PLYMOUTH (WWJ) — The pharma startup Esperion Therapeutics Inc. Monday announced full results of a Phase 2 clinical study of its lead drug candidate, called ETC-1002. The drug is intended to reduce high cholesterol levels in patients with a history of intolerance to today’s cholesterol-lowering statin drugs.
Esperion said the study met its primary goal — showing significant reduction of LDL-C, the so-called bad cholesterol, by an average of 32 percent. The drug was also well tolerated by patients, without the side effects of muscle pain and weakness that a significant portion of the population experiences from statin drugs.
The data were presented today in an oral presentation at the 2013 Scientific Sessions of the American Heart Association in Dallas by principal investigator Paul D. Thompson, M.D. Esperion previously announced positive topline results from this study in June.
“To achieve a 32 percent reduction in LDL cholesterol with a non-statin is very impressive and more reduction than any other currently approved lipid lowering agent except the statins,” said Thompson, director of cardiology at Hartford (Conn.) Hospital and professor of medicine at the University of Connecticut. “This drug may have promise for people who have trouble tolerating statins and could be important given that more than 2 million people in the United States are estimated to be statin intolerant. Statin intolerant patients have very few therapeutic options and an oral treatment that significantly lowers LDL-C and is well tolerated could be very useful in this patient population.
Added Tim Mayleben, Esperion president and CEO: “We continue to build on the positive results from this Phase 2 clinical study and recently initiated a large Phase 2b clinical study in statin intolerant and statin tolerant patients. This Phase 2b clinical study will further evaluate the potential of ETC-1002 in statin intolerant patients, a patient population that we believe is underserved by currently available therapies and who remain at elevated risk for cardiovascular disease.”
The study was designed to evaluate the LDL-C lowering efficacy, safety and tolerability of ETC-1002 compared with placebo in patients with high cholesterol and a history of intolerance to two or more statins. The study also assessed the ability of patients with a history of statin intolerance to achieve their NCEP ATP-III LDL-C goal. Study participants were dosed for eight weeks starting at 60 mg for two weeks, followed by 120 mg, 180 mg and 240 mg for two weeks each (or placebo only for eight weeks). A total of 56 patients were evaluated in the study, of whom 37 were randomized to receive ETC-1002 and 19 to receive placebo.
Thirty-one ETC-1002 patients and 15 placebo patients completed eight weeks of treatment. Three patients in the placebo group and none in the ETC-1002 group withdrew from the study for muscle-related reasons (e.g., musculoskeletal pain, muscle fatigue, muscle weakness, myalgia).
Final results showed that ETC-1002 lowered LDL-C by statistically significant 32 percent compared with 3 percent in the placebo group. Approximately two-thirds of patients reached their ATP-III NCEP LDL-C goal. In the ETC-1002 group, high sensitivity C-reactive protein (hsCRP), a recognized marker for inflammation, was significantly reduced after eight weeks by 42 percent (p=0.0022). Levels of ApoB and Non-HDL-C, other important biomarkers, were also significantly reduced.
Overall adverse event rates were comparable between the ETC-1002 and placebo groups, with muscle-related adverse events similar between groups. No serious adverse events were observed among placebo patients; one SAE occurred in the ETC-1002 treatment group that was considered unrelated to the study medication.
According to an academic study of approximately 10,000 current and former statin users published in 2012 in the Journal of Clinical Lipidology, approximately 12 percent of patients on statins discontinue therapy. Approximately 85 percent of patients who discontinued therapy because of side effects cited muscle pain as the primary reason for discontinuing their statin. Based on these data, it is estimated that approximately 6 percent of statin users, or more than 2 million adults in the United States, ceased therapy because of muscle pain and are therefore considered to be statin intolerant. Poor statin adherence can be associated with worse cardiovascular outcomes.
In seven completed Phase 1 and 2 clinical studies, involving more than 300 patients who received ETC-1002, consistent and clinically meaningful reductions in LDL-C cholesterol and high sensitivity C-reactive protein (hsCRP), a key marker of inflammation associated with cardiovascular disease, have been observed. Across all completed clinical studies, ETC-1002 has been well tolerated. To date, one serious adverse event, considered unrelated to ETC-1002, has been observed in 317 patients treated with ETC-1002 at doses of up to 240 mg and up to 12 weeks in duration.
Last month, Esperion initiated ETC-1002-008, the Company’s first Phase 2b clinical study. The study is evaluating parallel doses of ETC-1002 over 12 weeks either alone or in combination with ezetimibe in approximately 322 patients with hypercholesterolemia and a history with or without statin intolerance (to two or more statins due to muscle-related adverse events). The goals of this study are to compare the LDL-C lowering efficacy of ETC-1002 with ezetimibe, a common therapy for statin intolerance, and to characterize tolerability. Top-line results are expected in late 2014.
To listen to a conference call of a speech discussing these results, scheduled for 7:30 p.m. Monday, Nov. 18, call (866) 740-1260 and use the pass code 3906884. A replay of the call will be available at http://www.esperion.com for 90 days after the event.