Market Report Source

Overview

Introduction
Despite modest improvements in blood pressure control, effective blood pressure control for all still seems to be an elusive goal. As such, the promotion and use of combination therapies has increased, explaining much of the current R&D activity in this area where many developers are studying novel combinations of currently marketed drugs rather than discovering innovative treatments

Scope
Evaluation of patient potential for developmental antihypertensives over the period 2006-2015
Scrutiny of key impacts on the R&D approach and cost, evaluation of optimal clinical trial end points and identification of suitable comparators
Evaluation of key players in the hypertensive market and opposing company approaches to development and commercialization
Analysis of key antihypertensive drugs in development and their ability to satisfy major unmet needs and compete with existing agents

Highlights
The use of fixed dose combination (FDC) therapy will continue to grow substantially over the forecast period, exceeding the growth of single pill alternatives. Despite FDCs forming an essential part of a strategy for controlling hypertension, their development is starving innovation within antihypertensive R&D

Rasilez, the only real innovation in the current pipeline, will be the first oral renin inhibitor to be launched. Its ability to proximally block the renin angiotensin system (RAS), combined with its true 24-hour activity, means it may offer specific advantages over other drug classes, and is likely to become a blockbuster by 2010

Despite continued research into other hypertension targets such as endothelin and vasopeptidase poor safety records, lack of efficacy compared to other classes and a low patient potential, these agents promise to be no more than an academic interest rather than providing physicians with a real alternative in treating hypertension

Reasons to Purchase
Understand physician sentiment on renin inhibitors as the next innovative drug class, and the threats faced by existing and developmental products
View independent sales forecasts for products in late stage development for treatment of hypertension in both existing and novel classes
Identify early stage antihypertensive compounds with high potential being developed by companies seeking a marketing partner”

Table of Contents

TABLE OF CONTENTS

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Historical perspective of the antihypertensives market

Datamonitor insight into the antihypertensive market

Unlike many other disease areas, opinion is significantly divided on the identity of a “gold standard therapy” for the treatment of hypertension, with all of the currently available drug classes satisfying at least some of the needs of the hypertensive patient.

Lifecycle management strategies dominate antihypertensive R&D, with nearly half of all development projects assessing the safety and efficacy of novel combinations of currently marketed antihypertensive drugs. As such, innovation seen in other disease areas is scarce in antihypertensive R&D.

What innovation exists is being single-handedly delivered by Novartis, who is developing Rasilez (aliskiren), a first-in-class drug of the new orally active renin inhibitors. With its distal blockade of the renin-angiotensin system (RAS), compared to the proximal blockade provided by the ACEs and ARBs, Rasilez has the potential to offer superior blockade of the RAS, with enhanced end-organ protection compared to other classes the drug’s most promising attribute.

Despite continued research into other hypertension targets – such as endothelin and vasopeptidase – a poor safety records, lack of efficacy compared to other classes and a low patient potential, these agents promise to be no more than an academic interest rather than providing physicians with a real alternative in treating hypertension.

Summary

Key metrics

CHAPTER 2 PATIENT POTENTIAL

Definition of the hypertension market

Definition of hypertension

Treatment goals in hypertension

Segmentation of hypertension

Diabetic hypertensive patients

Hypertensives with renal disease

Isolated systolic hypertension (ISH)

Epidemiology, diagnosis and treatment

Epidemiology

Future trends in the prevalence of hypertension

Diagnosis and treatment rates

Methodology

The US

Japan

France

Germany

Italy

Spain

The UK

Summary

Unmet needs in the treatment of hypertension

Unmet need 1 – increased efficacy in reducing SBP

Unmet need 2 – increased use of FDCs

Unmet need 3 – improved compliance

Unmet need 4 – greater choice of two- or three-drug combinations

Other potential unmet needs

Greater patient involvement in therapy

Cognitive function, vascular fibrosis and antiplatelet effects

Comparators used to assess each criterion

CHAPTER 3 R&D APPROACH

Normal blood pressure maintenance …

… and where things go wrong

Current treatment approaches: a holistic approach

Principles of antihypertensive pharmacotherapy

Is there a gold standard antihypertensive pharmacotherapy?

