Hearts & Minds Blog

Going with Your Gut

Roger Newton, PhD, FAHA

Executive Chairman and Chief Scientific Officer

Sometimes in science, you have to go with your gut. Years ago, my gut instinct told me that a drug I was working on would be successful, even though it was still early in development and several effective competitors were already on the market. I believed in this drug so much that I begged the company multiple times not to discontinue the program, and pleaded with them for the necessary funds to continue development. I wrote memos to the business people at Warner-Lambert saying that if they licensed this drug away, they would regret it for the rest of their lives.

I put my credibility on the line–and I turned out to be right. The drug that I worked so hard to save eventually became Lipitor (atorvastatin calcium)–the world’s best-selling statin and best-selling drug, which has helped millions of people lower their low density lipoprotein cholesterol (LDL-C) levels.

I’m not the kind of person who is happy to sit back and relax. There are always new medical problems to solve, especially with cardiovascular disease. That’s why I’m back leading a team at the new Esperion to develop a new therapy for the millions of people with elevated LDL-C (also known as hypercholesterolemia) who aren’t able to tolerate statins.

Our efforts are focused on a compound called ETC-1002, which is a first-in-class therapy designed to significantly reduce levels of high LDL-C and improve other cardiometabolic risk factors without many of the side effects associated with statin use. ETC-1002 works by inhibiting one enzyme and activating another that the body uses to synthesize cholesterol in the liver. By influencing these enzymes, ETC-1002 has the potential to not only lower LDL-C, but also reduce blood pressure, blood glucose, inflammation and weight gain. ETC-1002 also doesn’t appear to accumulate in the blood and muscles, as statins can in some people, causing them pain and weakness.

Having a promising therapy in development doesn’t mean that you’ll be successful in the marketplace. At times I feel like Sisyphus, the mythological Greek character who is forced to repeatedly push a boulder up a hill, only to have it roll down to the bottom again. Just as I had to fight to keep Lipitor on track, our team has had to overcome several hurdles to push forward the development of ETC-1002.

The biggest challenge was getting back the rights to ETC-1002 from Pfizer, which acquired the first Esperion in 2004 in part because of the promise our HDL therapies had shown in early clinical studies. However, a few years later, Pfizer decided to shift its research and development efforts away from cardiovascular disease, and, as a result, Esperion’s programs were no longer relevant.

In 2007, I made the decision to try to re-start Esperion–and to re-acquire the Esperion name and, most importantly, the rights to ETC-1002 and another program. I believed very strongly in the potential of ETC-1002 even though it was still very early in development. After nearly a year of negotiations, I successfully acquired ETC-1002 and the Esperion name, and several of the original Esperion colleagues are back working with me. I can’t express how excited I am to be working with them and the rest of the team to develop a therapy that could potentially help millions of people lower their LDL-C and reduce their risk of cardiovascular disease–still the nation’s (and the world’s) number one killer!

Right now, Esperion is the only company in mid-stage clinical development with a once-daily, oral small molecule to lower LDL-C levels in individuals who can’t tolerate statins. While I can’t predict the future, my gut–and our clinical research to date–tells me that ETC-1002 will be successful in lowering LDL-C in patients with hypercholesterolemia–not only for those who can’t tolerate statins, but also for those who are considered to be statin resistant. These are individuals who need additional LDL-C lowering to achieve their LDL-C goal despite already being on a statin.

What we are doing isn’t easy. While I could have retired several years ago, I like challenges, and more importantly, I like to finish what I have started. I also love what I do and have spent my entire career working to help save lives. I’m not ready to give up on that goal. We still have a lot of work to do. That boulder isn’t over the hill just yet!