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.