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

This report investigates three goals in optimizing				Data exclusivity in the context of biologics 44
product potential- expanding the drug's patent				Chapter 3 Accessing broader patient populations 46
protected lifespan, accessing broader patient				Summary 46
populations and launching line-extensions via fixed				Drug labeling and market access 47
dose combinations. The key success factors in each				Off-label drug usage 47
of these pursuits have been clearly identified,				Commercial incentives and disincentives 48
emerging trends have been presented and the				Payors stance on off-label reimbursement 49
underlying concepts have been explained to provide a				Case study: Avastin and Lucentis 51
clear understanding of current industry dynamics.				Expanding the label 53
Case studies on popular products have been used to				Role in product lifecycle management 53
illustrate these concepts in the real world. An in-depth				New indications 53
analysis of drug approval data provides context for				Pediatric extensions and special populations 54
the issues discussed. This information is juxtaposed				Modified indications and expanded usage 54
with historic sales data to explore the correlation				Case study: Yaz 55
between the strategies employed and revenue				Case study: Remicade 58
potential.				Indication expansion 59
This report explains the basics of drug lifecycle and				Choosing the primary indication 61
investigates three goals in optimizing product				Related versus unrelated indications 63
potential- expanding the drug's patent protected				Sequence of indication expansion 64
lifespan, accessing broader patient populations and				Timing of indication expansion 65
launching line-extensions via FDCs.				Launching early in commercial lifecycle 68
The key success factors in each of these pursuits				Launching late in commercial lifecycle 69
have been clearly identified, emerging trends have				Seroquel: Using indication expansion and drug
been presented and the underlying concepts have				reformulation synergistically 70
been explained to give the reader a clear				Recent trends in indication expansion 72
understanding of current industry dynamics. Case				Indication expansion for NDAs 72
studies on popular products have been used to				Indication expansion for biologics 75
illustrate these concepts in the real world.				Chapter 4 Fixed dose combinations 80
An in-depth analysis of drug approval data provides				Summary 80
context for the issues discussed. This information is				Introduction 81
juxtaposed with historic sales data to explore the				Clinical challenges in FDC development 81
correlation between the strategies employed and				FDC patents 82
revenue potential.				Data exclusivity for FDCs 83
Key findings				Role in product lifecycle maximization 83
Drug manufacturers must make the best strategic				Case study: Advair's role in GSK's asthma franchise
use of the patent-protected lifespan of a drug, or				85
else risk losing the profit incentives they perceived at				Case study: How Vytorin influenced Zocor's patent
the start of the project. (Ch. 1)				expiry 88
In light of the increasing complexity of				Case study: BiDil's value proposition reinvented 90
biopharmaceutical patenting, the ‘freedom to				FDC uptake by geography 91
operate', i.e. to commercialize the invention, is coming				Case study: FDCs for hypertension 91
under increasing scrutiny. (Ch. 2)				Clinical rationale 93
The US Congress' emerging stance on data				Synergistic efficacy or safety 94
exclusivity provisions for biologics will define the				Easier Rx management 95
length of time a biotechnology company can keep				Correlation between FDC usage and drug compliance
out generic competition in new indications. The				95
biotech industry's stance is that the current provisions				Correlation between drug compliance &
do not provide for enough time to profit from their				improved clinical outcomes 96
post-approval R&D investments. (Ch. 2)				FDC usage by therapy area 96
The potential for post-approval label expansion is				Key success factors and competitive hurdles 98
much greater for biologics in comparison to small				Endorsement by treatment guidelines 98
molecule pharmaceutical drugs. Most biologics on the				Perceived synergy effects over free combination 99
market today can expect to add significant revenue				Compliance advantage over the free combination 99
streams via new indications, and potentially extend				Usage of mono compounds prior to FDC launch 99
their commercial lifespan. (Ch 3)				Discount compared to cheapest free combination 100
Over 45% of all new indication approvals granted by				Time-to-LOE of parent brand 101
the FDA since 1998 belong to drugs that fall in the				Chapter 5 Appendix 103
Genito-urinary system and Nervous system.				Primary research methodology 103
If an FDC is launched close to the loss of exclusivity				Glossary 107
date of the constituent brand, it may be interpreted				Index 111
as a marketing tactic to limit post-LoE revenue losses.				List of Figures
If launched early, it may show intent to cater to a				Figure 1.1: Summary of lifecycle of medicinal drugs 17
genuine unmet need, or to legitimately maximize the				Figure 1.2: Transition probabilities for clinical phases 18
