Transcript No Slide Title

What Have We Not Discussed?
The Next Steps Toward The Clinic
ASENT: February 25, 2012
Roger J. Porter, M.D.
Consultant
Chief Scientific Officer, ETP
Adjunct Professor of Pharmacology, USUHS
Adjunct Professor of Neurology, Univ. of Pennsylvania
Former Deputy Head, CR&D, Wyeth-Ayerst Research
Former Deputy Director, NINDS, NIH
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The Process of Discovery and Development
BASIC
RESEARCH
(Discovery)
Government
• NIH
Private Sector
• Biomedical
Research
Companies
• Non-Profit
Foundations
TRANSLATIONAL
RESEARCH
Knowledge
About
Disease
APPLIED
RESEARCH
(Development)
Government
• NIH
Private Sector
• Biomedical
Research
Companies
Private Sector
• Biomedical
Research
Companies
Consumers
Cures,
Treatments,
and
Prevention
• Non-Profit
Foundations
Source: FDA Council Congressional Briefing Series, “Molecules to Miracles,” 1997.
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COMMENT: The Overall Process
• Everybody is doing everything
• Example: Substantial Activity from Non-Profits
in all Areas of Neurological Research
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Non-Profit Contributions to Research
in Neurologic Disorders
Annual $$ in Grants from IRS 990
Multiple Sclerosis Society: $32M (2009)
Muscular Dystrophy Assn.: $49M (2010)
Parkin. Dis.---2 orgs+MJF: $56M (2009-10)
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Molecular Opportunity
Project Initiation
Market Opportunity
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COMMENT: The Market
• Think About The Market Early In The Process
Of Drug Development—
- Will The Intellectual Property Of The
Compound Be Sufficient To Attract A
Company?
- If The Intellectual Property Is Weak, Is There
An Alternate Path?
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DRUG PRODUCT FLOW
Discovery
Lead
Finding
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IND
Track
Development
Phase
I
Phase
II
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Phase
III
Registration
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(DISCOVERY)
PHARMACEUTICAL DEVELOPMENT
MEDICINAL CHEMISTRY
DRUG METABOLISM
DRUG SAFETY
REGULATORY INPUT
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DRUG PRODUCT FLOW
Discovery
Lead
Finding
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IND
Track
Development
Phase
I
Phase
II
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Phase
III
Registration
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Phase I
The first 2-3 studies in humans.
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COMMENT:Phase I
--A stage of drug development
--Sometimes erroneously used to describe
the Clinical Pharmacology studies which are
performed throughout the entire period of
the drug’s development.
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Typical Phase I Studies
1) Single Ascending Dose (SAD)
---also usually the “FIM”
2) Multiple Ascending Dose (MAD)
----------------------------------3) Effect of Food (Prelim)
4) Effect of Age and/or Gender (Prelim)
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Additional Studies Performed by
Clinical Pharmacology
1) Are performed throughout development
2) Include: drug interactions, dose
proportionality, renally impaired, hepatically
impaired, bioequivalence/bioavailability,
mass balance, etc.
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DRUG PRODUCT FLOW
Discovery
Lead
Finding
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IND
Track
Development
Phase
I
Phase
II
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Phase
III
Registration
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Phase II
Is The Drug Effective at a Safe Dose?
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205-EU/AU/US : Study Design
mg
1200
1200
Optional LongTerm extension
study
or
1100
1050
1000
900
900
800
750
700
600
600
Tapering
500
450
400
300
Placebo
0
-56
1
Screening
Seizure Baseline
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8 15
22
29 36
Titration
43
50
113
57
Maintenance
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148
Interim
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168 Days
Taper
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COMMENT:
The Federal Government is Much
Less Efficient Than The Industry In
the Conduct of Clinical Trials!
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Phase III
Is The Drug Safe and Effective in a
Larger Population?
--For Drugs, Typically 2 RCCTs
--For Devices, Typically 1 RCCT
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NO COMMENT
Phase III is hard work
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Regulatory
Process
How Long Does It Really Take To Get
Regulatory Approval?
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COMMENT
Is The Regulatory Process Broken?
Ezogabine (Retigabine)
Filed (FDA accepted) December,2009
Approved in Europe in March, 2011
DEA approval this week?
NeuroPace RNS System
Filed (FDA accepted) Nov, 2010
Adv Comm Mtg not yet scheduled
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Neurological
