Transcript Pharmaceutical Products R&D Pipeline

Leveraging the Genome
Fact, Fiction, and Ethical
Implications
John L. LaMattina, Ph.D.
President, Worldwide Research
Pfizer Global Research and Development
1
The Global R&D Challenge
WPI 3/2002

One Pill Must Be Globally Safe and Efficacious
– Across Racial and Ethnic Groups
– Across Age, Weight, and Sex Differences

One Pill Must Appeal to Global Markets
– Different Cultures, Healthcare systems,
Distribution systems

One Pill to Pass Global Regulatory Review
– MOST Regulated Industry in the World
– Must meet regulatory requirements in
EVERY country
Broad Portfolio - Number 1 or 2
Major Internally Discovered Products
Products
Category
Lipid-Lowering
Hypertension/Angina
Arthritis
Depression/Anxiety
Antibiotic
Erectile Dysfunction
Neurontin
Seizure Disorders
Antifungal
Hypertension/BPH
Alzheimer’s Disease
Allergy
Accupril/Accuretic
WPI 3/2002
Cardiovascular
A Research-Based Health Care Company
Company
4.4
Pfizer
3.8
Glaxo/SmithKline
3.2
Aventis
2.9
Johnson & Johnson
2.7
Novartis
2.6
AstraZeneca
Roche
2.4
2.3
Merck
Bristol-Myers Squibb
2.0
Eli Lilly
American Home Products
Schering-Plough
WPI 3/2002
2.0
1.7
1.3
2000 Total R&D Spending
($ Billions)
Pharmaceutical R & D A Multi-Disciplinary Team
Administrative Support Analytical Chemistry Animal Health Anti-infective Disease Bacteriology
Over 100
Different
Behavioral Sciences Biochemistry Biology Biometrics Cardiology Cardiovascular Science Clinical Research
Communication Computer Science Cytogenetics Developmental Planning DNA Sequencing Diabetology
Document Preparation Dosage Form Development Drug Absorption Drug Degradation Drug Delivery
Electrical Engineering Electron Microscopy Electrophysiology Environmental Health & Safety
Endocrinology Enzymology Facilities Maintenance Fermentation Finance
Employee Resources
Formulation
Gastroenterology Graphic Design Histomorphology Intestinal Permeability Law Library Science
Disciplines
Medical Services
Mechanical Engineering Medicinal Chemistry Molecular Biology Molecular Genetics Molecular Models
Natural Products Neurobiology Neurochemistry Neurology Neurophysiology Obesity
Oncology Organic Chemistry Pathology Peptide Chemistry Pharmacokinetics Pharmacology Photochemistry
Working Together
Physical Chemistry Physiology Phytochemistry Planning Powder Flow Process Development
Project Management Protein Chemistry Psychiatry Public Relations Pulmonary Physiology
Radiochemistry Radiology Robotics Spectroscopy Statistics Sterile Manufacturing Tabletting Taxonomy
Technical Information Toxicology Transdermal Drug Delivery Veterinary Science Virology X-ray Spectroscopy
WPI 3/2002
Development Process Starts with Many
Hypotheses
Prevent Amyloid Plaques
Block Glutamate Neurotoxicity
Attenuate Neuro-inflammation
Stabilize Neuronal Infrastructure
Stop Programmed Cell Death
Alzheimer’s Disease
WPI 3/2002
The Long Road to a New Medicine
Registration
Clinical Data
Analysis
Full
Development
Studies in 100-300
Patients (Phase II)
Candidate Medicine Tested in
3-10,000 Patients (Phase III)
Large Amounts of
Candidate Medicine
Synthesized
Extensive
Safety
Studies
Studies in Healthy
Volunteers Phase I
Exploratory Development
Project Team
and Plans
WPI 3/2002
Candidate
Formulations
Developed
Early
Safety
Studies
Synthesis
of Compounds
Screening
Discovery
~100 Discovery Approaches
High Risk Process:
11-15 Years, $800MM+
Millions of
Compounds Screened
Preclinical
Pharmacology
Preclinical Safety
1-2
Products
Clinical Pharmacology
& Safety
Discovery
Exploratory Development
Phase I
0
Phase II
WPI 3/2002
Phase III
10
5
Idea
Full Development
11 - 15 Years
15
Drug
Innovation Process Difficult
Complex Disease Targets Not Sufficiently Selective
Most
Too Long in Body
Side Effects
Adverse Reactions Compounds
Poor Absorption Do
Low Levels in Body
WPI 3/2002
Not Become
Medicines
Not Effective Enough
Unsafe
Unstable
Competition
Impractical To Make
Opportunity to Do Much More
WPI 3/2002
Molecular Insights into Disease
Nucleus
Cell
Chromosomes
Nucleotide Base Pairs
DNA
Switch
Gene
Protein
Hormones
Enzymes
Receptors
WPI 3/2002
What Are Practical Implications of
Human Genome for Drug Development?

