I re-joined Roger at Esperion almost a year ago to help people who are at risk for debilitating and life-threatening heart attacks and strokes because they have elevated levels of LDL-C (the bad cholesterol), but who are unable to take a statin because of myalgia (muscle pain). These patients are considered statin intolerant – and there are an estimated 2 million of them in the United States. While statins are the cornerstone of lipid treatment today and are highly effective at lowering LDL-C, many patients can’t tolerate them due to side effects. Besides myalgia, some patients who take statins suffer memory loss, increased glucose levels and, in rare and extreme cases, muscle breakdown, kidney failure and death.
These patients need a new treatment option. That’s why our team at Esperion is working to develop ETC-1002, a unique, first-in-class, oral, once-daily small molecule designed to lower levels of LDL-C and avoid the side effects associated with existing LDL-C lowering therapies. In October, the first patients were dosed in our initial Phase 2b study, known as ETC-1002-008. This is the first of at least two studies in our Phase 2b program, which is the last step of drug development before we can potentially meet with the FDA for an end-of-phase-2 meeting and then begin pivotal Phase 3 clinical trials. Once we finish our Phase 2b program, we expect to have treated close to 1,000 patients with ETC-1002 – a program comparable in size to those that have been conducted by much larger companies working on LDL-C lowering therapies.
The ETC-1002-008 study is evaluating parallel doses of ETC-1002 over 12 weeks alone or in combination with ezetimibe — the most common therapy used today for statin intolerant patients — to compare the LDL-C lowering efficacy of the two drugs and to characterize tolerability. To participate, patients must have hypercholesterolemia (elevated LDL-C levels) and a history of either statin intolerance (to two or more statins due to muscle-related adverse events) or statin tolerance.
There are several important aspects of the study design that make it unique:
- It is quite large. More than 300 patients are enrolling at up to 75 medical centers in the United States.
- We’re including statin tolerant patients, as well as statin intolerant patients, so we can see how statin intolerant patients respond to ETC-1002 compared with patients who can tolerate a statin — plus add to our safety and tolerability database.
- Rather than using a placebo arm, we’re treating patients with an active control (ezetimibe) because it best represents a real-world treatment setting.
- It is powered to show a 10-percentage-point difference between ETC-1002 and ezetimibe in LDL-C lowering.
The ETC-1002-008 study gives us a great opportunity to learn more about patients with statin intolerance. Additionally, we hope to show, as we did in our ETC-1002-006 study, which also included statin intolerant patients, that ETC-1002 lowers LDL-C and is well tolerated in this difficult-to-treat patient population.
So far, we have completed seven Phase 1 and Phase 2a clinical studies involving more than 300 patients who received ETC-1002. In those studies, ETC-1002 has consistently shown the ability to lower LDL-C by 30 to 40 percent in patients with hypercholesterolemia – at least twice the LDL-C lowering efficacy of ezetimibe. ETC-1002 also lowers levels of high sensitivity C-reactive protein (hsCRP) by up to 40 percent. hsCRP is a key marker of inflammation associated with cardiovascular disease.
At Esperion, we believe that ETC-1002 someday could benefit the 2 million patients with hypercholesterolemia who cannot tolerate a statin. We look forward to reporting top-line results from the ETC-1002-008 study in late 2014. Hopefully, that should give us very useful insights about how we can help these patients.