Market Report Source

Overview

Introduction
Datamonitor expects the antihypertensives market to reach almost $40 billion, across the seven major markets, by 2016. The growth will be driven by the uptake of Novartis’s Tekturna, as well as increased use of ARBs, and their combinations. However, the expiries of some key patents, particularly Pfizer’s Norvasc and Merck’s Cozaar, will restrain market growth.

Scope of this report

• Event-driven sales forecasts for 2007-16 across the seven major markets: US, France, Germany, Italy, Spain, UK and Japan.
• Country and market specific issues that will impact sales opportunities and market landscape, including key patent expiries and product launches.
• Case studies assessing the blockbuster potential of Novartis’s direct renin inhibitor, Tekturna, and the impact of ESC/ESH guideline reform in Europe.
• Comprehensive analysis of the current antihypertensives pipeline, including a clinical and commercial assessment of all key emerging therapies.

Research and analysis highlights
The growth rate of the antihypertensive market is declining. The market is mature and does not present an attractive opportunity for R&D expenditure; consequently Big Pharma are shying away from the pursuit of novel mechanisms of action in favour of developing more efficacious combination therapies.

Cozaar’s patent expiry in the US, has the potential to alter the structure of the antihypertensive market dramatically. Threats of generic substitution and money-saving healthcare strategies which have plagued other markets, are now approaching the successful ARB class, and will have an impact on the whole antihypertensive market.

Novartis is set to strengthen its position in the antihypertensives arena; Tekturna is expected to achieve international blockbuster status and Exforge will achieve sales of at least $800m, set back slightly by the premature expiry of Pfizer’s Norvasc patent.

Key reasons to read this report

• Quantify the future size of the antihypertensives market and identify opportunities for new products.
• Learn how recent European healthcare reforms and guideline updates will shape the antihypertensives market.
• Understand the barriers to uptake for novel antihypertensive agents, and the need for paradigm shift in clinical trial design.

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the cardiovascular pharmaceutical analysis team CHAPTER 1 EXECUTIVE SUMMARY Objective of the analysis Datamonitor insight into the hypertension market Contributing experts Related reports CHAPTER 2 MARKET DEFINITION AND OVERVIEW Definition of drug classes included Current market situation The antihypertensives market segmented by class The antihypertensives market segmented by country

Antihypertensive market landscape

Market growth and market restraint Factors driving growth of the antihypertensives market Factors restraining growth of the antihypertensives market Strategic scope and report focus US antihypertensives market dynamics Consideration of market unmet needs Conflicting evidence from clinical trials and guideline alterations Paradigm shift in antihypertensive R&D Defining the unmet need in the antihypertensives market Need beyond cosmetic blood pressure reduction

Improved diagnosis

Improved blood pressure management Increased uptake of fixed-dose combination therapies Targeting global cardiovascular risk and target organ damage Patient and primary care physician education CHAPTER 3 COUNTRY MARKET ASSESSMENTS Seven major market level assessment, opportunities and threats Market level assessment Opportunities Demographic and lifestyle trends continue to dominate the agenda, and have the potential to increase the hypertensive patient population Big Pharma cannot ignore the emerging markets of India and China Novel products are expected, but innovation is lacking in antihypertensive R&D Growing awareness of the metabolic syndrome Increasing co-operation between regulatory bodies Threats Increased generic competition Parallel trade Ongoing cost-containment measures Increasingly conservative regulatory environments Restrictive pricing and reimbursement policies Reduced periods of market exclusivity Mandatory registration of all clinical trial results

US: market level assessment, opportunities and threats

Market level assessment Opportunities

Direct-to-consumer (DTC) advertising is legal in the US and has been shown to influence patient prescription choice and increase diagnosis rates

Leveraging the JNC7 guidelines to maximize pharmacotherapy Price of drugs Threats The changing healthcare environment in the US will drive future generic use Medicare Part D is expected to lead to greater generic use Patient power Pharmaceutical re-importation issues continue to dog Big Pharma Formularies promote quality, but restrict choice Pricing and reimbursement issues Curbing of DTC advertising will lead to greater emphasis on risk of products Wal-Mart $4 a day generic program introduces further cost competition Japan: market level assessment, opportunities and threats Market level assessment Opportunities Ageing population An underdeveloped generics market slows brand erosion Possible introduction of direct-to-consumer advertising Multiple patent extensions and labeling regulations Opening up the Japanese market Drug approval lag-time being targeted by the Japanese Ministry of Health, Labor and Welfare Reduced product approval time Harmonization of approval process The Internet is an effective means to reach out to patients Threats Despite being underdeveloped, generics are expected to evolve into a significant player in the Japanese healthcare market in the future Flat sum reimbursement Complex regulatory process

Biannual price cuts still threaten market growth

New healthcare reforms under debate France: market level assessment, opportunities and threats