Science and New
Therapies
In Spite of All These Hurdles, We Are
Making Slow But Steady Progress
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STOP!
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PHARMACEUTICAL R&D
IN THE NEW MILLENNIUM
OPPORTUNITY
CHALLENGE
•
Scientific and Medical
Breakthroughs
•
•
Technology Breakthroughs
Complexities of Scientific
Environment/Regulatory
Hurdles
•
Cost Containment
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
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Issues Affecting The Pharma Industry
Legislation &
Regulation
Mergers &
Acquisition
Access to Medicines
(Medicare)
Liability
&
Litigation
Pricing
Intellectual
Property Protection
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Patient Privacy
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Number of Compounds in
Development (Clinical-Preregistered)
Late-Stage Pipeline - U.S. Leads the World
3000
2500
104%
increase
in U.S.
2000
1500
US
Rest of World
EU
Japan
1000
500
0
1997
1999
2001
2003
2005
Year
Source: Adis R&D Insight Database, customized run, December 2005.
Notes: Comparisons for were completed for June of each year. Some compounds will be at different phases for
different indications.
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Drop in Death Rate for Diseases Treated
with Pharmaceuticals 1965-1996
Disease
Treatment
Rheumatic Fever
and Rheumatic
Heart Disease
Antibiotics
Atherosclerosis
83%
ACE inhibitors, beta blockers, nitrates
Ulcer of Stomach
and Duodenum
74%
H2 blockers, proton pump inhibitors
0%
10%
20%
30%
40%
50%
72%
60%
70%
80%
90%
Percent Drop in Age-Adjusted Death Rate
Source: PhRMA, 1998, based on Boston Consulting Group, 1993, and U.S. National Center for Health Statistics, 1998
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Hepatitis A Incidence Falls to Historic
Lows with Increased Use of Vaccine
In 1999, it was recommended that children in 17 states with higher than average hepatitis A
incidence be vaccinated routinely.
Drop in incidence
States NOT Routinely
Vaccinating Children
↓ 53%
States Routinely Vaccinating
Children
↓ 88%
Overall
↓ 76%
A. Wasley, T. Samandari, B.P. Bell, “Incidence of Hepatitis A in the United States in the Era of Vaccination,”
Journal of the American Medical Association, 294 (2005): 2, 194-201.
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70
65
Recent study found that
new drugs account for
50-60% of the increase
in six-year cancer
survival rates since
1975.*
60
55
50
45
40
35
1997
1995
1993
1991
1989
1987
1985
1983
1981
1979
1977
30
1975
Percent of patients who survive 5 years
Cancer Survival Increasing
*F.R. Lichtenberg, “The Expanding Pharmaceutical Arsenal in the War on Cancer,” National Bureau of Economic Research Working Paper
No. 10328 (Cambridge, MA: NBER, February 2004).
National Cancer Institute, National Institutes of Health, Department of Health and Human Services, “Cancer Trends
Progress Report – 2005 Update,” (Bethesda, MD: NCI, December 2005), http://progressreport.cancer.gov/
(Accessed 26 January 2006).
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Investment in Research and Development Continues
to Grow
Expenditures (Billions of Dollars)
$60
$50
$40
PhRMA Member Companies' R&D
Expenditures
$51.3(est.)
$47.6
$37.0
Biopharmaceutical R&D Expenditures *
$30
(est.)
$39.4
$26.0
$20
$15.2
$8.4
$10
$2.0
$4.0
$0
1980
1985
1990
1995
2000
2004
2005
Sources: Burrill & Company, analysis for Pharmaceutical Research and Manufacturers of America, 2006.
PhRMA Annual Member Survey.
* Note: The “Biopharmaceutical R&D” figures include PhRMA research associates and non-members, which are not included in
“PhRMA Member Companies’ R&D Expenditures”. The first year this data was reported by PhRMA was 2004.
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Components of The
Pharmaceutical Industry
Biotech
• Venture Funded
Companies
- Based on New
Science/Technology
- Strong R&D
Emphasis
• Product Discovery &
Early Development
Stage Focus
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Big Pharma
• Generally Large Companies
- Small Number
- Established Products
• Fully Integrated
- Research &Development
- Manufacturing/Distribution
- Sales/Marketing
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TYPICAL ORGANIZATION OF A
PHARMACEUTICAL COMPANY
President
R&D
Discovery
Drug Metabolism
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Drug Safety
Pharmaceutical
Sciences
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Clinical
Research
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Regulatory
Affairs
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Quality Assurance
33
RESEARCH AND DEVELOPMENT
CONSIDERATIONS:
• What are the Strengths and
Weaknesses of the Organization?
• How Innovative Can We Be?
• How Innovative Can We Afford to Be?
• How Much Risk is Management
Willing to Take?
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Molecular Opportunity
Project Initiation
Market Opportunity
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Record of Invention

