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December 31st, 2009 admin No comments

Optimizing Lifecycle Management: Maximizing Commercial Lifespan Through Label Expansion And Combination Products

This report investigates three goals in optimizing product potential- expanding the drug's patent protected lifespan, accessing broader patient populations and launching line-extensions via fixed dose combinations. The key success factors in each of these pursuits have been clearly identified, emerging trends have been presented and the underlying concepts have been explained to provide a clear understanding of current industry dynamics. Case studies on popular products have been used to illustrate these concepts in the real world. An in-depth analysis of drug approval data provides context for the issues discussed. This information is juxtaposed with historic sales data to explore the correlation between the strategies employed and revenue potential.

This report explains the basics of drug lifecycle and investigates three goals in optimizing product potential- expanding the drug's patent protected lifespan, accessing broader patient populations and launching line-extensions via FDCs.

The key success factors in each of these pursuits have been clearly identified, emerging trends have been presented and the underlying concepts have been explained to give the reader a clear understanding of current industry dynamics. Case studies on popular products have been used to illustrate these concepts in the real world.

An in-depth analysis of drug approval data provides context for the issues discussed. This information is juxtaposed with historic sales data to explore the correlation between the strategies employed and revenue potential.

Key findings

Drug manufacturers must make the best strategic use of the patent-protected lifespan of a drug, or else risk losing the profit incentives they perceived at the start of the project. (Ch. 1)

In light of the increasing complexity of biopharmaceutical patenting, the ‘freedom to operate', i.e. to commercialize the invention, is coming under increasing scrutiny. (Ch. 2)

The US Congress' emerging stance on data exclusivity provisions for biologics will define the length of time a biotechnology company can keep out generic competition in new indications. The biotech industry's stance is that the current provisions do not provide for enough time to profit from their post-approval R&D investments. (Ch. 2)

The potential for post-approval label expansion is much greater for biologics in comparison to small molecule pharmaceutical drugs. Most biologics on the market today can expect to add significant revenue streams via new indications, and potentially extend their commercial lifespan. (Ch 3)

Over 45% of all new indication approvals granted by the FDA since 1998 belong to drugs that fall in the Genito-urinary system and Nervous system.

If an FDC is launched close to the loss of exclusivity date of the constituent brand, it may be interpreted as a marketing tactic to limit post-LoE revenue losses. If launched early, it may show intent to cater to a genuine unmet need, or to legitimately maximize the potential of the parent molecule(s). (Ch. 4)

Scope of the report

In-depth case studies explore the real-world execution of the issues and challenges discussed in the report.

Analysis of historic drug approval data provides the reader with contextual reference points.

Case studies on Vytorin, Advair and BiDil illustrate the strategies employed by three leading FDC brands.

Brand histories of Yaz, Remicade and Seroquel show how label expansion is fundamental to successful lifecycle management.

Where applicable, these strategies are discussed with reference to specific therapeutic areas or geographies.

Issues related to biologics are highlighted to indicate where they differ from small molecule drugs.

Use this report to

Gain an understanding of legal provision for patent protection and data exclusivity. Understand their role in the context of product lifecycle management

Utilize the historical data on NDA approvals to identify trends and build assumptions into competitive landscape forecasts.

Understand the stance of key stakeholders and implications of off-label drug usage.

Understand the role of FDCs in optimizing the commercial potential of a product asset, and the main challenges in their commercialization

Juxtapose historic sales performance with the timing of indication expansion and FDC based strategies to assess the success or failure

Table of Contents :

