This book systematically explains how LCM strategies can help the pharmaceutical industry maximize the value of its patented brands through effective drug development programs and brand management. The authors share their combined 50 years of experience in the industry, citing numerous recent examples and case histories, and demonstrating how different measures can be combined to create winning strategies. The text helps pharmaceutical professionals understand challenges facing the industry and the role LCM has in confronting them, and offers a look ahead to predict which LCM strategies will continue to be effective in the future. A must-read for pharmaceutical executives and managers.
Inhaltsverzeichnis
Acknowledgments xvii
Introduction xix
Part A Lifecycle Management Business Environment 1
1. Challenges Facing the Branded Drug Industry 3
1. 1 Depleted NME Pipelines/Lower R&D Efficiency 4
1. 2 Higher Development Costs 8
1. 3 Safety Concerns 9
1. 4 Tougher Environment for Pricing, Reimbursement, and Listing 12
1. 5 Increased Competition 16
1. 6 Earlier Genericization 17
1. 7 Faster Sales Erosion Following Patent Expiry 18
1. 8 Poor Image of Branded Drug Industry 20
1. 8. 1 Prosperity of the Branded Drug Industry 21
1. 8. 2 Lack of Innovation 22
1. 8. 3 Marketing Spend and Tactics 22
1. 8. 4 Safety Issues 23
1. 8. 5 Keeping Generics Off the Market 24
1. 9 Diversification 26
2. The Life Cycle of Industries, Technologies, and Brands 30
2. 1 Diffusion of Innovations 30
2. 2 The Lifecycle Curve 32
2. 3 Lifecycle Phases 34
2. 3. 1 Development Phase 34
2. 3. 2 Introduction Phase 35
2. 3. 3 Growth Phase 35
2. 3. 4 Maturity Phase 36
2. 3. 5 Decline Phase 36
3. The Life Cycle of a Pharmaceutical Brand 38
3. 1 Lifecycle Curve of Pharmaceuticals 41
3. 1. 1 Slow Rate of Growth during the Growth Phase 42
3. 1. 2 Lack of a True Maturity Phase 43
3. 1. 3 Precipitous Decline Phase 43
3. 2 Factors Affecting Rate of Conversion to Generics 44
3. 2. 1 Government Policy 44
3. 2. 2 Disease 44
3. 2. 3 Size of Brand 45
3. 2. 4 Hospital versus Nonhospital Drug Usage 45
3. 2. 5 Active Substance and Other Barriers to Entry 46
3. 3 The Life Cycle of a Pharmaceutical Brand 46
Part B Lifecycle Management Regulatory and Legal Environment 55
4. The Generic Approval Process 57
4. 1 United States 57
4. 2 Europe 59
4. 3 Japan 61
5. Hatch-Waxman Legislation and Its Effects on LCM 62
5. 1 Hatch-Waxman Act of 1984 62
5. 2 Medicare Modernization Act of 2003 64
5. 3 FDA Amendments Act of 2007 65
5. 4 Q1 Program Supplemental Funding Act of 2008 66
5. 5 Discussion of Hatch-Waxman Legislation 66
6. U. S. Health-Care Reform 2010 69
7. European Sector Inquiry 72
Part C Patents and Exclusivities 77
8. Patents and Other Intellectual Property Rights 79
8. 1 Nonpatent Intellectual Property Rights 79
8. 2 What Are Patents? 81
8. 3 What Is Patentable? 83
8. 3. 1 Patentable Subject Matter 83
8. 3. 2 Novelty 84
8. 3. 3 Inventive Step 85
8. 3. 4 Utility 86
8. 3. 5 Disclosure 86
8. 4 How Long Does a Patent Last? 87
8. 5 Patent Term Restoration in the United States 87
8. 6 Supplementary Protection Certificates in Europe 88
8. 7 Patent Term Extension in Japan 89
8. 8 How Are Patents Obtained? 89
8. 9 Patent Enforcement 91
8. 10 Types of Patents 92
8. 10. 1 Composition of Matter Patent 93
8. 10. 2 Medical Use Patent 93
8. 10. 3 Formulation Patent 94
8. 11 KSR versus Teleflex-Raising the Nonobviousness Bar 94
8. 12 Patent Strategy 96
9. Nonpatent Exclusivities 99
9. 1 NCE Exclusivity (United States) 99
9. 2 New Clinical Study Exclusivity (United States) 100
9. 3 Data and Marketing Exclusivity (Europe) 100
9. 4 Data Exclusivity (Japan) 101
9. 5 Orphan Drug Exclusivity 101
9. 6 Pediatric Exclusivity 103
9. 7 180-Day Generic Product Exclusivity 105
10. Patent Settlements 107
Part D Developmental LCM 113
11. Strategic Principles of Developmental LCM 115
11. 1 Developmental LCM Goal 1: Provide a Meaningful Improvement in Clinical Profile 116
11. 2 Developmental LCM Goal 2: Increase the Potential Real-World Patient Potential for the Brand 118
11. 3 Developmental LCM Goal 3: The Ability to Generate an ROI 120
11. 4 Developmental LCM Goal 4: The Ability to Enhance Market Exclusivity of the Brand Franchise 121
