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Cardiovascular Drug Discoveries 2008

Published by: Espicom Healthcare Intelligence

Published: Apr. 30, 2008 - 314 Pages


Table of Contents


Foreword

Executive Summary

Cardiovascular Disease

Mortality

Prevention and Treatment

Drugs in the Pipeline

Competitor Ratio Analysis

Cholesterol and Triglycerides

The Cholesterol Management Drugs Market

Statins

NICE Guidance on the use of statins

Lipitor (atorvastatin)

Patents, Generic Competition & Litigation

US

Canada

Austria

Denmark

Finland

Ireland

Norway

Spain

UK

Australia

Andean Pact countries

Sales Forecast

Clinical Trials

SPARCL

Imaging studies: ILLUSTRATE and RADIANCE

Pfizer’s response to the ASTEROID trial

TNT

ASCOT

ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial: Lipid-Lowering Arm)

CARDS

IDEAL - atorvastatin versus simvastatin

Atorvastatin+rosiglitazone in diabetic patients

Lescol (fluvastatin)

Patents & Generic Competition

Sales Forecast

Clinical Trials

ALERT

LIPS

Crestor (rosuvastatin)

Patents, Generic Competition & Litigation

Safety Issues

Patient data demonstrate efficacy of Crestor

Sales Forecast

Clinical Trials

ASTEROID

METEOR

MERCURY II

EXPLORER

Effect of rosuvastatin on C-reactive protein and renal function

Crestor in combination with ezetimibe

LDL-C reductions - Crestor versus Pravachol and Zocor

Zocor (simvastatin)

Generic Competition

Sales Forecast

Clinical Trials

SAFARI - simvastatin+fenofibrate

4S

Heart Protection Study

Other Antihyperlipidaemic Agents

Zetia (ezetimibe)

NICE guidance on ezetimibe

Patents, Generic Competition & Litigation

Sales Forecast

Clinical Trials

EXPLORER

Co-administration of ezetimibe+fenofibrate

EASE

TriCor (fenofibrate)

Patents, Litigation & Generic Competition

Lipofen (fenofibrate)

Fenoglide (fenofibrate)

Sales Forecast

Clinical Trials

TriCor (fenofibrate) & WelChol (colesevelam)

Niaspan (niacin)

Patents & Litigation

Sales Forecast

Clinical Trials

Niaspan combined with aspirin

COMPELL

Combination Products

Vytorin (ezetimibe+simvastatin)

FDA issues early communication regarding ongoing review of Vytorin

Patents

Sales Forecast

Clinical Trials

ENHANCE

IMPROVE-IT

Vytorin versus Lipitor (atorvastatin) in Type II diabetes patients

Combined post hoc analysis of three studies

VYVA

Caduet (amlodipine+atorvastatin)

Patents & Generic Competition

Sales Forecast

Clinical Trials

GEMINI AALA

JEWEL

Recent Approval and Drugs in Development

Simcor

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

SEACOAST

Tredaptive (niacin+laropiprant)

Competitor ratio analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Phase III

Tredaptive co-administered with simvastatin

MK-0524B (simvastatin+niacin+laropiprant)

Competitor ratio analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

MK-0452B versus atorvastatin

MK-0452B versus MK-0452A+simvastatin

TriLipix (ABT-335)

Competitor ratio analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Anacetrapib

Competitor ratio analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Outlook

Clinical Trials

Phase IIb

Phase I

AEGR-733

Competitor ratio analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Outlook

Clinical Trials

Phase II

Homozygous Familial Hypercholesterolaemia

Hypertension

The Hypertension Drugs Market

Angiotensin-II Receptor Blockers

Aprovel (irbesartan)

Patents & Generic Competition

Sales Forecast

Clinical Trials

INCLUSIVE

COSIMA

Diovan/Co-Diovan (valsartan/valsartan+HCTZ)

