Biotechnology & Outsourcing









31

lect07 pharma 2008 02 01

Biotech Industry Role in New Drug

Discovery

• New Drug Development process is hugely

expensive

• Biotech firms have radically impacted this

process

• Biotech firms typically remain small and

non-vertically integrated operations

• How have they been successful?

32

lect07 pharma 2008 02 01

Two Keys to Success



• Technology innovation in drug discovery

– Molecular modeling & rational drug design



• Hub in a network of Strategic Alliances to

efficiently bring a compound to market

– University Labs/Research Centres

– Big Pharma Partnerships

33

lect07 pharma 2008 02 01

Biotech & Big Pharma Alliance

Pharma Environment Biotech Environment

• Bureaucratic • Entrepreneurial, Faster, Flexible

• Price pressure in Canada • Access to university resources

& federal funding

• Intolerance for branded “me too”

• Specialists in a therapeutic

products class

• Generic pressure • Need capital to move from

• Increasing cost of innovation discovery to development

methods • Need resources (sales,

• Money & muscle in regulatory, marketing, distribution)

distribution, sales & marketing







34

lect07 pharma 2008 02 01

Biotech & Pharma in NDD

• Biotech key competency in Discovery

• Development requires huge resources

– Regulatory

– Clinical Trial

• Biotech can either go public or form partnerships

to commercialize compound









35

lect07 pharma 2008 02 01

The Move to External Sourcing



• Big Pharma is vertically integrated firms

• Biotechs lead the way

• New technologies / new niches

– Combinatorial Chemistry

– Software “individuals”

• The Rise of External Sourcing and CRO’s



36

lect07 pharma 2008 02 01



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