Pharmaceutical Lifecycle Management – Making the Most of Each and Every Brand

<p>Acknowledgments xvii</p>
<p>Introduction xix</p>
<p>PART A Lifecycle Management Business Environment 1</p>
<p>1. Challenges Facing the Branded Drug Industry 3</p>
<p>1.1 Depleted NME Pipelines/Lower R&amp;D Efficiency 4</p>
<p>1.2 Higher Development Costs 8</p>
<p>1.3 Safety Concerns 9</p>
<p>1.4 Tougher Environment for Pricing, Reimbursement, and Listing 12</p>
<p>1.5 Increased Competition 16</p>
<p>1.6 Earlier Genericization 17</p>
<p>1.7 Faster Sales Erosion Following Patent Expiry 18</p>
<p>1.8 Poor Image of Branded Drug Industry 20</p>
<p>1.9 Diversification 26</p>
<p>2. The Life Cycle of Industries, Technologies, and Brands 30</p>
<p>2.1 Diffusion of Innovations 30</p>
<p>2.2 The Lifecycle Curve 32</p>
<p>2.3 Lifecycle Phases 34</p>
<p>3. The Life Cycle of a Pharmaceutical Brand 38</p>
<p>3.1 Lifecycle Curve of Pharmaceuticals 41</p>
<p>3.2 Factors Affecting Rate of Conversion to Generics 44</p>
<p>3.3 The Life Cycle of a Pharmaceutical Brand 46</p>
<p>PART B Lifecycle Management Regulatory and Legal Environment 55</p>
<p>4. The Generic Approval Process 57</p>
<p>4.1 United States 57</p>
<p>4.2 Europe 59</p>
<p>4.3 Japan 61</p>
<p>5. Hatch Waxman Legislation and Its Effects on LCM 62</p>
<p>5.1 Hatch Waxman Act of 1984 62</p>
<p>5.2 Medicare Modernization Act of 2003 64</p>
<p>5.3 FDA Amendments Act of 2007 65</p>
<p>5.4 Q1 Program Supplemental Funding Act of 2008 66</p>
<p>5.5 Discussion of Hatch–Waxman Legislation 66</p>
<p>6. U.S. Health–Care Reform 2010 69</p>
<p>7. European Sector Inquiry 72</p>
<p>PART C Patents and Exclusivities 77</p>
<p>8. Patents and Other Intellectual Property Rights 79</p>
<p>8.1 Nonpatent Intellectual Property Rights 79</p>
<p>8.2 What Are Patents? 81</p>
<p>8.3 What Is Patentable? 83</p>
<p>8.4 How Long Does a Patent Last? 87</p>
<p>8.5 Patent Term Restoration in the United States 87</p>
<p>8.6 Supplementary Protection Certificates in Europe 88</p>
<p>8.7 Patent Term Extension in Japan 89</p>
<p>8.8 How Are Patents Obtained? 89</p>
<p>8.9 Patent Enforcement 91</p>
<p>8.10 Types of Patents 92</p>
<p>8.11 KSR versus Teleflex Raising the Nonobviousness Bar 94</p>
<p>8.12 Patent Strategy 96</p>
<p>9. Nonpatent Exclusivities 99</p>
<p>9.1 NCE Exclusivity (United States) 99</p>
<p>9.2 New Clinical Study Exclusivity (United States) 100</p>
<p>9.3 Data and Marketing Exclusivity (Europe) 100</p>
<p>9.4 Data Exclusivity (Japan) 101</p>
<p>9.5 Orphan Drug Exclusivity 101</p>
<p>9.6 Pediatric Exclusivity 103</p>
<p>9.7 180–Day Generic Product Exclusivity 105</p>
<p>10. Patent Settlements 107</p>
<p>PART D Developmental LCM 113</p>
<p>11. Strategic Principles of Developmental LCM 115</p>
<p>11.1 Developmental LCM Goal 1: Provide a Meaningful Improvement in Clinical Profile 116</p>
<p>11.2 Developmental LCM Goal 2: Increase the Potential Real–World Patient Potential for the Brand 118</p>
<p>11.3 Developmental LCM Goal 3: The Ability to Generate an ROI 120</p>
<p>11.4 Developmental LCM Goal 4: The Ability to Enhance Market Exclusivity of the Brand Franchise 121</p>
<p>12. Indication Expansion and Sequencing 123</p>
<p>12.1 Categories of Indication Expansion 123</p>
<p>13. Patient Subpopulations and Personalized Medicine 131</p>
<p>13.1 What Does a Good Patient Selection Strategy Look Like? 135</p>
<p>13.2 Patient Selection without Predictive Criteria: Post Hoc Approaches 138</p>
