On November 12, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk in adults.
These guidelines represent an important shift from past cholesterol guidelines and are of particular interest to Esperion because we are working to develop ETC-1002. This unique, first-in-class, oral, once-daily investigational small molecule is designed to lower levels of low-density lipoprotein cholesterol (LDL-C) and avoid the side effects associated with existing LDL-C lowering therapies. We are currently evaluating ETC-1002 in a robust Phase 2b clinical program with the goal of developing it for the millions of patients in the United States with hypercholesterolemia who are statin intolerant (i.e., they can’t take statins because of muscle-related side effects) or who have a less-than-anticipated therapeutic response with or without a statin.
We were happy to see in the new guidelines that LDL-cholesterol was positioned as the most important modifiable risk factor for cardiovascular disease. In addition, we were pleased to see that statin intolerance was referenced in the guidelines. Patients who are fully intolerant to statins cannot take a statin at all and the new guidelines acknowledged the need for alternatives for these patients and their physicians.
Although the new guidelines don’t specifically address treatment for statin intolerant patients — our initial target population for ETC-1002 – I believe that the guidelines could benefit Esperion for a number of reasons:
- The guidelines will likely double the number of patients eligible for statin therapy — This could result in a doubling of the number of statin intolerant patients over time.
- The guidelines refocus attention on LDL-C as a key independent modifiable risk factor for ASCVD – LDL-C is the efficacy marker for ETC-1002.
- The guidelines reinforce the importance and primacy of LDL-C lowering – rather than triglycerides and HDL-C — in the management of patients with ASCVD — LDL-C is once again acknowledged as the key lipid marker for treatment/intervention.
- The guidelines elevate the importance of other risk factors – including blood glucose and blood pressure – in managing patients’ CV risk — In our recently completed Phase 2a program, ETC-1002 showed early signs of being able to modulate these risk factors.
- The guidelines highlight the role of LDL-C levels and percent reduction to assess response to therapy and adherence.
- The guidelines acknowledge that some patients are unable to tolerate a less-than-recommended intensity of a statin — a definition that can be applied to statin resistant patients — and that it is important to manage other CV risk factors beyond just LDL-C, including blood glucose and blood pressure. – ETC-1002 has demonstrated beneficial effects on these risk factors in our Phase 2a program.
Thinking about it more broadly and into the future, from my perspective, other key takeaways of the new guidelines are that they:
- Identify – for the first time — four specific patient groups that need to be treated:
- patients with ASCVD
- patients with Type 2 diabetes between the ages of 40 and 75
- patients with LDL-C >190 mg/dL
- patients with >7.5% risk of an event over the next 10 years
- Define the importance of global CV risk assessment in the management of patients with elevated LDL-C to go beyond consideration of LDL-C in isolation.
- Downplay the continued use of ezetimibe and other non-statin LDL-C lowering therapies due to their lack of CVD outcomes data – in the case of ezetimibe more than 10 years after its introduction onto the market – and the risk/reward trade-offs.
- Are “treatment guidelines” — not approval or regulatory guidelines – and it is unclear how the FDA will respond to them; previous guidelines, in contrast, were issued by the NIH through the National Heart, Lung and Blood Institute (NHLBI) and were incorporated into the prescribing information of statins.
There has been discussion around whether CVOT will be needed for regulatory approvals or for reimbursement of potential future LDL-C lowering drugs, including the PCSK9 inhibitor class and our own ETC-1002. While CVOT data may not be needed to gain approval for the statin intolerant patient population, it is more likely necessary for the statin resistant or add-on market, that is, those who have a less-than-anticipated therapeutic response. We have clearly stated that we believe we will need a partner to conduct a CVOT with ETC-1002 to optimize the value of the therapy in this broader patient population – which represents a $6 to $10 billion market opportunity. Payors will want the outcomes data for reimbursement and FDA will want the outcomes data post-approval.
I will be eager to see how physicians, patients and payors alike respond to and adopt the new cholesterol guidelines. In the meantime, we are continuing to evaluate ETC-1002 in our Phase 2b program and will be reporting full results of our Phase 2 ETC-1002-006 clinical study in patients with hypercholesterolemia and a history of statin intolerance next week at the American Heart Association Scientific Sessions on Monday, November 18 (https://cc.readytalk.com/cc/s/registrations/new?cid=fk30ul36zmk3).