12. Indication Expansion and Sequencing 123
12. 1 Categories of Indication Expansion 123
13. Patient Subpopulations and Personalized Medicine 131
13. 1 What Does a Good Patient Selection Strategy Look Like? 135
13. 2 Patient Selection without Predictive Criteria: Post Hoc Approaches 138
13. 3 What about the Patients Who Are Not Selected? 139
14. New Dosage Strengths, New Dosage Regimens 140
14. 1 New Dosage Strengths 140
14. 2 New Dosage Regimens 141
15. Reformulation, New Routes of Administration, and Drug Delivery 143
15. 1 Reformulation and New Routes of Administration 143
15. 1. 1 Switch and Grow Strategy 143
15. 1. 2 Expand and Grow Strategy 145
15. 1. 3 Generic Defense 145
15. 2 Drug Delivery Devices 149
16. Fixed-Dose Combinations (FDCs) and Co-Packaging 152
17. Second-Generation Products and Modified Chemistry 159
17. 1 Isomerism 160
17. 2 Polymorphism 161
17. 3 Salts, Ethers, and Esters 162
17. 4 Prodrugs and Metabolites 163
18. Other Developmental LCM Strategies 165
18. 1 Manufacturing Strategies 165
18. 2 White Papers and Citizen Petitions 166
Part E Commercial LCM 167
19. Strategic Principles of Commercial LCM 169
19. 1 Commercial LCM Goal 1: The Ability to Drive Widespread and Preferential Patient Access to the Brand 170
19. 2 Commercial LCM Goal 2: The Ability to Defend Market Access and Formulary Position 170
19. 3 Commercial LCM Goal 3: The Ability to Optimize Profi tability of the Brand Franchise 171
20. Geographical Expansion and Optimization 172
20. 1 Geographic Expansion 174
20. 2 Harmonization and Rationalization 175
21. OTC Switching 178
21. 1 What to Switch: Choosing the Best Approach 179
21. 2 Where to Switch: Dealing with Intermarket Variability 181
21. 3 When to Switch: Balancing the Product Life Cycle? 183
21. 4 How to Make the Switch Successful: What Corporate Support Is Required? 184
22. Brand Loyalty and Service Programs 186
23. Strategic Pricing Strategies 190
23. 1 Pricing Strategy and Tactics in the Launch and Growth Phases 190
23. 2 Pricing Strategy and Tactics Following Patent Expiry 193
24. Generic Strategies and Tactics 198
Building a Generic Portfolio: Old versus New Thinking 202
25. Exit Strategies 204
Executing the Exit Strategy 206
Part F Biologics and Biosimilars 207
26. Biologics and LCM 209
26. 1 Emergence of Biotech 209
26. 2 Some Definitions 210
26. 2. 1 Biologics 210
26. 3 Uptake and Value of Biologics 211
26. 4 LCM of Biologics 213
26. 4. 1 Next-Generation Biologics 213
26. 4. 2 Reformulation 214
26. 4. 3 Indication Expansion 215
26. 4. 4 Self-Injection Devices 215
27. Biosimilars and Their Impact on Biologic LCM 217
27. 1 Changing Terminology: Biogenerics, Biosimilars, and FOBs 217
27. 2 Why Are Biosimilars a Big Deal? 219
27. 3 How Are Biosimilars Different? 220
27. 4 Biosimilar Approval Pathways 220
27. 4. 1 Biosimilars in Europe 220
27. 4. 2 Biosimilars in the United States 221
27. 4. 3 Biosimilars around the World 222
27. 5 Substitution of Biosimilars 223
27. 5. 1 Automatic Substitution 223
27. 5. 2 Therapeutic Substitution 224
27. 6 Innovator Responses to Biosimilar Threats 225
27. 7 The Future for Biologics LCM 226
27. 7. 1 Legal Strategies in the United States 227
27. 7. 2 Indication Expansion in Europe 228
27. 7. 3 Brand Loyalty Programs and Services 229
27. 8 The Emergence of the "Innovasimilar" Biopharma Company 229
27. 9 Final Words 231
Part G The Integrated Brand LCM Strategy And its Implementation 233
28. Strategic Goals of LCM Brand Plans 235
28. 1 Position to Market 235
28. 2 Comparative Clinical Profile versus Gold Standard 237
28. 3 Level of Market Unmet Need 237
29. Ten Keys to Successful LCM 238
29. 1 Excellent Functional Expertise 238
29. 1. 1 Patent Attorneys 239
29. 1. 2 Regulatory Affairs 240
29. 1. 3 Clinical Development 240
29. 1. 4 Formulation Scientists 241
29. 1. 5 Marketing and Sales 242
29. 1. 6 Manufacturing 243
29. 2 Visible Management Support 244
29. 3 Unambiguous Ownership 245
29. 4 An Early Start 246
29. 5 A Robust "Broad to Bespoke" Process 248
29. 6 Focus on "High LCM Value Brands" 249
29. 7 Adequate Resources 250
29. 8 Measurements and Rewards 250
29. 9 Training and Support 252
