The link between high low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) risk is well established, as is, the evidence showing that agents that reduce LDL-C can prevent CV events. The most well know of such agents are the statins, but not every patient can, and some do not want to, take statins. Moreover, for some patients, statins are not effective enough. However, few non-statin therapies have been shown to reduce the risk of CV events. As a result, there are a lot of people with high cholesterol and high CV risk out there.

One novel drug class that could address this important unmet need is the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. These drugs are the it drugs for 2015. Rarely has a class of emerging therapies caused such excitement amongst experts. The PCSK9 inhibitors can reduce LDL-C by more than 50% on top of statins, and thus far, they appear to have a clean safety profile, giving lipid specialists great encouragement.

Three PCSK9 inhibitors are in advanced stages of development: Amgen's evolocumab, Sanofi/Regeneron's alirocumab (Praluent), and Pfizer's bococizumab. Most thought leaders are unable to differentiate them at this stage; efficacy, safety, and delivery attributes all appear similar. It is unlikely that these drugs will be approved for general hypercholesterolemia initially. What is more likely is that the PCSK9 inhibitors will be approved for niche populations, such as familial hypercholesterolemia and possibly patients with statin intolerance. However, evolocumab and alirocumab are already currently under regulatory review and expected to be approved and launched in 2015, whereas bococizumab may not be on the market until 2017. Only when positive CVOT data are demonstrated, and this is not expected until 2018 at the earliest, will they received broader labels.

At first glance you would think evolocumab and alirocumab are in the box seat for achieving dominance of the market. How could bococizumab compete with agents that will have built up 2 years, worth of confidence amongst physicians.

Well, think about how the statins entered the market. Which was the first statin to launch Merck's Mevacor (lovastatin), now one of the lesser prescribed statins. Which was the fifth statin to hit the market. Pfizer's Lipitor (atorvastatin). That drug did okay, didn't it. When Lipitor was launched, there were already three blockbuster statins, but some strong data and an excellent marketing campaign made Lipitor the best-selling drug of all time. Pfizer could do it again, or at the very least close the gap on evolocumab and alirocumab.

How, Firstly, only a small fraction of physicians manage the niche populations who are likely to receive the PCSK9 inhibitors initially. Secondly, these agents are expected to be expensive, which will also limit their use. Thirdly, the CVOT trials for all of the PCSK9 inhibitors are expected to complete within a 6-month window; as these data are likely to facilitate any label expansion, the CVOT results are likely to be much more important for determining market impact and drug uptake. Fourthly, the CVOTs for bococizumab include a much broader range of patients than its competitors, which might sway physicians to turn to bococizumab once they weigh up the CVOT results for all agents. Finally, Pfizer has a wealth of experience and marketing power that can be mobilized to provide medical education about bococizumab and inspire confidence in prescribers.

So, although bococizumab may seem to be at a disadvantage in the PCSK9 inhibitor race, we have already seen Pfizer turn a late-to-market drug into a blockbuster, and they could well do it again.

Tim Blackstock, M.B. Ch.B., M.Phil., is a Business Insights Analyst in the Cardiovascular, Metabolic, and Renal Disorders team at Decision Resources Group.

In-depth analysis of dyslipidemia, with accompanying epidemiology driven sales forecast models, are presented in Decision Resources Group's Dyslipidemia Pharmacor, available here.

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