Patents, Generic Competition & Litigation

Sales Forecast

Clinical Trials

NAVIGATOR

AADVANCE

VALUE

Val-HeFT

Cozaar/Hyzaar (losartan/losartan+HCTZ)

Patents & Generic Competition

Sales Forecast

Clinical Trials

LIFE

ELITE II

Micardis/MicardisPlus (telmisartan/telmisartan+HCTZ)

Patents & Generic Competition

Sales Forecast

Clinical Trials

SURGE-2

PRISMA

ONTARGET/TRANSCEND

PROTECTION

PROTECTION Study Programme - AMADEO

PROTECTION Study Programme - DETAIL

PROTECTION Study Programme - ESPRIT

PROTECTION Study Programme - ATHOS

PROTECTION Study Programme - INNOVATION

Atacand (candesartan cilexetil)

Patents & Generic Competition

Sales Forecast

Clinical Trials

HIJ-CREATE

TROPHY

CHARM

DIRECT

Switching from losartan to candesartan cilexetil: an observational study in the UK

Benicar (olmesartan)

Patents & Generic Competition

Sales Forecast

Clinical Trials

MORE

BEST & Treatment of Stage I and Stage II Hypertension Studies

Dihydropyridine Calcium Channel Blockers

Norvasc (amlodipine)

Patents & Generic Competition

Sales Forecast

Clinical Trials

ASCOT

CAFE

Adalat (nifedipine)

Patents & Generic Competition

Sales Forecast

Clinical Trials

TALENT

ACTION

Zanidip (lercanidipine)

Sales Forecast

ACE Inhibitors

Vasotec (enalapril)

Generic Competition

Sales Forecast

Altace/Delix/Tritace (ramipril)

Combinations

Patents & Generic Competition

Sales Forecast

Clinical Trials

Altace+HCTZ

Beta Blockers

Coreg (carvedilol)

OPTIMIZE-HF

Patents & Generic Competition

Sales Forecast

Clinical Trials

MUCHA

COMET

COPERNICUS

Seloken/Toprol-XL (metoprolol succinate)

Patents & Generic Competition

Sales Forecast

Clinical Trials

POISE

Alpha Adreno-Receptor Antagonists

Cardura (doxazosin)

Sales Forecast

Combination Products

Lotrel (amlodipine+benazepril)

Patents & Generic Competition

Sales Forecast

Clinical Trials

ACCOMPLISH

LOGIC, SHIELD and ALERT

Azor (amlodipine+olmesartan)

Zanipress (lercanidipine+enalapril)

Recent Approvals and Drugs in Development

Rasilez/Tekturna (aliskiren)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

ALLAY

Phase III Results

Phase II Results

Bystolic (nebivolol)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Bystolic in African-American patients with Stage I-II HT

Patients with mild-to-moderate HT

Darusentan

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

DAR-201

Cleviprex (clevidipine)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

VELOCITY

ECLIPSE

Ilepatril

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Coronary Artery Disease

Genetic variations may increase risk of CAD

Angina

Recent Approvals and Drugs in Development

Crestor: first statin to achieve atherosclerosis regression by QCA in a major clinical trial

Ranexa (ranolazine)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Ranolazine in LQT3

MERLIN TIMI-36

ERICA

CARISA

MARISA

Procoralan (ivabradine)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Procoralan versus amlodipine in patients with stable CAD

BEAUTIFUL

Generx (alferminogene tadenovec, Ad5FGF-4)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Clinical Trials

AWARE

AGENT-3, AGENT-4

Experimental Stem Cell Therapy

Atrial Fibrillation

Current Treatments

Cordarone (amiodarone)

Rythmol (propafenone)

Tambocor (flecainide)

Corvert (ibutilide fumarate)

Tikosyn (dofetilide)

Clinical Trials

DIAMOND

Drugs in Development

Multaq (dronedarone)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

EURIDIS and ADONIS

Pulzium (tedisamil)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Vernakalant (RSD1235)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