29. 10 Realism 252
30. Organizational Structures and Systems for Ensuring Successful LCM 254
30. 1 Organization of Project and Brand Management 254
30. 1. 1 Functional Structure 255
30. 1. 2 Project Structure 255
30. 1. 3 Matrix Structure 257
30. 2 Project and Brand LCM Structures 259
30. 3 LCM Center of Excellence 263
30. 4 Composition of the LCM CoE 266
31. The LCM Process: Description, Timing, and Participants 268
31. 1 Purpose of the LCM Process 268
31. 2 Timing of the LCM Process 269
31. 3 Description of the LCM Process 271
Part H Integrating LCM with Portfolio Management 277
32. Principles of Portfolio Management 279
33. LCM Projects in the Development Portfolio 284
34. Managing Established Brand Portfolios 286
34. 1 What Do You Do with a Priority Established Brand? 288
34. 2 What about the Nonpriority Brands? 289
34. 3 Building the Ideal Established Brands Portfolio 290
Conclusions 291
Appendix: Case histories 294
A. 1 Market and Product-Shaping Dynamics in Action 294
Alzheimer's Disease Therapies: Aricept® , Exelon® , and Reminyl® /Razadyne® 294
Learnings 297
A. 2 Optimizing Clinical Profi le versus Gold Standards 298
Angiotensin II Receptor Blockers (ARBs): Cozaar® , Micardis® , and Benicar® 298
Learnings 299
A. 3 Partnering to Ensure Reimbursement and Collection of Cost-Effectiveness Data 299
Aricept 299
Learnings 301
A. 4 Active Metabolites and Late-Listed Patents 301
Buspar® 301
Learnings 303
A. 5 A Fixed-Dose Combination (FDC) That Could Not Fail, or Could It? 303
Caduet® 303
Learnings 304
A. 6 Indication Expansion 305
Certican® /Zortress® and Afi nitor® 305
Learnings 306
A. 7 Killing a Franchise through Over-the-Counter (OTC) Switching 307
Claritin® 307
Learnings 308
A. 8 Moving FDCs to the Fore in Diabetes 308
Diabetes Therapies: Glucophage® , Avandia® , Actos® , and Januvia® 308
Learnings 310
A. 9 FDCs and Multiple Dosage Strengths 310
Diovan® and Tekturna® /Rasilez® 310
Learnings 312
A. 10 Building a Compliance Support Program 312
Enbrel® 312
Learnings 314
A. 11 Targeting Responders with High-Price Cancer Agents 314
Erbitux® 314
Learnings 315
A. 12 Failure of a "No-Brainer" LCM Strategy 315
Exubera® 315
Learnings 319
A. 13 At-Risk Launches and Prodrug Patents 320
Famvir® 320
Learnings 321
A. 14 New Dosages, FDC, and Patent Litigation 322
Fosamax® 322
Learnings 324
A. 15 High Regulatory Hurdles for Lifestyle Drugs 325
Girosa® 325
Learnings 327
A. 16 Big Money from Orphan Indications 327
Gleevec® 327
Learnings 329
A. 17 Not Giving Up on a Controversial Brand 330
Iressa® 330
Learnings 332
A. 18 Expanding a Medical Aesthetics Franchise with an Ophthalmic Drug 332
Latisse® 332
Learnings 334
A. 19 Patent Expiry of the Biggest Drug Brand Ever 335
Lipitor® 335
Learnings 336
A. 20 Early Out-Licensing by Biotech: Take the Money and Run 336
Macugen® 336
Learnings 338
A. 21 Codevelopment and Comarketing Deals End in a Megamerger 338
Merck and Schering-Plough: Zetia® /Vytorin® and Claritin/Singulair® 338
Zetia/Vytorin 339
Claritin/Singulair 342
Learnings 343
A. 22 A Hugely Successful LLCM Switch Strategy: Business Needs and Reputational Issues Collide 344
Prilosec® and Nexium 344
The Facts 344
The Public Reaction 345
Learnings 347
A. 23 Combining Production Outsourcing with Settlement with a Generic Competitor 349
Nexium 349
Learnings 351
A. 24 Reformulating for Success in Osteoporosis 351
Osteoporosis Drugs: Fosamax, Actonel® , Boniva® , and Aclasta® 351
Learnings 353
A. 25 Isomerism, Polymorphism, and Settlements 354
Plavix® 354
Learnings 355
A. 26 Payers versus Brand for Patient Selection 356
Plavix and Brilinta 356
Learnings 357
A. 27 Litigation Can Delay Generic Entry in the OTC Field Too 358
Prilosec OTC 358
Learnings 359
A. 28 Inconsistent Court Decisions Can Hurt Both Brandand Generic Companies 360
Protonix® 360
Learnings 361
A. 29 Holding on to an Antipsychotic Franchise 362
Risperdal® /Invega® 362
Learnings 363
A. 30 LCM Creates an Almost Immortal Brand 364
Voltaren® 364
Learnings 365
A. 31 LCM of a Women's Health Franchise 366
The Yasmin® Family 366
Learnings 368
A. 32 Indication Expansion/New Dosage Strength 369
Zometa/Reclast® (Aclasta) 369
Learnings 370
Index 371
