On Wednesday, Esperion Therapeutics (NASDAQ:ESPR) reported data from the first of five trials evaluating its cholesterol-lowering drug, bempedoic acid. The results show bempedoic acid successfully lowered bad cholesterol levels; however, that wasn't enough to overcome concerns associated with its safety. Should investors be worried?

Controlling cholesterol

Millions of Americans have high bad cholesterol levels, and since elevated LDL-C can signal an increased risk of heart disease, drugs that are prescribed to control cholesterol are among the most commonly prescribed medicines in the United States.

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About one in five Americans between ages 40 to 75 take statins in a bid to keep their cholesterol in check, yet many patients still fail to hit their bad cholesterol targets. Despite the widespread use of megablockbuster therapies, including generic Lipitor and Zetia, an estimated 600,000 Americans still die every year from heart disease, according to the Centers for Disease Control and Prevention.

In hopes of helping more patients control their cholesterol, Amgen Inc. (NASDAQ:AMGN) and Regeneron Pharmaceuticals (NASDAQ:REGN) launched new drugs -- Repatha and Praluent -- in 2015 that increase the number of bad cholesterol receptors in the liver by inhibiting the PCSK9 gene responsible for breaking down these receptors. In trials, these PCSK9 drugs lowered bad cholesterol by an additional 60% when added to statin therapy.

Although PCSK9 drugs are effective, they're also expensive specialty biologics that aren't suitable for widespread use. As a result, there's still an important need for additional cholesterol-lowering drugs that can be used by the masses.

Delivering the goods

Unlike statins that curb cholesterol by inhibiting the HMG-CoA reductase enzyme, bempedoic acid inhibits ATP-Citrate Lyase, which is upstream of the HMG-CoA reductase enzyme. Because bempedoic acid has a different target than statins, Esperion Therapeutics hopes to win approval for its use as a monotherapy in statin-intolerant patients, and for use alongside statins in patients who are struggling to hit their cholesterol goals.

In mid-stage trials, bempedoic acid lowered bad cholesterol by roughly 20% when added to statins, and adding it to Zetia resulted in an approximately 50% LDL-C improvement and a greater than 25% improvement in C-reactive protein, a biomarker that's associated with clogging arteries. 

The phase 3 data reported on Wednesday seems to confirm bempedoic's efficacy. Specifically, adding bempedoic acid to Zetia in statin-intolerant patients lowered bad cholesterol by an additional 23%. Alternatively, patients in the placebo arm of the study saw their bad cholesterol levels increase 5%. Patients receiving bempedoic acid also had a 33% reduction in C-reactive protein.

What's the problem?

Despite those results, Esperion Therapeutics shares traded down by as much as 10% early on Wednesday following the news. The culprit may be concern over elevated liver enzymes. In the trial, two patients, or 1.1% of participants, had liver enzymes levels in their blood that were greater than three times the upper limit of normal. 

The risk of liver damage shouldn't be ignored, but the findings ought to be put in context. Elevated levels of liver enzymes are found in 1% to 3% of patients taking statins, and large-scale studies of Lipitor, the most common statin, show that elevated enzymes above 3 times the upper limit of normal occur in 0.7% of patients

So far, that's about what we've seen across the entirety of the bempedoic acid patient population, too. Specifically, elevated enzyme levels above 3 times the upper limit of normal have occurred in 0.65% of the 919 patients particpating in phase 2 trials and phase 3 trials that have been reported so far. 

Since Esperion Therapeutics has been guiding for investors to expect safety results to "vary from study to study," investors might not want to draw too many conclusions from the 1.1% rate in this relatively small, 269 patient study.

More data on tap

Investors' attention now shifts to the remaining four phase 3 trials that are expected to read out data this year. Those trials include:

  • Two pivotal studies (studies 1 and 2) in patients with atherosclerotic cardiovascular disease (ASCVD) on maximally tolerated statin therapy, with top-line results expected in early May and September 2018, respectively.
  • One pivotal study (study 3) in statin-intolerant patients with ASCVD, or at a high risk for ASCVD, with top-line results expected in May 2018.
  • One pivotal study evaluating a bempedoic acid/Zetia combination pill in 350 patients with ASCVD, or at high risk for ASCVD, on maximally tolerated statin therapy, with top-line results expected in August 2018.

Overall, bempedoic acid's phase 3 trials are enrolling 4,000 patients, so it's too early to say that safety results from this one trial pose a risk to its approval. Assuming the drug's efficacy holds up and liver tests across the entire body of studies wind up being similar to Lipitor, I think bempedoic acid has the makings of a 9-figure drug. That said, you can bet everyone will be looking very closely at safety results when data is released from its next study in May.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.