Dyslipidemia: Opportunities in Cardiovascular Risk Reduction is a 200-page comprehensive and
insightful study of scientific and commercial trends and opportunities in the worldwide
lipid-modulating market, which is poised for transformation with the advent of novel combination
products and biopharmaceuticals. This report is based on extensive primary and secondary
research conducted by Biophoenix' principal executives, Drs Sreten Bogdanovic and Beata
Langlands, who have previously researched and written over 50 in-depth management/market
reports for the healthcare industry.
Buy this Report to:
gain an insight into the performance of statins and other lipid-modulating drugs and
commercial implications of post-marketing clinical trials such as ASTEROID and ENHANCE
1. identify biomarkers and surrogates of atherosclerosis, their potential and limitations in drug
development
2. obtain market forecasts for the dyslipidemia market to 2012 by major market segments and
geographic areas
3. discover why much of the growth in the dyslipidemia market is forecast to come from
non-statin segments, in particular niacins and fibrates
4. be alerted to opportunities presented by the growing challenges of mixed dyslipidemias and
undertreated patient subpopulations
5. identify companies developing novel lipid-modulating drugs (the report mentions over 120
companies)
6. identify the most promising classes of drugs under development, together with their targets
(the report identifies almost 180 marketed and pipeline compounds aimed at 45 unique
molecular targets)
Front Cover
About Biophoenix
About the Authors
Legal Notice
Executive Summary
Chapter 1 Introduction
1.0 Chapter summary
1.1 Dyslipidemia and atherosclerosis
1.2 Atherosclerotic vascular diseases
1.3 Background on lipids and lipoproteins
1.3.1 Lipids
1.3.2 Lipoproteins
1.3.2.1 Apolipoproteins
1.3.3 Association with atherosclerosis
1.3.4 Lipid metabolism
1.4 Atherosclerosis
1.4.1 Overview
1.4.2 Plaque evolution
1.4.2.1 Role of apoB-containing lipoproteins
1.4.3 Vulnerable plaques
1.4.4 Diagnosis and treatment
1.5 Hyperlipidemia
1.6 Atherogenic dyslipidemia
1.7 Lipids, CVD risk and treatment goals
1.7.1 Targeting elevated LDL-C
1.7.2 Targeting elevated triglycerides
1.7.3 Targeting low HDL-C
1.7.4 Targeting the metabolic syndrome
Chapter 2 Biomarkers and surrogates of atherosclerosis
2.0 Chapter summary
2.1 Introduction
2.2 Vascular imaging technologies
2.2.1 Quantitative coronary angiography
2.2.1.1 Brown-Dodge system
2.2.1.2 Edge detection systems
2.2.1.3 Videodensitometric methods
2.2.1.4 Problems and disadvantages
2.2.1.5 Predicting lesion progression
2.2.2 B-Mode ultrasound
2.2.2.1 Principle of B-mode imaging
2.2.2.2 Carotid intimal-medial thickness (CIMT)
2.2.2.3 Risk factors for CIMT and its progression
2.2.2.4 Lipid lowering and CIMT trials
2.2.2.5 Effect of other interventions on CIMT
2.2.3 Intravascular ultrasound (IVUS)
2.2.3.1 Overview of the technique
2.2.3.2 Advantages and disadvantages
2.2.3.3 IVUS trials
2.2.3.4 Intravascular ultrasound elastography
2.2.3.5 Integrated backscatter IVUS
2.2.4 Coronary angioscopy
2.2.5 Optical coherence tomography
2.2.6 Intravascular thermography
2.2.7 Regulatory status of vascular imaging
2.3 Plasma biomarkers
2.3.1 Diagnosis of dyslipidemia
2.3.1.1 Fasting lipid panel tests
2.3.1.2 apoB and apoAI
2.3.1.3 Lp(a)
2.3.1.4 Small dense LDL particles
2.3.2 Emerging biomarkers of risk
2.3.2.1 OxLDL
2.3.2.2 Lp-PLA2
2.3.2.3 CRP
2.3.2.4 Myeloperoxidase
2.3.2.5 Homocysteine
2.3.2.6 PAPP-A
2.3.2.7 CD40L
2.3.2.8 IL-18
2.3.2.9 Other biomarkers
Chapter 3 Improving mainstay therapies
3.0 Chapter summary
3.1 Introduction
3.2 Dietary manipulations
3.2.1 Plant sterols and stanols
3.2.2 Soy-derived isoflavones
3.2.3 Red yeast rice
3.2.4 Essential fatty acids
3.2.5 Omega-3 products
3.2.5.1 Dietary supplements
3.2.5.2 Prescription products on the market
3.2.5.3 Prescription drugs in development
3.3 Statins
3.3.1 Overview