Biological Lead

Pharmacological Lead

IND Track (Clinical Lead)
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Biological Lead
Chemical Development
Efficiency of
Synthesis
Kg Batches
Suppliers
For
Who Can
Toxicology
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Make It
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THE MEDICINAL CHEMIST:
• Vary Greatly in their Innovative,
Goal-Oriented Capacity
• May Well Determine the Differences
Between Failure and Success
• Can Always Propose More Structures that
they Can Actually Create
• Combination of Imagination and Focusing
is Required
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DRUG METABOLISM
• Animal Studies:
- Make a Simple Assay
- Look at Kinetics in Rats, Dogs (Absorption and
Distribution
- Look for Toxicokinetics
- Look for Effect of Food, First Pass Metab,
Formulation Effect, Sex Effect
- C14 to Evaluate Metabolites (Rats and Dogs)
- ADME
- Cytochrome P450 Studies
- Develop a Clinical Analytical Method
• Clinical Studies
- Tox Support
- Clinical Support
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DRUG SAFETY STUDIES:
• Pilot Tox-Screen, Seek Target Organ
• 2 Week Studies-Dose Ranging (Rats and Dogs)
• 4 Week Studies-Allows for 2 Weeks in Man (101,102)
• Gentox
• Reproduction Studies
- Seg l Fertility
- Seg ll Fetal Tox
- Seg lll Perinatal and Developmental Defects
• 3 Month Studies (Could Be Extended to 6-12 Mos)
• Carcinogenicity Studies
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IND
Investigational New Drug (application)
--Results of all preclinical work
--Chemical structure
--Mechanism of action (if known)
--Adverse effects in animal studies
--How the compound will be
manufactured
--Clinical Plan and first protocol
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AT THE CLINICAL DEVELOPMENT
STAGE, THE TWO MOST
IMPORTANT FACTORS ARE:
1. The Therapeutic Improvement Offered by
the Product
2. The Order of Its Entry Into the Marketplace
of Similar
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DEVELOPMENT PROJECTS PRIORITY IN DESCENDING ORDER:
1. The Product is of a New Therapeutic Class and is First
to the Marketplace
2. The Product Is Not the First of the Class, But is
Significantly Better Than Other Therapies
3. The Product Is the Second to be Marketed, Either in a
New Therapeutic Class (#1 Above) or in a Category of
Improvement (#2 Above)
4. The Product Provides Only a Minor Improvement Over
Existing Therapy in Efficacy, Safety or Convenience
b. Adds No Value
5. The Product is Third of Fourth to the Market
6. The Product Offers No Improvement Over Existing
Therapy and is Late to the Marketplace
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TYPICAL ORGANIZATION OF A
CLINICAL RESEARCH DEPARTMENT
Senior V.P.
Clinical Research
Clinical
Pharmacology
Cardiovascular
Disease
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Central Nervous
System Diseases
Women's
Health
Infectious
Disease
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Oncology
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Immunology
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44
Aims of Phase I Studies
1) To define the acute and subacute
tolerability and toxicity of the drug at
various exposure levels in humans.
--intensive, in-patient, small no’s.
2) To define, inasmuch as possible, the
desired pharmacologic action of the drug
(efficacy)
3) To collect pharmacokineic information
and to correlate this informationt with both
the toxicity and the desired action of the
drug.
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Determining
Tolerability and Toxicity
Toxicity Evaluations Include:
-Intensity
-Duration
-Degree of Reversibility
---all as a function of dose and duration of
dosing
---usually in normal human volunteers
---the MTD is usually sought
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Determining
The Desired Pharmacological Effect
Efficacy evaluation requires a specific
response which is expected from the
mechanism of action of the drug is both:
1) Predictive of the Therapeutic Effect
and
2) Readily Assessable
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Determining
The Pharmacokinetic Profile
Pharmacokinetic Information can provide
data on:
•Absorption (w/wo food)
•Distribution
•Metabolism (if expected metabolites are already identified)
•Elimination
•--Relationship of above to dose (linearity)
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Summary:
Aims of The Phase I Program
To provide information for the rational
design of Phase II dose-response trials-specifically:
• Selection of doses for optimal dose
response
• Development of a safety monitoring
strategy
• Optimization of dosing in relation to meals
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One Example
of a Phase I Program
Retigabine--an antiepileptic drug
(from published data)
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Retigabine
H
H
N
N
F
NH2
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Retig--13008
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O
O
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Retigabine is Effective in the Following Models
of Epilepsy:
1. Maximal electroshock
2. Pentylenetetrazol
3. Picrotoxin
4. Kainate
5. Audiogenic
6. Corneal kindling
7. Cortical penicillin
8. Kindling development
9. Fully-kindled
Retigabine is Ineffective in the Following Models
of Epilepsy:
1. Voltage-dependent sodium channels
2. Calcium channels
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Retig--13004
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Retigabine
OpensOPENS
KCNQ2/3KCNQ2/3
Potassium
RETIGABINE
Channels
POTASSIUM CHANNELS
Retigabine
10 M
0.5 nA
1s
Induced current (x-fold)
Concentration-Response
5.0
4.0
3.0
2.0
1.0
EC50 = 1.7 µM
0.0
CHO cells expressing KCNQ2/3, voltageclamped at -50 mV.
0.1
1
10
100
Retigabine [µM]
Retigabine shifts the KCNQ2/3 activation V1/2 ~ -20 mV.
Retigabine shifts the KCNQ2/3 activation V1/2 ~ -20 mV.