<p>13.3 What about the Patients Who Are Not Selected? 139</p>
<p>14. New Dosage Strengths, New Dosage Regimens 140</p>
<p>14.1 New Dosage Strengths 140</p>
<p>14.2 New Dosage Regimens 141</p>
<p>15. Reformulation, New Routes of Administration, and D rug Delivery 143</p>
<p>15.1 Reformulation and New Routes of Administration 143</p>
<p>15.2 Drug Delivery Devices 149</p>
<p>16. Fixed–Dose Combinations (FDCs) and C o–Packaging 152</p>
<p>17. Second–Generation Products and Modified Chemistry 159</p>
<p>17.1 Isomerism 160</p>
<p>17.2 Polymorphism 161</p>
<p>17.3 Salts, Ethers, and Esters 162</p>
<p>17.4 Prodrugs and Metabolites 163</p>
<p>18. Other Development LCM Strategies 165</p>
<p>18.1 Manufacturing Strategies 165</p>
<p>18.2 White Papers and Citizen Petitions 166</p>
<p>PART E Commercial LCM 167</p>
<p>19. Strategic Principles of Commercial LCM 169</p>
<p>19.1 Commercial LCM Goal 1: The Ability to Drive Widespread and Preferential Patient Access to the Brand 170</p>
<p>19.2 Commercial LCM Goal 2: The Ability to Defend Market Access and Formulary Position 170</p>
<p>19.3 Commercial LCM Goal 3: The Ability to Optimize Profitability of the Brand Franchise 171</p>
<p>20. Geographical Expansion and Optimization 172</p>
<p>20.1 Geographic Expansion 174</p>
<p>20.2 Harmonization and Rationalization 175</p>
<p>21. OTC S witching 178</p>
<p>21.1 What to Switch: Choosing the Best Approach 179</p>
<p>21.2 Where to Switch: Dealing with Intermarket Variability 181</p>
<p>21.3 When to Switch: Balancing the Product Life Cycle? 183</p>
<p>21.4 How to Make the Switch Successful: What Corporate Support Is Required? 184</p>
<p>22. Brand Loyalty and Service Programs 186</p>
<p>23. Strategic Pricing Strategies 190</p>
<p>23.1 Pricing Strategy and Tactics in the Launch and Growth Phases 190</p>
<p>23.2 Pricing Strategy and Tactics Following Patent Expiry 193</p>
<p>24. Generic Strategies and Tactics 198</p>
<p>25. Exit Strategies 204</p>
<p>PART F Biologics and Biosimilars 207</p>
<p>26. Biologics and LCM 209</p>
<p>26.1 Emergence of Biotech 209</p>
<p>26.2 Some Definitions 210</p>
<p>26.2.1 Biologics 210</p>
<p>26.3 Uptake and Value of Biologics 211</p>
<p>26.4 LCM of Biologics 213</p>
<p>27. Biosimilars and T heir Impact on Biologic LCM 217</p>
<p>27.1 Changing Terminology: Biogenerics, Biosimilars, and FOBs 217</p>
<p>27.2 Why Are Biosimilars a Big Deal? 219</p>
<p>27.3 How Are Biosimilars Different? 220</p>
<p>27.4 Biosimilar Approval Pathways 220</p>
<p>27.5 Substitution of Biosimilars 223</p>
<p>27.6 Innovator Responses to Biosimilar Threats 225</p>
<p>27.7 The Future for Biologics LCM 226</p>
<p>27.8 The Emergence of the "Innovasimilar" Biopharma Company 229</p>
<p>27.9 Final Words 231</p>
<p>PART G The Integrated Brand LCM Strategy and Its Implementation 233</p>
<p>28. Strategic Goals of LCM Brand Plans 235</p>
<p>28.1 Position to Market 235</p>
<p>28.2 Comparative Clinical Profile versus Gold Standard 237</p>
<p>28.3 Level of Market Unmet Need 237</p>
<p>29. Ten Keys to Successful LCM 238</p>
<p>29.1 Excellent Functional Expertise 238</p>
<p>29.2 Visible Management Support 244</p>
<p>29.3 Unambiguous Ownership 245</p>
<p>29.4 An Early Start 246</p>
<p>29.5 A Robust Broad to Bespoke Process 248</p>
<p>29.6 Focus on High LCM Value Brands 249</p>
<p>29.7 Adequate Resources 250</p>
<p>29.8 Measurements and Rewards 250</p>
<p>29.9 Training and Support 252</p>