Optimizing Lifecycle Management
Executive summary 8
Product lifecycle and management challenges 8
Influencing the commercial lifespan of the drug 9
Accessing broader patient populations 10
Fixed dose combinations 11
Chapter 1 Product lifecycle and management challenges 14
Summary 14
Introduction 15
The lifecycle of biopharmaceutical drugs 15
Development lifecycle 17
Commercial lifecycle 22
Managing the lifecycle 22
Longer development time 23
Slower product uptake via reimbursement hurdles 24
Peak sales potential is reduced by higher competition 25
Earlier lifecycle decline due to therapeutic substitution 26
Chapter 2 Influencing the commercial lifespan of a drug 30
Summary 30
Bargaining power of biopharmaceutical brands 31
Brand equity 31
Patent protection and "freedom to operate" 32
Strategic patenting 33
Patent prosecution superhighway 35
Patent protection for biologics 35
Data exclusivity 36
Difference between data exclusivity and patent protection 40
8+2+1 system in the EU 40
Data exclusivity in the US 42
Data exclusivity in Japan 43
Data exclusivity in the context of biologics 44
Chapter 3 Accessing broader patient populations 46
Summary 46
Drug labeling and market access 47
Off-label drug usage 47
Commercial incentives and disincentives 48
Payors stance on off-label reimbursement 49
Case study: Avastin and Lucentis 51
Expanding the label 53
Role in product lifecycle management 53
New indications 53
Pediatric extensions and special populations 54
Modified indications and expanded usage 54
Case study: Yaz 55
Case study: Remicade 58
Indication expansion 59
Choosing the primary indication 61
Related versus unrelated indications 63
Sequence of indication expansion 64
Timing of indication expansion 65
Launching early in commercial lifecycle 68
Launching late in commercial lifecycle 69
Seroquel: Using indication expansion and drug reformulation synergistically 70
Recent trends in indication expansion 72
Indication expansion for NDAs 72
Indication expansion for biologics 75
Chapter 4 Fixed dose combinations 80
Summary 80
Introduction 81
Clinical challenges in FDC development 81
FDC patents 82
Data exclusivity for FDCs 83
Role in product lifecycle maximization 83
Case study: Advair's role in GSK's asthma franchise 85
Case study: How Vytorin influenced Zocor's patent expiry 88
Case study: BiDil's value proposition reinvented 90
FDC uptake by geography 91
Case study: FDCs for hypertension 91
Clinical rationale 93
Synergistic efficacy or safety 94
Easier Rx management 95
Correlation between FDC usage and drug compliance 95
Correlation between drug compliance & improved clinical outcomes 96
FDC usage by therapy area 96
Key success factors and competitive hurdles 98
Endorsement by treatment guidelines 98
Perceived synergy effects over free combination 99
Compliance advantage over the free combination 99
Usage of mono compounds prior to FDC launch 99
Discount compared to cheapest free combination 100
Time-to-LOE of parent brand 101
Chapter 5 Appendix 103
Primary research methodology 103
Glossary 107
Index 111
List of Figures
Figure 1.1: Summary of lifecycle of medicinal drugs 17
Figure 1.2: Transition probabilities for clinical phases 18
Figure 1.3: Out-of-pocket and capitalized costs of developing a drug ($m) 19
Figure 1.4: Time taken for development of new pharma & biotech drugs 20
Figure 1.5: Approval timelines at CDER for priority NDAs, 1999-08 21
Figure 1.6: Approval timelines at CDER for standard NDAs, 1999-08 21
Figure 1.7: Imperatives of efficient lifecycle management 23
Figure 1.8: Increasing importance of payors as stakeholders 24
Figure 1.9: Tougher payor environments are slowing product uptake 25
Figure 1.10: Therapeutic substitution and formulary access 27
Figure 2.11: 8+2+1 data exclusivity system in Europe 41
Figure 2.12: Data exclusivity and patent protection in the US 43
Figure 3.13: On and off-label decision making by payors 50
Figure 3.14: Off-label usage of Avastin: a pharmacoeconomic model for wet AMD 52
Figure 3.15: Yaz: Label expansion & sales growth - US ($m), 2006-08 57
Figure 3.16: Remicade: Label expansion & sales growth - US ($m), 2001-08 59
Figure 3.17: Time between launch of original and new indications in the US (by ATC), 1999-08 66
Figure 3.18: Time between launch of original and new indications in the US (by ATC), 1999-08 (contd) 67
Figure 3.19: Considerations in launching new indications early in the lifecycle 69
Figure 3.20: Considerations in launching new indications late in the lifecycle 70
Figure 3.21: Lifecycle management: Seroquel and Seroquel XR 71
Figure 3.22: New indication approvals for NDAs, 1999-2008 73
Figure 3.23: New indication approvals for Orphan drugs, 1999-08 73
Figure 3.24: New indication approvals with priority reviews, 1999-08 74
Figure 3.25: Increasing clinical and commercial potential for Remicade 77
Figure 4.26: FDC approvals in the US, 1999-08 84
Figure 4.27: Advair: FDA approvals and patent protection 86
Figure 4.28: Advair-Serevent sales in the US: maintaining revenues post patent expiry of Flovent 87
Figure 4.29: Zocor-Vytorin-Zetia brand timeline 88
Figure 4.30: Cushioning the patent cliff: Zocor-Vytorin-Zetia sales in US ($m), 2001-08 89
Figure 4.31: FDC usage for hypertension across major markets 93
Figure 4.32: Drug classes with maximum FDC approvals in the US, 1999-08 97
List of Tables
Table 2.1: Data exclusivity periods by country 39
Table 3.2: Success drivers and barriers in indication expansion 61
Table 3.3: Unmet needs prevalent within an indication 62
Table 3.4: Commercial considerations in prioritizing new indications 62
Table 3.5: Disease areas and related sub-populations for hypertension and heart failure 63
Table 3.6: New indication approvals by drug class, 1999-08 75
Table 4.7: FDC case studies 81