Increase in targets from ~ 450 to > 4000.

Can Focus on Human Receptors, Ligands.

Potentially develop more specific medicines.

However:
 Exploring New Mechanisms takes time and $
 New Technologies are very expensive
 No guarantee that they will lead to new
medicines
WPI 3/2002
Implications of the Genome:
Insulin Signaling - 1977
WPI 3/2002
Glucose transport and storage Signaling pathways - 2000
WPI 3/2002
Myths about Genomic Information

It will lower the cost of drug development
 Technology is expensive
 Mechanisms poorly understood
 More targets = More Cost

We can use it to develop “magic bullets”
 Chronic disease complicated, multifaceted
 Multiple genes frequently involved
 Environment, behavior remain important
– Sometimes determinative
WPI 3/2002
Ethical Issues of Genomic Information

Who owns the data?
 Government?
 Individuals?
 Companies?

Who Collects the data? Who pays?

How will the data be used?
 Insurance issues
 Privacy issues
 Discrimination
WPI 3/2002
Ethical Issues: Patents

Diamond v. Chakrabarty, 1980
 Biological organism can be patented

The Great Sequence Hunt
 Positives - competition pushed sequencing
 Negatives - what value was created?

Recent Ruling
 Sequence not controlling, must have function
WPI 3/2002
Example of Ethical Issues: SNP’s

Single nucleotide polymorphisms (SNP’s)
 Can identify individual risk profile for various
diseases
 Could be used to screen patients for clinical
trials - improve safety
WPI 3/2002

Broad screening can provide important
insights into population genetics

Each individual could have “tailored” drugs
Example of Ethical Issues: SNP’s

Who should pay for the screening?
 Government?
 Private companies?
WPI 3/2002

Once you have broadly screened the
population, what is societal obligation to treat?

Should you screen for diseases for which there
is no cure? (Huntington’s, e.g.).

What about “artificial” selection?
Some Thoughts

New Area of Ethical Discussion
 Need complete transparency
 HIPPA rules promulgated, now to be
implemented

Need “opt-in” system, not “opt-out”
 Presumption of privacy should be preserved
WPI 3/2002

Education is critical - complex issues with
many facets - public good versus private rights

Different cultural contexts must be respected
Final Thoughts

Genomic Technologies show great promise but
require enormous resources.

Ethical Issues Real
 Transparent processes critical to public support

Support for Research Critical
 Price Control Threats

WPI 3/2002
We Can’t Do it Alone
Extending our Web of Alliances
IBIS
Mass.
General
Washington
Univ.
Cornell
Univ.
X-Ray
Aurora
Transgenics
Abgenix
Yale
Neurogen
HumAb
UTHS
Gene
Therapy
Chip
Technology
Harvard
Rige
l
ArQule
Rockefeller
Univ.
Molecular
Modeling
Xenon
Celera
Univ. of
Genomics Washington
Evotec
WPI 3/2002
Incyte
Chemical
Diversity
Combinatorial
Libraries
Johns
Hopkins
MIT
Summary

Genomics will play an important role in
developing new medicines

Costs will increase, at least in the short term

Ethical issues daunting

Support for R&D more critical than ever
 Price controls in the US would devastate
innovation

WPI 3/2002
Good public health is expensive, and worth it