3.3.2 Mode of action
3.3.3 Statins on the market
3.3.3.1 Lovastatin and simvastatin
3.3.3.2 Pravastatin
3.3.3.3 Atorvastatin
3.3.3.4 Fluvastatin
3.3.3.5 Rosuvastatin
3.3.3.6 Other agents and indications
3.3.4 Pharmacogenom+G4ics of statin efficacy
3.4 Cholesterol absorption inhibitors
3.4.1 Ezetimibe
3.4.2 Drugs in development
3.5 Niacin
3.6 Fibrates
3.7 Bile acid sequestrants
3.8 Combination therapies
3.8.1 Statin + ezetimibe
3.8.2 Statin + niacin
3.8.3 Statin + fibrate
3.8.4 Other combination products
3.8.5 Statin-containing "polypills"
Chapter 4 Focus on HDL
4.0 Chapter summary
4.1 HDL-C levels and cardiovascular risk
4.1.1 Prevalence of low HDL-C
4.2 Background on HDL
4.2.1 Structure
4.2.2 Metabolism
4.2.3 Lab measurements
4.2.4 Antiatherogenic activities
4.2.4.1 Cellular cholesterol efflux
4.2.4.2 Antioxidative action
4.2.4.3 Anti-inflammatory activity
4.2.5 HDL in dyslipidemic and inflammatory states
4.3 Current treatments which increase HDL
4.3.1 Niacin
4.3.2 Fibrates
4.3.3 Statins
4.3.4 Combination therapies
4.4 Novel therapies in commercial development
4.4.1 HDL mimetics
4.4.2 ApoAI mimetics
4.4.3 ApoAI-boosting therapies
4.4.4 ABCA1-boosting therapies
4.4.5 CETP-suppressing therapies
4.4.6 Niacin receptor agonists
Chapter 5 Other lipid modulators in development
5.0 Chapter summary
5.1 Introduction
5.2 PPAR agonists
5.2.1 PPAR alpha agonists
5.2.1.1 Agents in development
5.2.2 PPAR gamma agonists
5.2.2.1 TZDs
5.2.2.2 Agents in development
5.2.3 Dual PPAR alpha/gamma agonists
5.2.4 PPAR delta agonists
5.2.5 PPAR pan agonists
5.2.6 Other insulin sensitizers
5.3 Anti-obesity therapies
5.3.1 Obesity and dyslipidemia
5.3.2 Approved therapies
5.3.3 Drugs in development
5.4 Thyroid hormone function agonists
5.5 MTP inhibitors
5.6 Leukotriene antagonists
5.6.1 Targeting Lp-PLA2
5.6.2 Targeting 5-LO and LTA4H
5.7 Succinobucol
5.8 ApoB inhibitors
5.9 Kinase modulators
5.9.1 Targeting MAPK14
5.9.2 Targeting other kinases
5.10 Miscellaneous drugs targeting lipid metabolism
5.11 Miscellaneous drugs targeting inflammation
Chapter 6 Market outlook
6.0 Chapter summary
6.1 Introduction
6.2 The broad spectrum of dyslipidemia
6.3 The dyslipidemia market by therapy
6.3.1 Statins
6.3.1.1 Overview
6.3.1.2 Lipitor
6.3.1.3 Crestor
6.3.1.4 Lescol
6.3.1.5 Livalo
6.3.1.6 Generic statins: lovastatin,
6.3.1.7 Statin-containing "polypills"
6.3.2 Ezetimibe
6.3.3 CETP Inhibitors
6.3.4 Niacin-based Combination Therapy
6.3.5 Fibrates
6.3.6 Bile acid sequestrants
6.3.7 Omega-3 fatty acid derivatives
6.3.8 Other agents
6.4 Forecasts
Chapter 7 Market potential
7.0 Chapter summary
7.1 Introduction
7.2 New therapies
7.2.1 Investing in biopharmaceuticals
7.3 Reaching more patients
7.3.1 Introduction
7.3.2 Maximising statin treatment
7.3.3 Focusing on undertreated populations
7.3.3.1 Targeting hypertensives
7.3.3.2 Targeting women
7.3.3.3 Targeting the elderly
7.3.3.4 Targeting the obese
7.3.3.5 Targeting diabetics
7.3.3.6 Targeting rheumatoid arthritis patients
7.3.3.7 Targeting HIV patients
7.3.3.8 Targeting renal insufficiency patients
7.3.3.9 Targeting schizophrenia patients
7.4 Increasing patient compliance
7.5 Promoting combination therapies
Appendices
Appendix 1 Cholesterol Value Reporting
Appendix 2 Abbreviations and Acronyms
A2.1 Scientific/medical terms
A2.2 Institutions
A2.3 Clinical trials
Appendix 3 Research Methodology
This report examines trends in the dyslipidemia market, which is poised for transformation with the
advent of novel combination products and biopharmaceuticals. The term "dyslipidemia" refers to
abnormal blood lipid values which, individually or in combination, elevate the risk of atherosclerotic
vascular disease. Most lipid-related abormalities can be corrected or at least improved by drug
therapy, and many clinical trials over the past 30 years or so have shown that such treatment
substantially reduces the risk of developing new or worsening disease of the cardiovascular system.