Rundfeldt and Netzer, Neuroscience Letters
(17Mar2000)
282: 73-76.
Rundfeldt
and Netzer,
Neuroscience Letters (17Mar2000) 282: 73-76.
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Retigabine: Some of the more
important Clinical Pharmacology
studies completed
• Single-dose Tolerance : 100-GE (12)
• Multiple-dose Tolerance : 101-GE (46)
• Multiple-dose Tolerance : 102-US (40)
• Age gender : 105-EU (48)
• Food interaction : 106-EU (24)
• Dose Titration Tolerance : 107-US (9)
• Mass balance : 108-US (6)
• Lamotrigine interaction : 109-US (29)
• OC interaction : 112-US (16)
• Phenobarbital interaction : 113-US (15)
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Retigabine Phase I Results
Tolerability and Toxicity
• MTD was achieved in normal volunteers
• MTD was achieved in patients
• Adverse effects were largely CNS
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Retigabine Phase I Results
Desired Pharmacologic Effect
• Mechanism of action less well defined
• Cannot measure either seizure frequency
or a surrogate in normal volunteers.
• Only reliable measure of the desired
pharmacologic effect (efficacy) is RCCT.
• Phase I cannot contribute data to support
the desired pharmacologic effect (efficacy)
in this case
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Retigabine Phase I Results
Pharmacokinetics
Pharmacokinetics well defined
•Rapid and almost complete absorption
•Dose proportional
•No self induction or inhibition
•T 1/2 of 6-8 hours
•Oral clearance of 0.7L/hr/kg
•No significant drug interactions
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CONCLUSION:
Phase I Studies
How well does Phase I measure?
 Tolerability and toxicity
 Desired pharmacologic effect
(efficacy)
 Pharmacokinetics
How well does Phase I prepare the
investigator for Phase II?
 Selection of doses
 Safety monitoring strategy
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Phase II
• Controlled clinical trials (randomized, blinded, etc)
• Typically 100-500 patients with disorder
• Biggest goal is proof of concept
• Second biggest goal is dose determination
• Critical are the categorization of the adverse effects
• Also: dosing schedule
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202-US, MTD Study :
60 pts., Open Label
Background Medication
Carbamazepine, Phenytoin,
Topiramate or Valproate.
PK
Retigabine
PK
Tapering
Background
Medication
PK
PK
PK
PK
Baseline
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Titration
MTD
Add-on
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Retigabine
Monotherapy
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Retigabine Phase II Study
• Three doses versus placebo
• Add-on to other drugs
• 397 patients randomized
• 400 mg t.i.d. maximum dose
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Phase III
Controlled clinical trials
Larger number of patients
- Sometimes 1000-5000
May involve hospitals, clinics, physician offices
Object: Confirm effectiveness & confirm knowledge of
adverse effects
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Parallel to Phase III
• Ongoing toxicity tests
• Dosage forms
• Production scale-up
• Package design
• Begin preparation for NDA
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NDA
• New Drug Application (FDA)
• Analysis of all data is complete
• Drug is safe and effective
• All data submitted to the FDA (or other foreign
agency)
(May require a big truck)
• Wait for questions
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NDA Review/Approval
• FDA scientists review all the data
• May require an Advisory Panel review
• “Cleared for Marketing” means it is now available
--FDA took an average of 16.9 months in 2003*
--Rejected applications stable at 10-15%*
*PhRMA, 2007
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Post-Marketing Events
Monitoring is critical
--e.g, felbamate
--periodic reports to the agencies
Additional Studies may be required by agencies
Additional studies may be initiated by the company
(Postmarketing studies sometimes call “Phase IV”)
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Compound Success Rates by Stages
Compound Success
Rates by Stage
Discovery
(2-10 Years)
Preclinical Testing
5,000-10,000
screened
Laboratory and animal testing
Phase I
20-80 healthy volunteers used to
determine safety and dosage
250
enter preclinical testing
Phase II
100-300 patient volunteers used
to look for efficacy and side effects
5
enter clinical testing
Phase III
1,000-5,000 patient volunteers used to monitor
adverse reactions to long-term use
FDA Review/
Approval
1
approved by the FDA
Additional
Postmarketing Testing
0
4
8
12
16
Years
Source: PhRMA, based on data from Center for the Study of Drug Development, Tufts University, 1995.
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SCIENTIFIC EXCELLENCE
• Study Design
• Choice of Investigator
• Execution (Monitoring)
• Data Collection and Analysis
• Freedom from:
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Bias
Sloppiness
Unexpected Events
Fraud
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BIAS IN CLINICAL TRIALS
• The Investigator
• The Nurse
• The Technician
• The Patient
• The Patient’s Relatives
• The Drug Company
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STANDARD METHODS
OF
BIAS CONTROL
• Protocol (Plan)
• Randomization
• Blinding
• Placebo
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SURVEILLANCE OF
CLINICAL TRIAL PREFORMANCE
• Record Keeping and Data Integrity
• Time and Resources for Investigator and Staff
• Auditing Financial Records
• Patient Accrual Rate Monitoring
• Performance Milestones
• Protocol Adherence
• Regulatory Compliance
• Sponsor Communications
• Sponsor Satisfaction Assessment
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THE CHAIN OF TRUTH IN DRUG
DISCOVERY AND DEVELOPMENT
• Molecular Development
•
•
•
•
•
•
•
•
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
Synthesis Scale-Up

