Pipeline Insight: Antihypertensives - Weak Pipeline Leaves Innovation To Novartis

Published by: Datamonitor

Published: Mar. 31, 2006 - 185 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

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)

Disclaimer

List of Tables

Table 1: Prevalence of hypertension in the seven major markets (000s), 2006-15

Table 2: Key global parameters of hypertension, 2002-15

Table 3: Pipeline drugs in development for hypertension, 2006

Table 4: Forecast key products in hypertension pipeline ($m)

Table 5: A comparison of the various forms of hypertension recognized by three of the key hypertension guidelines

Table 6: Unmet need comparators selected for baseline drug performance with weighting and score

Table 7: Quantitative measures used for clinical efficacy endpoints

Table 8: The antihypertensive R&D pipeline, 2006

Table 9: R&D approach to treating hypertension, 2006

Table 10: Phase of development of each treatment approach, 2006

Table 11: Composition of the antihypertensive R&D pipeline by company, 2006

Table 12: Antihypertensive late-stage pipeline, 2006 - drugs that act on the RAS

Table 13: Assumptions and events influencing Cardoxal's forecasts

Table 14: Assumptions and events influencing Clevelox's forecasts

Table 15: Assumptions and events influencing Rasilez's forecasts

Table 16: Selected published clinical trials for Rasilez (aliskiren)

Table 17: Assumptions and events influencing Rasilez's forecasts

Table 18: Assumptions and events influencing Rasilez's forecasts

Table 19: Pipeline ARB monotherapies, 2006

Table 20: Pipeline ARB combination therapies, 2006

Table 21: Pipeline renin inhibitors, 2006

Table 22: Pipeline angiotensin vaccines, 2006

Table 23: Pipeline vasopeptidase inhibitors, 2006

Table 24: Pipeline calcium channel blockers, 2006

Table 25: Pipeline endothelin receptor antagonists, 2006

Table 26: Forecast key products in hypertension pipeline ($m)

Table 27: Research, clinical and commercial attractiveness summary for key late-phase pipeline antihypertensive products

Table 28: Datamonitor drug assessment parameters

List of Figures

Figure 1: TypeFigTitleHere

Figure 2: Pipeline overview of antihypertensive drugs, 2006

Figure 3: Prevalence of hypertension broken down by age, 2004-15

Figure 4: Greatest unmet needs in hypertension, 2006

Figure 5: Baseline for drug comparison

Figure 6: Regulation of blood pressure

Figure 7: Treatment algorithm for hypertension

Figure 8: The renin-angiotensin system

Figure 9: Current pharmacological treatments for hypertension based on the inhibition of the RAS

Figure 10: ET-1 production by the vascular endothelium and its mechanism for producing vascular smooth muscle contraction

Figure 11: Endothelin receptors and the interaction with nitric oxide

Figure 12: Pipeline overview of antihypertensive drugs, 2006

Figure 13: The majority of patients need at least a combination of two antihypertensive drugs to reach target BP

Figure 14: Extent to which FDC would increase patient compliance in patients with hypertension and dyslipidemia only

Figure 15: Percentage of antihypertensive R&D projects in the various stages of development, 2006

Figure 16: Novartis's marketed and R&D antihypertensive portfolio, 2006

Figure 17: Developmental targets for the treatment of hypertension based on direct interaction with the renin-angiotensin system (RAS)

Figure 18: MATCHED study design

Figure 19: SWOT analysis for Cardoxal

Figure 20: Assessment of Cardoxal's performance indicators

Figure 21: Global sales forecast for Cardoxal ($m), 2006-15.

Figure 22: Phase III clinical development program for Clevelox

Figure 23: SWOT analysis of Clevelox

Figure 24: Assessment of Clevelox's performance indicators

Figure 25: Global sales forecast for Clevelox ($m), 2006-15.

Figure 26: SWOT analysis of CHF-1521

Figure 27: Assessment of CHF-1521's performance indicators

Figure 28: Global sales forecast for CHF-1521 ($m), 2006-15.

Figure 29: Study A1201; gross design and timeline

Figure 30: Blood pressure reductions reported from study A1201

Figure 31: Study A2308; gross design and timeline

Figure 32: Blood pressure reductions reported from study A2038

Figure 33: Systolic blood pressure (SBP) reductions during Novartis's SPP100 plus Diovan study (Study 2203)

Figure 34: Diastolic blood pressure (DBP) reductions during Novartis's SPP100 plus Diovan study (Study 2203)

Figure 35: Study A2204 - gross design and timeline

Figure 36: Study A2307; gross design and timeline

Figure 37: Study A2305; gross design and timeline

Figure 38: SWOT analysis of Rasilez

Figure 39: Assessment of Rasilez's performance indicators

Figure 40: Global sales forecast for Rasilez ($m), 2006-15.

Figure 41: SWOT analysis of Zanipress

Figure 42: Assessment of Zanipress's performance indicators

Figure 43: Global sales forecast for Zanipress ($m), 2006-15.

Figure 44: The olmesartan-based treatment algorithm

Figure 45: Blood pressure reductions in SHR rats (n=8) actively immunized with CYT006-AngQb

Figure 46: Research, clinical and commercial attractiveness summary for key late-stage antihypertensive pipeline products

Figure 47: Research, clinical and commercial attractiveness summary for key late-stage antihypertensive products

Figure 48: Example of Datamonitor drug assessment scorecard

Figure 49: An example drug assessment graph

Abstract

• 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

• 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

About MarketResearch.com
MarketResearch.com is an online aggregator selling over 160,000 market research reports, company profiles and country profiles from over 600 research firms. Our reports will provide you with the critical business and competitive intelligence you need for strategic planning and marketing research. Coverage includes the US, UK, Europe, Asia and global markets.