Treatment of dyslipidemia is therefore currently indicated for all patients with cardiovascular disease
(secondary prevention) and for some higher-risk individuals without it (primary prevention). The
report reviews current approaches to treatment, drugs on the market, marketing strategies, lessons
learnt from landmark clinical trials, biomarkers, surrogates of atherosclerosis for drug development,
and pipeline agents. It covers almost 180 agents from over 120 companies aimed at 45 unique
molecular targets. It also derives market forecasts and assesses market potential.
We forecast that, if present trends continue, the dyslipidemia market, dominated by statins, will grow
slowly from $36 billion in 2007 to $42 billion in 2012. As a proportion of the market, statins will fall
from 67% to 44%: most of this decline will occur at the end of the forecast period as Pfizer's Lipitor
(atorvastatin), still the world's top-selling medicine, loses patent protection. Generic statins are
currently worth less than 20% of the audited statin market by sales volume, but their share is
increasing. Much of the growth in the market will come from non-statin segments: niacin, fibrates,
and even prescription omega-3 esters. Important new drug types (e.g. CETP inhibitors, Lp-PLA2
inhibitors, HDL mimetics) are in development, some of which could be introduced towards the end of
the forecast period. We also believe that there are many opportunities for market players to maintain
or increase sales in the meantime, e.g. by means of new drug combinations and improved targeting
of particular patient subgroups.
Current guidelines focus primarily on treating elevated "bad" LDL cholesterol and secondarily on
treating reduced "good" HDL cholesterol and elevated triglycerides. Increasing attention is being
paid to aggressive LDL-C management in high-risk patients. Recent trials such as REVERSAL and
ASTEROID have suggested that atherosclerosis can be halted, or even reversed, in many patients
by such methods. However, the fact remains that therapy focused mainly on LDL-C fails to prevent
most cardiovascular events. There are other lipid parameters that could (and arguably should) be
targeted as well. Emerging lipid and protein biomarkers enable more accurate diagnosis of
dyslipidemia and risk stratification, while vascular imaging technologies enable measurement of
atherosclerotic progression and are potentially useful as surrogate endpoints in clinical trials.
Statins are well established as the primary LDL-lowering intervention. Merck &
Co/Schering-Plough's ezetimibe also primarily lowers LDL-C and is generally used in combination
with statins. We assess the prospects for ezetimibe in the light of the disappointing ENHANCE
study, published early in 2008. Although they are less well tolerated, bile acid sequestrants are
another alternative or adjunct to statins. Niacin is the most effective drug for raising HDL-C, and also
produces some additional degree of LDL lowering when used with statins, but side effects are
common. Fibrates are first choice for lowering triglycerides, despite gastrointestinal side-effects.
There is growing interest in combination therapies, because they can address multiple aspects of
the lipid profile in mixed dyslipidemias, and there are indications that they produce a synergistic
reduction in cardiovascular events. In this situation, fixed-dose combination pills have advantages
and disadvantages. For example they are easier for patients to take, but they make dose
adjustments more difficult. Several such products are on the market, with increasing numbers in
development.
Low HDL-C levels are prevalent and constitute an independent risk factor for CHD. It is increasingly
appreciated that raising HDL-C should not be the only objective, but producing HDL particles with
better functionality is also an important goal. Of the new small molecule drug categories still in the pipeline, CETP inhibitors appear to have the most potential despite the recent well-publicised
withdrawal of torcetrapib following the so-called ILLUMINATE clinical trial. This, however, means
that niacin will remain the most potent HDL-raising agent for some time to come, and has led to a
renewed interest in more tolerable niacin formulations and niacin/statin combinations. Promising
biopharmaceuticals in the pipeline are injectable HDL mimetics which have produced remarkable
effects on the progression and regression of atherosclerosis in preclinical studies. Other lipid
modulators in development include therapies which show promise for the treatment of
hypertriglyceridemia and mixed dyslipidemias and therapies that may attenuate inflammation
associated with atherosclerosis. Since obesity is often associated with lipid abnormalities,
particularly hypertriglyceridemia, treatments for obesity that modulate blood lipids are also of interest
and are reviewed.
MarketsandMarkets.com publishes about 120 report a year across 10 main industries. The reports are exhaustive reports with about 50 micro markets and product segments, about 80 to 100 market data summary tables, 50 short company profiles, market breakdown upto 5 levels, strategic and competitive landscape, patent overview of more than 300 patents.
MarketsandMarkets.com publishes about 120 report a year across 10 main industries. The reports are exhaustive reports with about 50 micro markets and product segments, about 80 to 100 market data summary tables, 50 short company profiles, market breakdown upto 5 levels, strategic and competitive landscape, patent overview of more than 300 patents.