If you're looking to buy some stocks that hinge on the development of new cholesterol drugs, you're probably on to something big. Roughly one-third of American adults have high levels of "bad" cholesterol, but an estimated 38 million of them aren't taking any cholesterol-lowering drugs.

General laziness keeps plenty of patients from seeking treatment in the first place, but muscle pain and weakness is another big reason around half of all patients that begin treatment with statins stop taking them within a year. In addition to several million patients who can't tolerate statins, another 9 million take all the statins they can handle but still can't keep their cholesterol levels in check.

Blister pack full of dollar signs instead of pills.

Image source: Getty Images.

Clearly, there's s lot of demand for new cholesterol drugs. Here's why Esperion Therapeutics Inc. (NASDAQ:ESPR)Akcea Therapeutics Inc. (NASDAQ:AKCA), and The Medicines Company (NASDAQ:MDCO) are the stocks best-positioned to soar by addressing one of the world's largest unmet medical needs right now.

1. Esperion Therapeutics Inc.: An important distinction

Lipitor was a $13 billion-a-year tablet before generic competition hammered its sales figures into the dirt. This company's lead candidate, bempedoic acid, is similar to Lipitor with a very important difference: Esperion's candidate remains inactive until it's in the liver, which explains why it isn't associated with the sort of muscle tissue-related side effects that cause millions of patients to quit their statin treatments.

Esperion can point to heaps of successful mid-stage clinical studies that show bempedoic acid effectively lowers cholesterol for patients with severe, genetically driven cases of hypercholesterolemia, everyday patients that just can't handle statins, and practically every group in between. That gives bempedoic acid a huge potential patient population that could drive sales of the drug well over $1 billion each year. First, however, Esperion needs to convince the Food and Drug Administration (FDA) to approve bempedoic acid to treat a wide range of indications.

Esperion thinks it will submit new drug applications for its candidate in the first quarter of 2019. In the meantime, investors will want to keep their eyes peeled for data from a 2,230 patient long-term safety study expected in the second quarter of 2018. I'm fairly confident bempedoic acid will reach pharmacy shelves. In order to fly off those shelves, though, Esperion needs to show its drug is easy to tolerate.

Doctor consulting with a patient.

Image source: Getty Images.

2. Akcea Therapeutics Inc.: Beyond just cholesterol

By the time Esperion's ready to submit its first new drug application, Akcea Therapeutics could already have begun generating sales from its first product. This company was spun off from Ionis Pharmaceuticals in mid-2017, shortly before submitting applications for volanesorsen as a treatment for patients with familial chylomicronemia syndrome (FCS).

To be fair, FCS is characterized by high levels of circulating triglycerides, not their cholesterol cousins. FCS patients often experience bouts of extreme abdominal pain and potentially fatal acute pancreatitis. During a clinical trial supporting new drug applications under review, the average patient given volanesorsen saw their triglyceride count fall 77% after three months versus an 18% increase among those in the placebo group.

Akcea's expects the Food and Drug Administration (FDA) to issue an approval decision around the end of August 2018, although it could come sooner. Five of 113 patients in the study discontinued treatment due to platelet count reductions. Given the severe nature of the rare diseases at which Akcea is aiming volanesorsen, platelet issues probably won't prevent regulators from approving the drug for patients who currently lack effective treatment options.

Peak estimates vary widely, but a successful volanesorsen launch would probably lead to around $200 million in annual sales for Akcea. That would go a long way to fund development of AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, and AKCEA-APOCIII-LRx. All three of these programs are in mid-stage clinical trials for the treatment of rare lipid-based disorders that lack effective treatment options.

3. The Medicines Company: The next next-generation cholesterol drug

Next-generation drugs that boost the liver's ability to absorb cholesterol by blocking the PCSK9 enzyme from doing its job are highly effective, but their commercial launches have been disappointing. Partners Sanofi and Regeneron thought annual Praluent sales would quickly top several billion when the injectable cholesterol-lowering therapy launched in 2015. When the pair last reported earnings, Praluent had only achieved a $196 million annualized run rate.

The Medicines Company thinks it can top Praluent's performance with inclisiran, an experimental drug that stops PCSK9 from being produced in the first place. The Medicines Company licensed inclisiran from Alnylam (NASDAQ:ALNY) for just $25 million upfront back in 2013, which now looks like the deal of the century.

Alnylam remains eligible for milestone payments and double-digit royalties, but The Medicines Company still stands to realize an enormous return on its initial investment. Praluent is available as a monthly injection. During the Orion-1 trial, inclisiran was able to reduce patients' cholesterol by 51% during a six-month period between doses. 

Although the general public accepts that high cholesterol leads to heart disease, the insurers and governments that pay for cholesterol-lowering drugs want to know they'll save money over the long run. We'll get a better idea of whether or not the cholesterol reductions inclisiran produces actually lead to fewer heart attacks when the company reports data from the 382-patient Orion-3 trial.

The study, which pits inclisiran against Repatha, a PCSK9 blocker from Amgen, passed a recent interim analysis and should read out sometime in 2019. Inclisiran is a relatively easy drug to manufacture compared to its potential PCSK9 rivals. This means The Medicines Company can probably undercut its PCSK9 rivals on price, while maintaining healthy profit margins. If Orion-3 results confirm a long-term efficacy edge for inclisiran without major safety issues, the drug could eventually rack up several billion in annual sales at its peak.

Cory Renauer has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends Alnylam Pharmaceuticals and Ionis Pharmaceuticals. The Motley Fool has a disclosure policy.