ACT 1

ACT 3

Phase IIb study of oral vernakalant

Pulmonary Arterial Hypertension

Tracleer (bosentan)

Sales Forecast

Clinical Trials

COMPASS-1 and EARLY

BUILD Programme

BREATHE-5

Paediatric Study

TRAX PMS

Ventavis (iloprost)

Sales Forecast

Clinical Trials

VISION

STEP

Long-term safety and efficacy

ACTIVE

Revatio (sildenafil)

Sales Forecast

Clinical Trials

Australian Trial in Heart Failure

Thelin (sitaxsentan)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Eisenmenger syndrome - observational data

Long-term treatment

STRIDE-2

STRIDE-2X

STRIDE-4

Letairis/Volibris (ambrisentan)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

ARIES

AMB-222

Viveta (treprostinil)

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Clinical Trials

Treprostinil in AERx Essence delivery system

TRIUMPH-1

Inhaled treprostinil as add-on therapy

Thrombosis

The Thrombosis Drugs Market

Lovenox (enoxaparin)

Patents & Generic Competition

Sales Forecast

Clinical Trials

ExTRACT-TIMI 25

STEEPLE

SYNERGY

Arixtra (fondaparinux)

Patents & Generic Competition

Sales Forecasts

Clinical Trials

OASIS- 5

OASIS 6

ARTEMIS

FLEXTRA

PEGASUS

Plavix (clopidogrel)

Patents & Generic Competition

Sales Forecast

Clinical Trials

Individualised loading study

BRAVE-3

CHARISMA

ACTIVE

Recent Approval and Drugs in Development

Pradaxa (dabigatran)

Competitor Ratio Analysis

7Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

RE-VOLUTION (RE-MODEL, RE-MOBILIZE and RE-NOVATE)

Prasugrel

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

TRITON-TIMI 38

Early-phase data

Rivaroxaban

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

RECORD2

RECORD3

Phase ll studies

Apixaban

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Sales Forecast

Clinical Trials

Phase II

M118

Competitor Ratio Analysis

Novelty/rationale for mechanism of action

Proof of concept/clinical data

Management/clinical expertise

Competition within the marketplace

Risks associated with drug development in therapeutic class

Clinical Trials

Phase II

Phase I

Abbreviations

SOURCES

Espicom Sources

Others

List of Tables

Deaths from Ischaemic Heart Diseases in Selected Markets, 2005

Deaths from Acute Myocardial Infarction in Major Markets, 2005

Deaths from Diseases of the Pulmonary Circulation and Other Forms of Heart Disease, 2005

Leading Cardiovascular Drugs by Sales Value, 2006-2007 (US$ Million)

US Patent Expiry for Major Cardiovascular Drugs

Launched Products in Development

Novel Drugs in Development

Competitor Ratio Analysis Summary

Sales of Leading Cholesterol Management Drugs, 2006-2007 (US$ Million)

Sales of Leading Statins, 2003-2007 (US$ Million)

Lipitor Sales, 2003-2012 (US$ Million)

Lipitor US Patents

Lescol Sales, 2003-2007 (US$ Million)

Lescol US Patents

Crestor Sales, 2003-2007 (US$ Million)

Crestor US Patents

Zocor Sales, 2003-2007 (US$ Million)

Zetia Sales, 2003-2007 (US$ Million)

Zetia US Patents

TriCor Sales, 2003-2007 (EUR & US$ Million)

TriCor US Patents

Niaspan Sales, 2003-2007 (US$ Million)

Niaspan US Patents

Vytorin Sales, 2004-2007 (US$ Million)

Vytorin US Patents

Caduet Sales, 2004-2007 (US$ Million)

Caduet US Patents

Drugs in Development for Hypercholesterolaemia and Dyslipidaemia

Sales of Leading Hypertension Drugs, 2006-2007 (US$ Million)

