Esperion Therapeutics, Inc. (Nasdaq: ESPR), a clinical-stage biopharmaceutical company, today announced positive top-line results from a Phase 2a study of ETC-1002 when added to statin therapy in patients with elevated levels of low density lipoprotein cholesterol (LDL-C or "bad cholesterol"). The study demonstrated that oral, once-daily ETC-1002 achieved incremental LDL-C lowering of 22 percent at eight weeks, compared with 0 percent in the placebo group, when added to 10 mg of atorvastatin (p<0.0001). ETC-1002 was well tolerated over eight weeks of treatment when added to a statin and no serious adverse events (SAEs) were reported.
“We are now in a position to build on these positive results with a robust, parallel-dose design Phase 2b study to establish further the potential of ETC-1002 to provide incremental LDL-C lowering for patients already taking a statin and not at their LDL-C goal.”
"Since a 10 mg dose of atorvastatin provides 30 to 35 percent LDL-C lowering, the addition of ETC-1002 could potentially provide LDL-C lowering of greater than 55 percent with an oral dosing regimen. While statin therapy remains the standard of care for high cholesterol, it is estimated that 11 million Americans are still unable to reach their LDL-C treatment goals despite taking a statin," said Roger S. Newton, PhD, FAHA, executive chairman and chief scientific officer of Esperion.
"This study answered important questions about the safety, tolerability and efficacy of ETC-1002 as an add-on to statin therapy," said Tim M. Mayleben, president and chief executive officer of Esperion. "We are now in a position to build on these positive results with a robust, parallel-dose design Phase 2b study to establish further the potential of ETC-1002 to provide incremental LDL-C lowering for patients already taking a statin and not at their LDL-C goal."
ETC-1002-007 Design
The ETC-1002-007 study was a randomized, double-blind, placebo-controlled, multicenter, Phase 2a study to evaluate the safety and tolerability of ETC-1002 when added to 10 mg of atorvastatin and assess the effect of ETC-1002 on the pharmacokinetics of atorvastatin in patients with hypercholesterolemia. Secondary objectives were to assess the effect of ETC-1002 on LDL-C and other cardiometabolic risk factors when added to atorvastatin. Fifty-eight patients with hypercholesterolemia were washed out of any lipid regulating therapies prior to a four week run-in period on 10 mg atorvastatin (mean baseline LDL-C levels of 106 mg/dL at week 0 prior to randomization). Forty-two of these patients were randomized to receive ETC-1002 plus 10 mg atorvastatin. All ETC-1002 treated patients received escalating daily doses of 60, 120, 180 and 240 mg ETC-1002, each over a two week period, for a total of eight weeks. Sixteen patients received placebo plus 10 mg atorvastatin also for eight weeks.
ETC-1002-007 Results
Adverse events (AEs) were generally mild and no SAEs were observed in either the ETC-1002 or placebo groups. Thirty-nine out of 42 ETC-1002 treated patients (93%) and 14 out of 16 placebo treated patients (88%) completed eight weeks of treatment. Two patients in the ETC-1002 plus atorvastatin group withdrew from the study due to AEs. One patient had an elevated liver enzyme laboratory finding that resolved when ETC-1002 and atorvastatin were discontinued. The other patient's AE was unrelated to ETC-1002. There was a weak pharmacokinetic interaction of ETC-1002 with atorvastatin. ETC-1002 treated patients achieved incremental LDL-C lowering of 22 percent at eight weeks, compared with 0 percent in the placebo group, when added to 10 mg of atorvastatin (p<0.0001).
Limitations of Statin Therapy
Statins are the standard of care for LDL-C lowering treatment today and are highly effective at lowering LDL-C. The benefits of using statins to lower LDL-C levels and improve cardiovascular outcomes are well documented. However, a significant number of patients are unable to tolerate statins due to the side effects, primarily muscle pain or weakness. Based on data from the USAGE survey, as published in the Journal of Clinical Lipidology in 2012, we estimate that more than 2 million adults in the U.S. are statin intolerant. Additionally, many patients are unable to reach their LDL-C goal on statin therapy alone. The Centers for Disease Control and Prevention estimates that there are approximately 11 million patients in the U.S. who are currently on lipid-lowering therapy but are unable to achieve their LDL-C treatment goal. These patients remain at elevated risk for cardiovascular disease.
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