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John L. LaMattina, Ph.D.President, Worldwide Research
Pfizer Global Research and Development
John L. LaMattina, Ph.D.President, Worldwide Research
Pfizer Global Research and Development
Leveraging the Genome
Fact, Fiction, and Ethical Implications
Leveraging the Genome
Fact, Fiction, and Ethical Implications
WPI 3/2002
The Global R&D ChallengeThe Global R&D Challenge
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
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
WPI 3/2002
Lipid-Lowering Hypertension/Angina ArthritisDepression/Anxiety Antibiotic Erectile Dysfunction Seizure Disorders Antifungal Hypertension/BPHAlzheimer’s DiseaseAllergyCardiovascular
Lipid-Lowering Hypertension/Angina ArthritisDepression/Anxiety Antibiotic Erectile Dysfunction Seizure Disorders Antifungal Hypertension/BPHAlzheimer’s DiseaseAllergyCardiovascular
ProductsProducts CategoryCategory
NeurontinNeurontin
Accupril/AccureticAccupril/Accuretic
Major Internally Discovered ProductsMajor Internally Discovered Products
Broad Portfolio - Number 1 or 2 Broad Portfolio - Number 1 or 2
WPI 3/2002
A Research-Based Health Care Company
CompanyCompany
2000 Total R&D Spending($ Billions)
2000 Total R&D Spending($ Billions)
Aventis
Johnson & Johnson
Schering-Plough
4.4
3.8
2.9
3.2
Pfizer
Glaxo/SmithKline
1.3
Novartis
AstraZeneca
Roche
Merck
Bristol-Myers Squibb
Eli Lilly
American Home Products
2.7
2.6
2.42.3
2.0
2.0
1.7
WPI 3/2002
Administrative Support Analytical Chemistry Animal Health Anti-infective Disease Bacteriology
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 Employee Resources
Endocrinology Enzymology Facilities Maintenance Fermentation Finance Formulation
Gastroenterology Graphic Design Histomorphology Intestinal Permeability Law Library Science 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
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
Pharmaceutical R & D -A Multi-Disciplinary Team
Over 100Over 100DifferentDifferent
DisciplinesDisciplinesWorking TogetherWorking Together
WPI 3/2002
Development Process Starts with Many Hypotheses
AttenuateAttenuate NeuroNeuro--inflammationinflammation
Stop Programmed Cell DeathStop Programmed Cell Death
PreventPrevent AmyloidAmyloid Plaques Plaques
Block GlutamateBlock Glutamate NeurotoxicityNeurotoxicity
Stabilize Neuronal Infrastructure Stabilize Neuronal Infrastructure
Alzheimer’s DiseaseAlzheimer’s Disease
WPI 3/2002
DiscoveryDiscovery
Exploratory DevelopmentExploratory Development
Full Full DevelopmentDevelopment
RegistrationRegistration
Large Amounts ofCandidate Medicine
Synthesized
Project Teamand Plans Synthesis
of Compounds
EarlySafety
Studies
CandidateFormulations
Developed
ExtensiveSafety
Studies
Screening
Studies in HealthyVolunteers Phase I
Candidate Medicine Tested in3-10,000 Patients (Phase III)
Studies in 100-300Patients (Phase II)
Clinical DataAnalysis
The Long Road to a New Medicine
WPI 3/2002
High Risk Process: 11-15 Years, $800MM+
PreclinicalPharmacology
Preclinical Safety
Millions ofCompounds Screened
IdeaIdea DrugDrug11 - 15 Years
1 1 -- 2 2 ProductsProducts
DiscoveryDiscovery Exploratory DevelopmentExploratory Development Full DevelopmentFull Development
Phase I Phase II Phase III
00 151555 1010
Clinical Pharmacology& Safety
~100 Discovery Approaches~100 Discovery Approaches~100 Discovery Approaches
WPI 3/2002
Innovation Process Difficult
Complex Disease Targets
Too Long in Body
Adverse Reactions
Poor Absorption
Low Levels in Body
Not Effective Enough
Not Sufficiently Selective
Side Effects
Unsafe
Unstable
Competition
Impractical To Make
Most Most Compounds Compounds
Do Not BecomeDo Not BecomeMedicinesMedicines
WPI 3/2002
Consolidation TrendsConsolidation TrendsShrinking Ranks - 1988 PMA Members Still Independent
• Abbott Laboratories • G.D. Searle • Procter & Gamble• American Cyanamid • GlaxoSmithKline • Rhone Poulenc• American Home Products • Glaxo Wellcome • Rorer• A.R. Robins • Hoechst Marion Roussel • R.P. Scherer• AstraZeneca • Hoffman-LaRoche • Sandoz• Aventis • ICI Zeneca • Schering-Plough• Beecham Laboratories • Johnson & Johnson • SmithKline Beecham• Boehringer Ingelheim • Eli Lilly • Squibb• Boots Pharmaceuticals • Marion Laboratories • Sterling Drug• Bristol-Myers Squibb • Merck • Syntex• Carter-Wallace • Merrell Dow • Upjohn Company• Ciba Geigy • Novartis • Warner-Lambert• Connaught Laboratories • Pfizer • Wellcome• Fisons Corporations • Pharmacia
WPI 3/2002
Opportunity to Do Much MoreOpportunity to Do Much More
WPI 3/2002
Molecular Insights into Disease
Cell Chromosomes
DNA
GeneSwitch
Nucleotide Base Pairs
Protein
ReceptorsHormonesEnzymes
Nucleus
WPI 3/2002
What Are Practical Implications of Human Genome for Drug Development?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 expensiveNo guarantee that they will lead to new medicines
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 expensiveNo 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 - 2000Glucose transport and storage Signaling pathways - 2000
WPI 3/2002
Myths about Genomic InformationMyths about Genomic Information
It will lower the cost of drug developmentTechnology is expensiveMechanisms poorly understoodMore targets = More Cost
We can use it to develop “magic bullets”Chronic disease complicated, multifacetedMultiple genes frequently involvedEnvironment, behavior remain important
– Sometimes determinative
It will lower the cost of drug developmentTechnology is expensiveMechanisms poorly understoodMore targets = More Cost
We can use it to develop “magic bullets”Chronic disease complicated, multifacetedMultiple genes frequently involvedEnvironment, behavior remain important
– Sometimes determinative
WPI 3/2002
Ethical Issues of Genomic InformationEthical Issues of Genomic Information
Who owns the data?Government?Individuals?Companies?