Aprovel/Avapro/Karvea Sales, 2003-2007 (EUR & US$ Million)

Avapro/Avalide US Patents

Diovan/Co-Diovan Sales, 2003-2007 (US$ Million)

Diovan US Patents

Cozaar/Hyzaar Sales, 2003-2007 (US$ Million)

Cozaar/Hyzaar US Patents

Micardis Sales, 2003-2007 (EUR & US$ Million)

Micardis Sales in Japan, 2003-2007 (¥ & US$ Million)

Micardis US Patents

Atacand Sales, 2003-2007 (US$ Million)

Blopress Sales, 2003-2007 (¥ Billion & US$ Million)

Atacand/Atacand Plus US Patents

Benicar/Olmetec Sales, 2004-2007 (¥ Million & US$ Million)

Benicar US Patents

Norvasc Sales, 2003-2007 (US$ Million)

Amlodin Sales, 2003-2007 (¥ Billion & US$ Million)

Adalat Sales, 2003-2007 (EUR & US$ Million)

Adalat US Patents

Zanidip Sales, 2003-2007 (EUR & US$ Million)

Vasotec/Vaseretic Sales, 2003-2007 (US$ Million)

Altace/Delix/Tritace Sales, 2003-2007 (EUR & US$ Million)

Altace US Patents

Coreg/Dilatrend Sales, 2003-2007 (£/CHF & US$ Million)

Coreg US Patents

Seloken ZOK/Toprol-XL Sales, 2003-2007 (US$ Million)

Cardura Sales, 2003-2007 (US$ Million)

Lotrel Sales, 2003-2007 (US$ Million)

Lotrel US Patents

Drugs in Development for Hypertension

Drugs in Development for Atherosclerosis and Coronary Artery Disease

Drugs in Development for Atrial Fibrillation

Drugs in Development for PAH

Tracleer Sales, 2003-2007 (CHF & US$ Million)

Sales of Leading Anticoagulant & Antiplatelet Drugs, 2006-2007 (US$ Million)

Lovenox/Clexane Sales, 2003-2007 (EUR & US$ Million)

Lovenox US Patents

Arixtra Sales, 2004-2007 (£ & US$ Million)

Plavix/Iscover Sales, 2003-2007 (EUR & US$ Million)

Plavix US Patents

Drugs in Development for Thrombosis

List of Figures

Global Sales of Leading Statins, 2003-2007 (US$ Million)

Lipitor Sales, 2003A-2012E (US$ Million)

Lescol Sales 2003A-2012E (US$ Million)

Crestor Sales, 2003A - 2012E (US$ Million)

Zocor Sales 2003A-2012E (US$ Million)

Zetia Sales 2003A-2012E (US$ Million)

TriCor Sales, 2003A-2012E (US$ Million)

Niaspan Sales, 2003A - 2012E (US$ Million)

Vytorin Sales, 2004A-2012E (US$ Million)

Caduet Sales 2004A-2012E (US$ Million)

Simcor Projected Sales, 2008-2012 (US$ Million)

Tredaptive Projected Sales, 2008-2012 (US$ Million)

MK-0524B Projected Sales, 2009-2013 (US$ Million)

TriLipix Projected Sales, 2010-2013 (US$ Million)

Aprovel/Avapro Sales 2003A-2012E (US$ Million)

Diovan/Co-Diovan Sales 2003A-2012E (US$ Million)

Cozaar/Hyzaar Sales 2003A-2012E (US$ Million)

Micardis Sales, 2003A-2012E (US$ Million)

Atacand Sales, 2003A-2012E (US$ Million)

Blopress Sales, 2003A-2012E (¥ Billion)

Benicar/Olmetec Sales 2003A-2012E (US$ Million)

Norvasc Sales, 2003A-2012E (US$ Million)

Amlodin Sales, 2003A-2012E (¥ Billion)

Adalat Sales 2003A-2012E (US$ Million)

