Drug Discovery

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ISBN: 9780123695338 | 0123695333
Cover: Paperback
Copyright: 12/15/2005

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Everyone expects something from the drug industry. Physicians and patients, investors, regulators and administrators all have an active interest. Everyone wants to know what makes drugs work medically and economically. Why are drugs so expensive? Is it the drug companies or investors who demand high profits? What governs the pharmacoeconomics? Why are so few diseases treatable? This book opens the windows and doors of the industry telling the story of drug development by using real stories from inside the process.

PREFACE

xiii

ACKNOWLEDGMENTS

xix

ABOUT THE AUTHORS

xxi

INTRODUCTION: DELIVERING ON THE PROMISE

xxiii

PART I MEDICINES FOR SOCIETY

(76)

1. THE ART OF PUTTING A MOLECULE INTO MAN

(10)

The Pharmaceutical Industry: Perceptions and Misperceptions, Profits and Losses

(1)

A Strong, Regulated Dose of Safety

(2)

Companies' Failed Drugs Have Lots of Company

(1)

Patented Drugs vs. Generic Drugs: On the Table and Over the Counter

(2)

Who Does What in the Industry?

(4)

2. RAISING AND RISING EXPECTATIONS

(10)

What Society Needs from Pharma

(4)

What Pharma Needs from Society

(6)

3. HISTORY IS GOOD TO KNOW

(12)

Classical Drug Discovery

(2)

Glorious Serendipity

(2)

The Goodness of Side Effects

(1)

The Drug's Fate Becomes the Drug

(1)

Pathophysiology Reveals Drug Targets

(1)

Virtues and Problems of the Classical Pharmacology Paradigm in Drug Discovery

(1)

Merger Frenzy

(4)

4. THE BETTER BETA-BLOCKER BARRIER

(14)

The Largest Selling Beta-Blocker Now Costs 15 Cts/Day

(2)

Ironing out the Wrinkles of Botulinum Toxin

(1)

Painful Processes

(1)

Very Painful Processes

(1)

Exclusivity Isn't What It Used to Be

(2)

Unhealthy Competition

(2)

Some Diseases Just Cannot Be Treated Today

(1)

Safe Drugs Are Tried for Many Underserved Indications

(2)

Estimated Value of Medicine for Society

(2)

5. WHY SOME GOOD DRUGS Do NOT GET A CHANCE AND WHY OTHERS FAIL

(6)

Many Causes, Too Many Reasons

(2)

Patients Do Not Take the Drugs during the Trial

(1)

Patients Are Taking Other or Alternative Medicines

(2)

Diagnosis before Treatment

(1)

6. ABOUT THE ECONOMICS OF TARGET AND CLINICAL CANDIDATE SELECTION

(6)

Pharmacoeconomics 101: Some Underappreciated Truths

(1)

Why Do Drugs Fail after Phase I?

(1)

Official Causes for Attrition

(2)

Reasons for Stopping Clinical Development and the Fallout from Failure

(2)

7. TARGET-BASED DRUG DISCOVERY: PART I

(6)

Improving Therapeutic Ratios

(2)

The Relative Ease of Biologicals to Become Approved Drugs

(1)

Better to Let the Market Decide?

(3)

8. CHANGES NEED TO BE MADE

(10)

Points for Discussion

(1)

The Efficiency of the Drug Discovery Process Is Low

(1)

Major Drivers of Drug Discovery up to 1980

(2)

Major Drivers of Drug Discovery 2000

(2)

Bringing Attitudes in Line with Needs

(1)

Bringing the FDA in Line with Needs

(3)

Bringing Legislation in Line with Needs

(1)

PART II FROM BASICS TO BEDSIDE

(104)

9. TARGET-BASED DRUG DISCOVERY: PART II

(12)

The Emerging Divergence of Academia and Industry

(3)

Academia—Pharma Industry Discussions Are Sometimes Difficult

(1)

Target-Based Drug Discovery or Finding Clinical Candidates in an Academic Setting and What to Do When You've Found One

(4)

Adjusting Academic Truths to Industry Values or Putting the "I" in Industry

(4)

10. "DRUGABLE" TARGETS

(12)

Genomics and Drug Discovery for Patients

(1)

Genomics and "Drugable" Targets

(6)

Target Classes

(1)

Learning the Biology in Inflammation Leads to a Wealth of Targets

(2)

Cautionary Tales about Targets

100

(3)

11. SO MANY DRUGS, SO FEW ENTITIES

103

(8)

All about Structure

103

(4)

Blockbusters

107

(1)

Making Sense of the Chemistry

108

(3)

12. How TO FIND A CANDIDATE DRUG

111

(20)

Selecting Clinical Candidates for Trial

111

(1)

The Ideal Clinical Candidate According to the Company

112

(5)

The Proof of Principle Principle

117

(3)

Picking the Right Thing to Measure in a Trial: Surrogate Endpoints or Markers

120

(2)

Finding Clinical Candidates in Your Portfolio

122

(2)

Targets for the Optimists

124

(1)

Following Old Comfortable Formulas

125

(2)

Targets from Clinically Broadly Active—or Dirty—Drugs

127

(4)

13. PRACTICALITIES: THE HOOPS AND HURDLES OF BIG PHARMA

131

(10)

Why Is the Selection of a Clinical Candidate Such a Problem?