Who Collects the data? Who pays?
How will the data be used?Insurance issuesPrivacy issuesDiscrimination
Who owns the data?Government?Individuals?Companies?
Who Collects the data? Who pays?
How will the data be used?Insurance issuesPrivacy issuesDiscrimination
WPI 3/2002
Ethical Issues: PatentsEthical Issues: Patents
Diamond v. Chakrabarty, 1980Biological organism can be patented
The Great Sequence HuntPositives - competition pushed sequencingNegatives - what value was created?
Recent RulingSequence not controlling, must have function
Diamond v. Chakrabarty, 1980Biological organism can be patented
The Great Sequence HuntPositives - competition pushed sequencingNegatives - what value was created?
Recent RulingSequence not controlling, must have function
WPI 3/2002
Example of Ethical Issues: SNP’sExample of Ethical Issues: SNP’s
Single nucleotide polymorphisms (SNP’s)Can identify individual risk profile for various diseasesCould be used to screen patients for clinical trials - improve safety
Broad screening can provide important insights into population genetics
Each individual could have “tailored” drugs
Single nucleotide polymorphisms (SNP’s)Can identify individual risk profile for various diseasesCould be used to screen patients for clinical trials - improve safety
Broad screening can provide important insights into population genetics
Each individual could have “tailored” drugs
WPI 3/2002
Example of Ethical Issues: SNP’sExample of Ethical Issues: SNP’s
Who should pay for the screening?Government?Private companies?
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?
Who should pay for the screening?Government?Private companies?
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?
WPI 3/2002
Some ThoughtsSome Thoughts
New Area of Ethical DiscussionNeed complete transparencyHIPPA rules promulgated, now to be implemented
Need “opt-in” system, not “opt-out”Presumption of privacy should be preserved
Education is critical - complex issues with many facets - public good versus private rights
Different cultural contexts must be respected
New Area of Ethical DiscussionNeed complete transparencyHIPPA rules promulgated, now to be implemented
Need “opt-in” system, not “opt-out”Presumption of privacy should be preserved
Education is critical - complex issues with many facets - public good versus private rights
Different cultural contexts must be respected
WPI 3/2002
Final ThoughtsFinal Thoughts
Genomic Technologies show great promise but require enormous resources.
Ethical Issues RealTransparent processes critical to public support
Support for Research CriticalPrice Control Threats
We Can’t Do it Alone
Genomic Technologies show great promise but require enormous resources.
Ethical Issues RealTransparent processes critical to public support
Support for Research CriticalPrice Control Threats
We Can’t Do it Alone
WPI 3/2002
Extending our Web of AlliancesExtending our Web of Alliances
XX--RayRayUTHSUTHS
TransTrans--genicsgenics HumAbHumAb
ChipChipTechnologyTechnology
MolecularMolecularModelingModeling
GeneGeneTherapyTherapy
GenomicsGenomics ChemicalChemicalDiversityDiversity
CombinaCombina--torialtorial
LibrariesLibraries
Mass. Mass. GeneralGeneral CornellCornell
Univ.Univ.
HarvardHarvard
YaleYale
MITMIT
Washington Washington Univ.Univ.
RockefellerRockefellerUniv.Univ.
Univ. ofUniv. ofWashingtonWashington
RigeRigell
IBISIBIS
NeurogenNeurogen
CeleraCelera
EvotecEvotec IncyteIncyte
XenonXenon
ArQuleArQule
AuroraAurora
AbgenixAbgenix
JohnsJohnsHopkinsHopkins
WPI 3/2002
SummarySummary
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 everPrice controls in the US would devastate innovation
Good public health is expensive, and worth it
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 everPrice controls in the US would devastate innovation
Good public health is expensive, and worth it