potential of the parent molecule(s). (Ch. 4)				Figure 1.3: Out-of-pocket and capitalized costs of
Scope of the report				developing a drug ($m) 19
In-depth case studies explore the real-world				Figure 1.4: Time taken for development of new
execution of the issues and challenges discussed in				pharma & biotech drugs 20
the report.				Figure 1.5: Approval timelines at CDER for priority
Analysis of historic drug approval data provides the				NDAs, 1999-08 21
reader with contextual reference points.				Figure 1.6: Approval timelines at CDER for standard
Case studies on Vytorin, Advair and BiDil illustrate the				NDAs, 1999-08 21
strategies employed by three leading FDC brands.				Figure 1.7: Imperatives of efficient lifecycle
Brand histories of Yaz, Remicade and Seroquel show				management 23
how label expansion is fundamental to successful				Figure 1.8: Increasing importance of payors as
lifecycle management.				stakeholders 24
Where applicable, these strategies are discussed with				Figure 1.9: Tougher payor environments are slowing
reference to specific therapeutic areas or				product uptake 25
geographies.				Figure 1.10: Therapeutic substitution and formulary
Issues related to biologics are highlighted to indicate				access 27
where they differ from small molecule drugs.				Figure 2.11: 8+2+1 data exclusivity system in Europe
Use this report to				41
Gain an understanding of legal provision for patent				Figure 2.12: Data exclusivity and patent protection in
protection and data exclusivity. Understand their role				the US 43
in the context of product lifecycle management				Figure 3.13: On and off-label decision making by
Utilize the historical data on NDA approvals to identify				payors 50
trends and build assumptions into competitive				Figure 3.14: Off-label usage of Avastin: a
landscape forecasts.				pharmacoeconomic model for wet AMD 52
Understand the stance of key stakeholders and				Figure 3.15: Yaz: Label expansion & sales growth
implications of off-label drug usage.				- US ($m), 2006-08 57
Understand the role of FDCs in optimizing the				Figure 3.16: Remicade: Label expansion & sales
commercial potential of a product asset, and the main				growth - US ($m), 2001-08 59
challenges in their commercialization				Figure 3.17: Time between launch of original and new
Juxtapose historic sales performance with the timing				indications in the US (by ATC), 1999-08 66
of indication expansion and FDC based strategies to				Figure 3.18: Time between launch of original and new
assess the success or failure				indications in the US (by ATC), 1999-08 (contd) 67
				Figure 3.19: Considerations in launching new indications
				early in the lifecycle 69
				Figure 3.20: Considerations in launching new indications
Table of Contents :				late in the lifecycle 70
				Figure 3.21: Lifecycle management: Seroquel and
Optimizing Lifecycle Management				Seroquel XR 71
Executive summary 8				Figure 3.22: New indication approvals for NDAs,
Product lifecycle and management challenges 8				1999-2008 73
Influencing the commercial lifespan of the drug 9				Figure 3.23: New indication approvals for Orphan
Accessing broader patient populations 10				drugs, 1999-08 73
Fixed dose combinations 11				Figure 3.24: New indication approvals with priority
Chapter 1 Product lifecycle and management				reviews, 1999-08 74
challenges 14				Figure 3.25: Increasing clinical and commercial potential
Summary 14				for Remicade 77
Introduction 15				Figure 4.26: FDC approvals in the US, 1999-08 84
The lifecycle of biopharmaceutical drugs 15				Figure 4.27: Advair: FDA approvals and patent
Development lifecycle 17				protection 86
Commercial lifecycle 22				Figure 4.28: Advair-Serevent sales in the US:
Managing the lifecycle 22				maintaining revenues post patent expiry of Flovent
Longer development time 23				87
Slower product uptake via reimbursement hurdles 24				Figure 4.29: Zocor-Vytorin-Zetia brand timeline 88
Peak sales potential is reduced by higher competition				Figure 4.30: Cushioning the patent cliff:
25				Zocor-Vytorin-Zetia sales in US ($m), 2001-08 89
Earlier lifecycle decline due to therapeutic substitution				Figure 4.31: FDC usage for hypertension across major
26				markets 93
Chapter 2 Influencing the commercial lifespan of a				Figure 4.32: Drug classes with maximum FDC
drug 30				approvals in the US, 1999-08 97
Summary 30				List of Tables
Bargaining power of biopharmaceutical brands 31				Table 2.1: Data exclusivity periods by country 39
Brand equity 31				Table 3.2: Success drivers and barriers in indication
Patent protection and "freedom to operate" 32				expansion 61
Strategic patenting 33				Table 3.3: Unmet needs prevalent within an indication
Patent prosecution superhighway 35				62
Patent protection for biologics 35				Table 3.4: Commercial considerations in prioritizing new
Data exclusivity 36				indications 62
Difference between data exclusivity and patent				Table 3.5: Disease areas and related sub-populations
protection 40				for hypertension and heart failure 63
8+2+1 system in the EU 40				Table 3.6: New indication approvals by drug class,
Data exclusivity in the US 42				1999-08 75
Data exclusivity in Japan 43				Table 4.

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