131

(1)

The Pipeline

132

(1)

Marketing Machinery

133

(1)

Navigating through the Clinical Candidate Selection Board at Big Pharma

134

(2)

Indirect Treatments and Surrogate Markers

136

(2)

Three Most Important Things: U.S. Market, U.S. Market, and U.S. Market

138

(1)

The Ideal Backup Compound

139

(1)

Why Are Clinical Candidates Being Selected at All?

140

(1)

14. PRACTICAL TRIALS FOR A BALANCED PORTFOLIO

141

(4)

Is Your Clinical Candidate Significantly Better?

141

(4)

15. HOW TO IMPROVE THE ODDS OF FINDING A SAFE DRUG THAT WORKS

145

(10)

Therapeutic Windows

145

(1)

Statistics of Failure

146

(2)

Ways of Playing It Safe

148

(7)

16. THE TRIBULATIONS OF CLINICAL TRIALS

155

(6)

What We Should Learn from Failed Trials

155

(1)

Agree in Advance with the FDA as to What Constitutes Success

156

(1)

Trials of Disease Progression

156

(2)

Marketing Moguls

158

(1)

Standing Alone against Placebo

159

(2)

17. LINKING PUTATIVE TARGETS TO DISEASE STATES

161

(10)

Clever Ways to Phenotype Including Self-Reported Phenotyping

161

(3)

Genomics- to Proteomics-Derived Putative Targets

164

(5)

From Transcriptional Profile to Drug in Four Years—Jules Verne and the Therapeutic Antibodies

169

(1)

Biologicals Are the "Low Hanging Fruit" of Genomics-Based Target Discovery

169

(2)

18. MORE WAYS TO LOOK FOR TARGETS

171

(10)

Reverse Pharmacology

171

(2)

Making the Most of Side Effects

173

(1)

A Lesson in Molecular Pharmacology: Making a Bandwagon

174

(2)

G-Protein Coupled Receptors

176

(2)

Orphan Receptors: Matching Drugs to Targets without Knowing Normal Function

178

(2)

Future Targets

180

(1)

PART III THE BUSINESS OF MAKING AND SELLING LEGAL DRUGS

181

(74)

19. THE BUSINESS BASICS (GENERAL)

183

(10)

Industry Attributes

183

(4)

Big Pharma Strengths

187

(2)

Balanced Portfolio of Clinical Candidates

189

(1)

Why So Many Biotechs?

190

(1)

Alliances, Cooperations, and Partnerships

191

(1)

Other Players

192

(1)

20. ADDING VALUE IN A GROWTH INDUSTRY

193

(16)

R&D of $26.4 Billion Produced Nine Drugs

193

(1)

Patents

194

(1)

Price Insensitivity and Other Business Drivers

195

(6)

Foreseen and Unforeseen Costs

201

(4)

Landscape Perturbations

205

(1)

Why Unmet Medical Needs Remain Unmet

206

(3)

21. WHAT'S THE MOST PROFITABLE APPROACH?

209

(8)

Chemical Innovation

209

(1)

Efficacious in Adversity

210

(2)

The Cost of Doing Pharma Research

212

(1)

The Price of Success

213

(1)

Success May Be Short Lived

214

(1)

The Cost of Failure

214

(3)

22. PHARMACOECONOMICS FOR BIOTECH

217

(10)

Dilemmas: Insurmountable Obstacles or Unachievable Goals of Own Drug Development, and the Dream and Reality of IPO

217

(1)

Share Risk: Partner with Big Pharma

218

(1)

Irrefutable Statistics: Not Every Drug for an Indication Will Make It

219

(3)

Science Fiction to Fact

222

(1)

Target Feast and Famine

222

(2)

The Scientific Basis of Drug Discovery Is Expanding

224

(1)

Are Biotechs Smarter?

225

(2)

23. SHRINKING VALUE OF TARGETS

227

(4)

Inflating Valuations

227

(3)

New Business of Wiser Biotechs

230

(1)

24. ASSESSING COMPANY ASSETS? LOOK IN THE LIBRARY

231

(6)

High-Throughput-Screening-Based Drug Discovery Process at Big Pharma

231

(2)

Hits against Receptors

233

(1)

Which Target Should Attract Investment?

234

(3)

25. TO MERGE OR NOT TO MERGE?

237

(6)

What Drives Mergers (Part 1)?

237

(5)

What Drives Mergers (Part 2)?

242

(1)

26. WORKING WITH THE FOOD AND DRUG ADMINISTRATION (FDA)

243

(8)

Embracing the FDA

243

(1)

What the FDA Does

244

(7)

27. REGULATING REGULATORY REGIMENS RELIABLY

251

(4)

Balancing Safety vs. Efficacy

251

(2)

Is There Something Wrong with the Patent Law?

253

(2)

PART IV WHAT WILL MATTER IN MAKING MEDICINES?

255

(40)

28. THE HYPOTHESIS IS: THERE IS A BETTER WAY

257

(10)

Proceed with Caution, but Proceed

257

(1)

Drug Development Remains Part Science and Part Art

258

(1)

Why Are We Missing So Many Targets and Treating So Few Diseases?

259

(3)

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Drug Discovery

Summary

Table of Contents

Supplemental Materials

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