Zanidip Sales 2003A-2012E (US$ Million)

Vasotec/Vaseretic Sales 2003A-2012E (US$ Million)

Altace/Tritace Sales 2003A-2012E (US$ Million)

Coreg Sales, 2003A-2012E (US$ Million)

Seloken/Toprol-XL Sales 2003A-2012E (US$ Million)

Cardura Sales 2003A-2012E (US$ Million)

Lotrel Sales, 2003A-2012E (US$ Million)

Rasilez/Tekturna Projected Sales, 2007-2012 (US$ Million)

Bystolic Projected Sales, 2008-2013 (US$ Million)

Darusentan Projected Sales, 2009-2012 (US$ Million)

Cleviprex Projected Sales, 2008-2013 (US$ Million)

Ranexa Sales 2006A-2012E (US$ Million)

Procoralan Sales, 2006E-2012E (US$ Million)

Multaq Projected Sales, 2009E-2014E (US$ Million)

Pulzium Projected Sales 2008E-2013E (US$ Million)

Kynapid Projected Sales 2008E-2013E (US$ Million)

Tracleer Sales, 2003A-2012E (US$ Million)

Ventavis Sales, 2005A-2012E (US$ Million)

Revatio Sales, 2005A-2012E (US$ Million)

Thelin Sales, 2006A-2012E (US$ Million)

Letairis/Volibris Projected Sales, 2008-2012 (US$ Million)

Lovenox Sales, 2003A-2012E (US$ Million)

Arixtra Sales, 2004A-2012E (US$ Million)

Plavix/Iscover Sales, 2003A-2012E (US$ Million)

Pradaxa Projected Sales, 2008-2013 (US$ Million)

Prasugrel Projected Sales, 2008-2013 (US$ Million)

Rivaroxaban Projected Sales, 2009-2014 (US$ Million)

Apixaban Projected Sales, 2010-2014 (US$ Million)

Abstract

This market analysis provides:
Unique sales forecasts for key new and current products to 2012

A comprehensive examination of 6 major cardiovascular therapy areas

Critical analyses and competitive ratings for current and upcoming products

6 key cardiovascular therapy areas covered:
Cholesterol and Triglycerides
Hypertension
Coronary Artery Disease
Pulmonary Arterial Hypertension
Atrial Fibrillation

Thrombosis Cardiovascular disease is a global problem. In the developed world, its prevalence is linked to our increasingly unhealthy lifestyle, with risk factors including lack of exercise, overweight and obesity, and smoking. These are also linked to diabetes which increases the risk of developing heart disease.

The global desire for cheaper generic drugs has been putting increasing pressure on the research-based industry, which finds itself having to defend its patents in the courts to ward off generic competition for as long as possible. Legal battles are won and lost on both sides; either way, patents eventually expire and generic competition is inevitable.

But what of the future? Opportunities for new therapies exist in both main and niche markets - the latter being relatively uncompetitive and where there is high unmet clinical need, such as pulmonary arterial hypertension. Among the market leaders, several will lose, or have recently lost, patent protection in major markets over the next few years. The resulting loss in revenue for the research-based industry can be dramatic.

For example, following peak sales of US$5,580 million in 2002, Merck & Co’s Zocor (simvastatin) lost its basic patent protection in Canada and a number of countries in Europe, including the UK and Germany in 2003. Sales subsequently declined in these countries as a result of generic competition.

The US patent on Zocor finally expired on 23rd June 2006, following six months paediatric extension. The FDA approved two generics with 180-days market exclusivity, resulting in a downturn in sales of Zocor to US$2.8 billion for the full year. The entry of multiple generics onto the market from December 2006, however, resulted in a dramatic fall in sales of Zocor in 2007, to US$876 million. The effect of generic simvastatin was not, however, confined to Zocor but rippled through the market, impacting sales of Pfizer’s Lipitor (atorvastatin) in the short term.

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