Market level assessment

Opportunities Innovation encouraged in the pharmaceutical industry Demographic changes provide opportunity for market expansion of chronic illnesses Consumers in France readily recognize the Internet as a source of high-quality medical information Generic consumption in France is particularly low Threats Continuation of cost-control measures Formulary access Take-off of generic sector Limitations on prescriptions dispensed from hospitals to patients in the community Pharmacists are being mandated to drive generic dispensing Germany: opportunities and threats Market level assessment Opportunities Pricing freedom which supports innovation ePharmacy and mail-order drugs legalized Threats Cost-containment measures in Germany have led to a healthy generics market German doctors set to receive bonuses for prescribing generics Italy: market level assessment, opportunities and threats

Market level assessment

Opportunities

Single agency holds regulatory authority

Negligible impact of generics is set to continue Threats Stringent reference pricing system Restructured reimbursement categories Intellectual property to conform with rest of EU Spain: market level assessment, opportunities and threats Market level assessment Opportunities Underdeveloped generics market both an opportunity and a threat Threats R&D activity expected to decline Reference pricing systems (RPS) likely to have an impact on branded revenues UK: market level assessment, opportunities and threats Market level assessment Opportunities NICE guidance advises against the use of beta-blockers GMS contact improvements Threats

Pharmaceutical Price Regulation Scheme (PPRS) implements periodic price cuts

Cost containment measures encourage continued high use of generics Summary of environmental issues affecting antihypertensive market size CHAPTER 4 PIPELINE DYNAMICS ANALYSIS Outlook for developmental antihypertensives Pipeline overview Pipeline agents by phase of development Pipeline antihypertensives segmented by mechanism of action Pipeline activity segmented by company Companies developing key novel antihypertensive agents

Novartis

Daiichi Sankyo Gilead Takeda CHAPTER 5 COMPARATIVE ASSESSMENT OF KEY PIPELINE PRODUCTS Overview Key pipeline product positioning Darusentan Mechanism of action Clinical assessment Commercial assessment Exforge (valsartan/amlodipine) Mechanism of action Clinical assessment Commercial Assessment Olmesartan/amlodipine Mechanism of action Clinical assessment Commercial Assessment Zanipress (enalapril/lercanidipine) Mechanism of action Clinical assessment

Commercial assessment

CYT006-AngQb Mechanism of action Clinical assessment Commercial assessment CHAPTER 6 FORECAST ANALYSIS Overview Changes in medical practice Increased use of ambulatory BP monitoring and home BP monitoring

Assessment of overall cardiovascular risk

Physician incentives to control blood pressure Pressure to increase compliance through the use of single-pill combination products Major clinical trials ONTARGET DREAM TROPHY Outcomes program for Rasilez: ALTITUDE, AVIATOR New product launches

Tekturna/Rasilez (aliskiren) marketed by Novartis

Exforge (valsartan+ amlodipine) marketed by Novartis Additional indications Irbesartan gains congestive heart failure indication Valsartan gains additional diabetes indication Micardis (telmisartan) gains type 2 diabetic nephropathy indication Patent expiries ARB patent expiries CCB patent expiries Betablocker patent expiries ACE inhibitor patent expiries Other patent expiries Data definitions, limitations and assumptions Standard units Japanese market data Derivation of sales forecasts and pricing trends Forecasts Forecast methodology CHAPTER 7 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDIES

Introduction

Case Study 1: Aliskiren – up to the hype? Introduction Mechanism of action Aliskiren Clinical development of aliskiren Key Phase III Trials with aliskiren

Aliskiren in combination with a diuretic

Aliskiren versus CCB and their combination Aliskiren versus ACEI and their combination Efficacy – As good, but no better Benign side-effect profile – Not good enough Long duration of action – The saving grace?

The negative-feedback conundrum

End organ protection Prevention of organ damage with ACEIs and ARBs Additional benefit from renin inhibition? Summary of key advantages: Can Novartis justify price premium? Datamonitor assessment Case study 2: ESC/ESH GUIDELINES Emphasis on the assessment of total cardiovascular risk Consideration of absolute risk versus relative cardiovascular risk Targeting end-organ damage Recommendation for lifestyle modification First-line treatment strategy Managing hypertension and comorbidities Treatment of specific patient groups Opinion leader SWOT analysis Strengths: Weaknesses: Potential barriers to uptake: Commercial implications and further work Implication for clinical trial design CHAPTER 8 BIBLIOGRAPHY AND REFERENCES Bibliography References APPENDIX A – MARKET DATA AND MAJOR BRAND FACTS

Mechanisms of action

Beta blockers

Calcium channel blockers Diuretics Angiotensin converting enzyme inhibitors Angiotensin-II receptor blockers (ARBs) Seven major market antihypertensive market data Segmentation by country Segmentation by class Major brand facts C7 Betablockers C8 Calcium channel blockers C9 Angiotensin converting enzyme inhibitors C9 Angiotensin II receptor blockers Anatomical Therapeutic Chemical (ATC) classification

APPENDIX B – MARKET FORECAST DATA

US Forecasts

Japan Forecasts

France Forecasts Germany Forecasts Italy Forecasts Spain Forecasts UK Forecasts Report methodology About Datamonitor About Datamonitor Healthcare About the cardiovascular disease analysis team Disclaimer List of Tables

Table 1: Seven major market antihypertensive sales ($m), 2006.