Current pharmacological treatment options in hypertension

Drugs that inhibit the renin-angiotensin system

Angiotensin converting enzyme inhibitors (ACEs)

Angiotensin receptor blockers (ARBs)

Beta-blockers (BBs)

Drugs that do not inhibit the renin-angiotensin system

Calcium-channel blockers

Diuretics

Other classes of antihypertensive therapy

Centrally acting agents

Alpha blockers

Classification of pipeline products

Novel targets for the treatment of hypertension

Endothelin receptor antagonists (ERAs)

Neutral endopeptidase inhibitors (NEPs)

Renin inhibitors

Vaccines against components of the RAS

Vasopeptidase inhibitors (VEPs)

Clinical trial design in hypertension

Mortality endpoints

Adequately powered

Significant numbers of each sub-population

Use of the gold standard as comparator drug

Morbidity endpoints

Trials conducted in patients uncontrolled on multiple drug therapy

Use of surrogate markers

Key research impacts on hypertension

Outcome-based endpoints

Impact of clinical trial duration on R&D budget

CHAPTER 4 ANTI-HYPERTENSIVE PIPELINE ANALYSIS

Pipeline summary

Lifecycle management vs innovation

Lifecycle management strategies

Innovation – scarce, but biotechs continue to “think outside of the box”

Vaccines – surprise pipeline projects

Greatest number of drugs in Phase II of development

Key companies involved in antihypertensive R&D

Novartis – leading the way

Pfizer – a notable absentee

CHAPTER 5 ANTI-HYPERTENSIVE LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview

Late-stage pipeline drugs to be analyzed

Definition of current comparator therapy

Cardoxal (MC-1 cardioprotectant plus lisinopril)

Drug overview

Key pre-clinical data

Clinical trial data

Author’s comments

Datamonitor’s comments

Marketing factors

Patient potential

SWOT analysis of Cardoxal

Performance against benchmark criteria

Forecasts for 2015

Clevelox (clevidipine)

Drug overview

Clinical trial data

Marketing factors

Patient potential

SWOT analysis of Clevelox

Performance against benchmark criteria

Forecasts for 2015

CHF-1521 (manidipine plus delapril)

Drug overview

Clinical trial data

Datamonitor’s comments

Marketing factors

Patient potential

SWOT analysis of CHF-1521

Performance against benchmark criteria

Forecasts for 2015

Rasilez (aliskiren)

Drug overview

Clinical trial data

Authors’ comments

Datamonitor’s comments

Marketing factors

Patient potential

SWOT analysis of Rasilez

Performance against benchmark criteria

Forecasts to 2015

Zanipress (lercanidipine plus enalapril)

Drug overview

Clinical trial data

Datamonitor’s comments

Marketing factors

Patient potential

SWOT analysis of Zanipress

Performance against benchmark criteria

Forecasts to 2015

Other development compounds

Drugs that inhibit the renin-angiotensin system (RAS)

Angiotensin receptor blockers (ARBs) monotherapies and combination therapies

Renin inhibitors

Vaccines against components of the RAS

Vasopeptidase inhibitors (VEPs)

Drugs that do not inhibit the renin-angiotensin system

Calcium channel blockers

Endothelin receptor antagonists (ERAs)

Comparative forecasts

Comparative analysis

APPENDIX A

Methodology

Datamonitor forecast methodology

The forecasting model

General event information

Event selection and quantification

Datamonitor drug assessment summary

Contributing experts

References

Report methodology

APPENDIX B

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s therapy area capabilities

About the Cardiovascular analysis team

Key therapy team members

Dr Allison Fleetwood, Director, Cardiovascular, Diabetes and Women’s Health

Dr Duncan Emerton, Senior Analyst, Cardiovascular (report author)

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