Third PCSK9 Inhibitor for Lowering Cholesterol Moves into Phase III Trials

New study answers questions about the safety of bempedoic acid.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream. Regeneron/Sanofi and Amgen launched two new PCSK9 inhibitors as LDL cholesterol–lowering drugs in 2018 –– Praluent (alirocumab) and Repatha (evolocumab), respectively. Originals list prices were set at more $14,000 annually, but both companies have since or will soon drop those prices to between $4500 and $8000.

Esperion Therapeutics is developing a third PCSK9 inhibitor that it plans to price below $4000/year and consequently hopes will claim significant market share. However, the company has been plagued by questions about bempedoic acid’s safety. In May 2018, an earlier clinical was found to show an imbalance in patient deaths in the treatment and placebo arms. The imbalance was not judged to relate to the drug, but it created doubts about other results. 

Recently, Esperion announced that it has data from a fifth phase III study that answer these questions. In “Study 2,” serious adverse events occurred at similar rates in the placebo and drug arms, and no fatal events were linked to the drug. In fact, patients receiving bempedoic acid were less likely to have a major adverse heart event compared with those on placebo.

Patients receiving the drug in combination with statin therapy saw a significant 17% reduction in LDL levels compared with treatment with statins alone. The company is also developing a fixed-dose combination with ezetimibe, which has shown LDL lowering of 32% compared with statins.

Esperion is developing bempedoic acid for patients that cannot achieve low enough cholesterol levels when taking maximum doses of statin therapies or generic Zetia (ezetimibe). The company believes that its lower-cost option, in combination with statins or ezetimibe, can provide sufficient LDL lowering for most patients and thus will be an attractive option compared with more expensive options. 

With the positive results of Study 2, Esperion is expected to submit a new drug application to the U.S. Food and Drug Administration shortly with hopes of receiving approval in 2019.

Cynthia A. Challener, Ph.D.

Dr. Challener is an established industry editor and technical writing expert in the areas of chemistry and pharmaceuticals. She writes for various corporations and associations, as well as marketing agencies and research organizations, including That’s Nice and Nice Insight.