Basic Pharmacology

Early Toxicology

Pharmaceutical Development

Phase I in Humans

Phase II in Humans

Phase III in Humans

Registration
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STOP!
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Backup Slides
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MARKET RESEARCH:
• Not Inherently Innovative
• Needs to Follow an Innovative
Scientific Idea (These Ideas Come
From Basic & Clinical Investigators)
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Companies Are Desperate to
Obtain Critical Information As
Rapidly as Possible on Each
Product. For Products of High
Market Value, the Pace Is Often
Frenzied
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INDUSTRY NEEDS
ACADEMIA FOR:
Consultations on Large Decisions
Access to Critical Masses of Patient
Populations
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CRITICAL ELEMENTS IN ACADEMICINDUSTRY COLLABORATION
1) The Contract Research Element
2) The Consultantship Element
3) The Employee Element
4) The Technology Transfer Element
5) The Gift Element
(Waugaman & Porter, 1992)
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POTENTIAL BENEFITS FOR
ACADEMIC HEALTH CENTERS
•
•
•
•
•
Additional Clinical Trial Opportunities, Revenues
Access to Latest Drug and Device Technology
Increased Visibility in Publications
Increased Patient Numbers
Retention of Clinical Faculty Researchers
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ACADEMIC COLLABORATION WITH INDUSTRY
-THE UPSIDE
1) Provides Source of Income
2) Provides Source of Publications
3) Applied Science  Fruits for
Patients Are In The Near Term
4) Basic Science Discoveries May Be
Exploited More Rapidly
(Waugaman & Porter, 1992)
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ACADEMIC COLLABORATION WITH INDUSTRY
- THE DOWNSIDE
1) Income Is Often Unpredictable/Unstable
2) Publications Can Be Reviewed/Delayed
3) Peer Recognition Marginal
4) Few Basic Science Opportunities For
Collaboration
5) Fear Of Publication May Preclude Academia
(Waugaman & Porter, 1992)
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PROBLEM WITH INDUSTRY/ACADEMIC
RELATIONSHIPS
1) Benefits Are Not Uniformly
Spread Through Academia
2) Companies Are Not Uniform In
Their Dealings
- Company to Company
- Project to Project
3) Business Leaders Are Impatient
With Universities’ Needs and
Points of View
4) All This Made More Difficult By
- Changes In Tax Law
- Corporate Restructuring
- Difficult Market Conditions
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(Waugaman
& Porter, 1992)
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Industry needs from Academic Medical Centers:
a) Patents
b) Prestige
c) Patients
d) Publications
e) Personnel
f) Profit
“These elements will be even more important as
cost-containment measures impinge on the
revenue stream, and as technological
sophistication and increasing regulatory
requirements drive up the cost of the drug
development.”
(Cooper & Novitch, 1992)
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Many…“ISTs”
Involved
in
Pharma R&D
From D. Tobias, Wyeth Research
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Many…“ISTs” Involved in Pharma
R&D
Chemists
• Organic
• Physical
• Analytical
• Combinatorial
• Synthesis
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Many…“ISTs” Involved in Pharma
R&D
Chemists
• Organic
• Physical
• Analytical
• Combinatorial
• Synthesis
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Biologists
• Pharmacologists
• Cellular
• Molecular
• Bacteriologists
• Virologists
