Source: Flickr via user Sandra-Cohen Rose.

A new generation of potent cholesterol-lowering drugs, called PCSK9 inhibitors, may be close at hand. This week, the Food and Drug Administration will hold advisory-committee hearings for the injected experimental drugs Reptha (evolucumab) from Amgen (NASDAQ:AMGN) and Praulent (alirocumab) from Sanofi (NASDAQ:SNY) and Regeneron Pharmaceuticals (NASDAQ:REGN)

By blocking the production of proprotein convertase subtilisin kexin type 9, or PCSK9, these drugs dramatically enhance the liver's ability to break down "bad" cholesterol, known as LDL-C. According to the clinical trial data, Praulent and Reptha reduced circulating LDL-C levels by between 39% to 61%, when used as either a monotherapy or in combo with a statin. That puts them on par with so-called "high-intensity" statins such as Pfizer's (NYSE:PFE) Lipitor (atorvastatin) and AstraZeneca's Crestor (rosuvastatin).

Although Wall Street has long been enamored with this new class of cholesterol drugs in light of the fact that they are each expected to generate nearly $3 billion in peak sales, the FDA may not share the Street's enthusiasm. Here's why. 

PCSK9 inhibitors may not be a better mousetrap 
While head-to-head studies pitting PCSK9 inhibitors against a high-intensity statin have yet to be performed, their seemingly similar efficacy profiles may prove problematic for these big pharma and biotech companies during this week's advisory committee hearings. 

Here are the key issues: Crestor and Lipitor will both be widely available as cheap generics next year, they are known to reduce the likelihood of adverse cardiovascular events in certain patient populations with extremely high LDL-C levels, and they come in pill form. These new PCSK9 inhibitors, on the other hand, will be expensive name brands, their effects on the cardiovascular system (good or bad) won't be understood until additional ongoing late-stage trials are completed, and they are injected. 

Source: Flickr via user Steven Damron.

And that's why Amgen and Sanofi/Regeneron couched the regulatory reviews of their respective drugs in terms of a niche market -- namely, patients who are "statin intolerant." The problem is that no one, including these companies, really knows who these patients are in the real world. 

According to the FDA briefing documents for Reptha, for example, the agency openly questioned what the phrase "statin intolerance" means. After all, some patients who simply refuse to take statins are being labeled as "intolerant," even though there's no underlying medical reason for their refusal.

So the agency is asking reviewers this week to base their decisions largely on one question:

For what population(s), if any, does the LDL-C-lowering benefit of these PCSK9 inhibitors exceed their risks to support approval?

Without any direct link to a cardiovascular benefit at this point, reviewers may be hard pressed to find any population where these novel cholesterol-lowering drugs are worth the risk. 

What's next?
Based on what we've seen so far from the FDA, the agency apparently feels comfortable with the LDL-C lowering abilities, and perhaps the safety profiles, of these two drugs. So, normally, such a situation would lead to a regulatory approval. Investors, though, shouldn't be shocked if the agency ends up issuing Complete Response Letters following these initial reviews, centering on the need for more insight into any potential cardiovascular benefits produced by this novel class of drugs as a whole. That would push their next reviews out until the 2017 to 2018 timeframe, when their ongoing cardiovascular outcomes trials wrap up.

Put simply, you may not want to be buying these stocks right now based on the hope that these blockbusters-in-waiting will drive revenues significantly higher in the short term.