Hearts & Minds Blog
The Lipid Management Team Reflects on the ESC Congress; the World’s Largest Gathering of Cardiovascular Health ExpertsSeptember 27, 2017
The Lipid Management Team traveled to Barcelona last month to attend the European Society of Cardiology (ESC) Congress, the world’s largest gathering of cardiovascular health experts. To stay on the cutting-edge of the latest cardiovascular breakthroughs impacting patients with hypercholesterolemia around the world, we attended many late-breaking sessions. We also had the opportunity to discuss these recent breakthroughs with experts in the field.
In addition to the overview of the bempedoic acid program presented by Prof. Stephen Nicholls MD, PhD, Professor of Cardiology and Theme Leader at the South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia, there were several additional study results presented at this year’s Congress with relevance to Esperion and our bempedoic acid-based franchise. We are excited to pass along highlights from these sessions, including “soundbites” from experts along with our own takeaways.
“We continue to see residual risk in patients receiving statins. We need better approaches to achieve treatment goals. Bempedoic acid is a novel oral therapy that targets the cholesterol synthesis pathway.” – Prof. Stephen Nicholls, Co-Principal Investigator of the CLEAR Outcomes CVOT
We were gratified that Prof. Nicholls took the podium at ESC in front of a large group of “standing room only” attendees to provide an overview of the bempedoic acid franchise, including details on the mechanism of action; an overview of the Phase 2 results (including the recently announced results of the bempedoic acid / ezetimibe combination plus atorvastatin study); and design of the bempedoic acid global pivotal Phase 3 program and CLEAR Outcomes, the cardiovascular outcomes trial (CVOT).
Prof. Nicholls discussed physicians need for new therapeutic options – especially once-daily, oral therapies – to help their patients achieve their low density lipoprotein cholesterol (LDL-C) goals. To address this need, he highlighted the many benefits of bempedoic acid, used alone or in combination with other oral therapies – including its demonstrated ability to effectively lower LDL-C and high-sensitivity C-reactive protein (hsCRP) – noting that per mg of LDL-C lowering, bempedoic acid should have the same effect on reducing cardiovascular outcomes as statins, ezetimibe and PCSK9s.
The over 400 primarily physician attendees were very engaged. They seemed particularly impressed when Prof. Nicholls presented the 64% reduction in LDL-C seen in our 038 combo + statin study which combined bempedoic acid and ezetimibe with 20 mg of atorvastatin.
We were energized by his presentation, and it was clear that those in attendance were especially interested in how rapidly the bempedoic acid Phase 3 program has advanced along with the recent development of a bempedoic acid / ezetimibe combination pill.
“We now have clear evidence that, in addition to lowering cholesterol, targeting inflammation reduces patients’ risk of cardiovascular disease.” – Paul Ridker, MD, Lead Investigator of the CANTOS study
The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) demonstrated that canakinumab, a cytokine inhibitor, in combination with standard of care following myocardial infarction-therapy, reduces cardiovascular risk in people with a prior heart attack and inflammatory atherosclerosis. The 150 mg dose in the study showed a 37 percent reduction in hsCRP, an important marker of underlying inflammation associated with cardiovascular disease (CVD), without lowering LDL-C, and a 15 percent reduction in risk of nonfatal MI, nonfatal stroke or CV death.
The relevance for Esperion is that bempedoic acid consistently reduces hsCRP. The CANTOS results reinforce the role of inflammation in CVD. CANTOS showed that reducing inflammation, as reflected by a lowering of hsCRP levels, clearly reduces cardiovascular risk. While we have powered the CLEAR CVOT solely based on LDL-C reduction, it is possible that reductions in hsCRP by bempedoic acid could potentially contribute to additional CVD risk reduction in this large outcomes study. We are measuring the effect of bempedoic acid on hsCRP as a pre-specified secondary endpoint in our Phase 3 clinical studies and in our CLEAR CVOT.
CANTOS has shown that in patients with cardiovascular disease and well-treated LDL-C who also have elevated hsCRP, the addition of a therapy that targets inflammation alone can reduce the risk of cardiovascular disease.
“The REVEAL trial has shown for the first time that adding a CETP inhibitor to intensive statin therapy reduces the incidence of cardiovascular events in high-risk patients.” – Martin Landray, Co–Lead Investigator of the REVEAL study
Similarly, the data from the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) study, as presented at ESC, further validates the LDL-C lowering thesis by demonstrating a statistically significant reduction in MACE in the 30,449 patients with ASCVD studied.
Why is this relevant to Esperion? Positive results from REVEAL demonstrate once again that lowering LDL-C reduces CVD risk. This has now been shown with three non-statin agents (ezetimibe, evolocumab and now anacetrapib) making us even more confident that bempedoic acid, which lowers LDL-C and apoB concordantly, will likewise reduce CV risk. We’re confident that LDL-C lowering will remain an accepted and important surrogate for CVD risk reduction – as it has been for the past 40 years.
Importantly, the results of REVEAL provided further validation of what we at Esperion now call the “LDL-C thesis.” The interest in REVEAL reaffirmed the need for new, oral, complementary non-statin LDL-C lowering therapies in the cardiology community.
Our time in Barcelona reinforced that we are truly approaching what will be the most eventful and transformative year ever for Esperion. We enjoyed learning from, and interacting with, leaders in the field of Lipid Metabolism and Cardiovascular Disease. The results presented at the ESC meeting in Barcelona were validating to our approach addressing the needs of the millions of patients who are living with elevated LDL-C despite maximally tolerated statin therapy.
The next major scientific cardiovascular disease-focused meeting, the American Heart Association (AHA) Scientific Sessions 2017, will be held November 11-15 in Anaheim, California. We will be attending this event in person and will be sure to share LDL-C lowering highlights from that meeting as well.