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Many…“ISTs” Involved in Pharma
R&D
Chemists
• Organic
• Physical
• Analytical
• Combinatorial
• Synthesis
Biologists
• Pharmacologists
• Cellular
• Molecular
• Bacteriologists
• Virologists
Pharmacists
• Formulations
• Clinical Supply
• Product Stability
• Analytical
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Many…“ISTs” Involved in Pharma
R&D
Chemists
• Organic
• Physical
• Analytical
• Combinatorial
• Synthesis
•
•
•
•
•
Clinical Specialists
Medical Monitors
Clinical Scientists
Medical Writers
Biostatisticians
Data Management
Specialists
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Biologists
• Pharmacologists
• Cellular
• Molecular
• Bacteriologists
• Virologists
Pharmacists
• Formulations
• Clinical Supply
• Product Stability
• Analytical
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Many…“ISTs” Involved in Pharma
R&D
Chemists
• Organic
• Physical
• Analytical
• Combinatorial
• Synthesis
•
•
•
•
•
Clinical Specialists
Medical Monitors
Clinical Scientists
Medical Writers
Biostatisticians
Data Management
Specialists
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Biologists
• Pharmacologists
• Cellular
• Molecular
• Bacteriologists
• Virologists
Pharmacists
• Formulations
• Clinical Supply
• Product Stability
• Analytical
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Specialists
• Toxicologists
• Drug Metabolism
• Project Managers
• Human Relations
• Regulatory
• Legal
• Safety Surveillance
• Communications
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Discovery
Screening
Specific Tests to
Aid in Selection
(e.g. Bioassay or
in vitro
Functionality)
Investigate Side-Effect
Issues and Other
Therapeutic
Indications
Phase IV
Monitoring
General Pharmacology
Profiles and Special
Models
GENERAL
PHARMACOLOGY
IND
Mechanistic Follow-up
Studies and Other
Therapeutic Indications
Investigate SideEffect Issues
NDA
Candidate
Nomination for
Development
Investigate SideEffect Issues and
Other Therapeutic
Indications
Clinical
Trials
(Figure 1. Flow Diagram Illustrating Where General Pharmacology Studies Can Impact
During the Typical Drug Discovery and Development Process. IND, Investigational New
Drug; NDA, New Drug Application
(From Fossa and Bucholtz, 1994)
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BACK-UP SLIDES
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Chronology of Drug Innovation
Cell pharmacology/
Molecular biology
Sources/Innovations
genetic
engineering
enzymes
receptors
serendipity
Chronic
Degenerative
Disease
Associated
with aging,
Inflammation,
cancer
Biotech
drugs
Lipid lowerers,
ACE-inhibitors
H2-antagonists
Beta blockers
Natural products
And derivatives
NSAIDs
psychotropics
Penicillins
Sulphanamides
aspirin
New Therapeutic Cycles
1900
1950
1960
1970
1980
1990
2000
2010
2020
2030
Source: Lehman Brothers Pharmaceutical Research
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THE DYNAMISM OF
COMPANY PRIORITIES:
Shifting of Company Priorities - Up or Down - Can
Occur Because of Internal News on an Existing
Product in the Pipeline of From Competitive
Intelligence that Boosts or Damages Such a Produce.
Rapidly Conducted Investigations of High Quality,
Coupled the Continuous Flow of Information About
Each Compound as Its Eventual Likelihood of
Success Are the Drivers of the Business; It Is Not
Simply a Quest for New Knowledge for Its Own Sake
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The Role of the Champion in
Drug Development
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