<p>29.10 Realism 252</p>
<p>30. Organizational Structures and Systems for Ensuring Successful LCM 254</p>
<p>30.1 Organization of Project and Brand Management 254</p>
<p>30.2 Project and Brand LCM Structures 259</p>
<p>30.3 LCM Center of Excellence 263</p>
<p>30.4 Composition of the LCM CoE 266</p>
<p>31. The LCM Process: Description, Timing, and Participants 268</p>
<p>31.1 Purpose of the LCM Process 268</p>
<p>31.2 Timing of the LCM Process 269</p>
<p>31.3 Description of the LCM Process 271</p>
<p>PART H Integrating LCM with Portfolio Management 277</p>
<p>32. Principles of Portfolio Management 279</p>
<p>33. LCM Projects in the Development Portfolio 284</p>
<p>34. Managing Established Brand Portfolios 286</p>
<p>34.1 What Do You Do with a Priority Established Brand? 288</p>
<p>34.2 What about the Nonpriority Brands? 289</p>
<p>34.3 Building the Ideal Established Brands Portfolio 290</p>
<p>Conclusions 291</p>
<p>APPENDIX: Case Histories 294</p>
<p>1 Case History: Market and Product–Shaping Dynamics in Action 294</p>
<p>2 Case History: Optimizing Clinical Profile versus Gold Standards 298</p>
<p>3 Case History: Partnering to Ensure Reimbursement and Collect Cost–Effectiveness Data 299</p>
<p>4 Case History: Active Metabolites and Late–Listed Patents 301</p>
<p>5 Case History: A Fixed–Dose Combination (FDC) that Could Not Fail, or Could It? 303</p>
<p>6 Case History: Indication Expansion 305</p>
<p>7 Case History: Killing a Franchise through Over–the–Counter (OTC) Switching 307</p>
<p>8 Case History: Moving FDCs to the Fore in Diabetes 308</p>
<p>9 Case History: FDCs and Multiple Dosage Strengths 310</p>
<p>10 Case History: Building Compliance Support Program 312</p>
<p>11 Case History: Targeting Responders with High–Price Cancer Agents 314</p>
<p>12 Case History: Failure of a "No–Brainer" LCM Strategy 315</p>
<p>13 Case History: At–Risk Launches and Prodrug Patents 320</p>
<p>14 Case History: New Dosages, FDC, and Patent Litigation 322</p>
<p>15 Case History: High Regulatory Hurdles for Lifestyle Drugs 325</p>
<p>16 Case History: Big Money from Orphan Indications 327</p>
<p>17 Case History: Not Giving Up on a Controversial Brand 330</p>
<p>18 Case History: Expanding a Medical Aesthetics Franchise with an Ophthalmic Drug 332</p>
<p>19 Case History: Patent Expiry of the Biggest Drug Brand Ever 335</p>
<p>20 Case History: Early Out–Licensing by Biotech: Take the Money and Run 336</p>
<p>21 Case History: Codevelopment and Comarketing Deals End in a Megamerger 338</p>
<p>22 Case History: A Hugely Successful LLCM Switch Strategy: Business Needs and Reputational Issues Collide 344</p>
<p>23 Case History: Combining Production Outsourcing with Settlement with a Generic Competitor 349</p>
<p>24 Case History: Reformulating for Success in Osteoporosis 351</p>
<p>25 Case History: Isomerism, Polymorphism, and Settlements 354</p>
<p>26 Case History: Payers versus Brand for Patient Selection 356</p>
<p>27 Case History: Litigation Can Delay Generic Entry in the OTC Field Too 358</p>
<p>28 Case History: Inconsistent Court Decisions Can Hurt Both Brand and Generic Companies 360</p>
<p>29 Case History: Holding on to an Antipsychotic Franchise 362</p>
<p>30 Case History: LCM Creates an Almost Immortal Brand 364</p>
<p>31 Case History: LCM of a Women s Health Franchise 366</p>
<p>32 Case History: Indication Expansion/New Dosage Strength 369</p>
<p>INDEX 371</p>