Table 2: Sales of antihypertensives across the seven major markets by country Sales of Antihypertensives by Country($m), 2006. Table 3: Seven major market sales and market share of the 10 top-selling antihypertensives, 2006

Table 4: Prevalence of obesity in the seven major markets by age (000s), 2003 (all totals have been rounded where applicable)

Table 5: US antihypertensive sales, 2006 Table 6: Five generics companies are among the top 10 companies in terms of prescriptions filled under Medicare Part D, 2006 Table 7: The actual generic fill rate varies between therapeutic classes, 2006 Table 8: Wal-Mart is selling many generic antihypertensives for less than the mean price per standard unit in the US in 2006 Table 9: Japan antihypertensive sales, 2006 Table 10: An example of the savings to be realized by using generic drugs in the Japanese market, 2006 Table 11: France antihypertensive sales, 2005 Table 12: Germany antihypertensive sales, 2005 Table 13: Italy antihypertensive market, 2006 Table 14: Spain antihypertensive market, 2006 Table 15: UK antihypertensive market, 2006 Table 16: The 10 clinical areas of the Quality Outcome Framework, as outlined in the GMS contract, 2005 Table 17: Summary of macro-environmental issues affecting the antihypertensive market, 2007 Table 18: The antihypertensive R&D pipeline, 2007 Table 19: Patent expiry dates used in forecasting the antihypertensive market across the seven major markets, 2007-2016 Table 20: Effects of Circulating RAS and Tissue RASe Table 21: Kredex: key facts

Table 22: Toprol-XL: key facts

Table 23: Tenormin; key facts Table 24: Inderal: key facts Table 25: Norvasc: key facts Table 26: Plendil: key facts Table 27: Cardizem LA: key facts Table 28: Adalat: key facts Table 29: Altace: key facts

Table 30: Aceon: key facts

Table 31: Accupro: key facts Table 32: Atacand; key facts Table 33: Teveten: key facts Table 34: Avapro: key facts Table 35: Cozaar: key facts Table 36: Benicar: key facts Table 37: Micardis: key facts Table 38: Diovan: key facts Table 39: Antihypertensive classifications Table 40: US Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 41: Japan Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 42: France Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 43: Germany Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 44: Italy Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 45: Spain Antihypertensives $ (000s)Sales Forecast 2006-2016 Table 46: US Antihypertensives $ (000s)Sales Forecast 2006-2016 List of Figures

Figure 1: Growth in the antihypertensives market by country, 2003-06

Figure 2: Proportion of population aged 20-39 years, 2004 and 2015, and prevalence of hypertension in this age group in the seven major markets, 2004 Figure 3: Proportion of population aged 40-59 years, 2004 and 2015, and prevalence of hypertension in this age group in the seven major markets, 2004 Figure 4: Proportion of population aged 60-79 years, 2004 and 2015, and prevalence of hypertension in this age group in the seven major markets, 2004 Figure 5: The growing prevalence of obesity in the US, 2005-2015 Figure 6: Generalized distribution chain for parallel traded pharmaceutical products Figure 7: JNC6 and JNC7 compared: classification of blood pressure levels Figure 8: Compelling indications for individual drug classes Figure 9: More than half of all prescriptions dispensed in the US are generics, 1994-2005 Figure 10: Generic companies dominate the US pharmaceutical market in terms of prescriptions Figure 11: Generic use in the US is promoted through a number of channels Figure 12: The generic fill rates in the US for 2003 varied considerably by state

Figure 13: The tiered co-payment system will lead to greater use of generics

Figure 14: Key pressures facing drug developers, 1990-2004

Figure 15: Wal-Mart’s $4 generic drug program web-page

Figure 16: The Japanese generic market is underdeveloped because of a number of factors Figure 17: Pipeline antihypertensive agents segmented by phase of development, 2007 Figure 18: Pipeline antihypertensive agents segmented by mechanism of action, 2007

Figure 19: The nature of the compounds in the antihypertensives pipeline, 2006

Figure 20: Nature of antihypertensive developmental compounds according to company type, 2007 Figure 21: Pipeline maturity index for antihypertensive agents, 2007 Figure 22: Comparative assessment of pipeline antihypertensive agents Figure 23: Segmentation of the antihypertensives market by country, 2007

Figure 24: Segmentation of the antihypertensives market by class, 2007