Results from ETC-1002-009, a phase 2b study evaluating the efficacy and safety of ETC-1002 ( Bempedoic acid ) compared with placebo in patients with hypercholesterolemia on stable statin therapy, were presented.
Results showed the 12-week study met its primary endpoint of greater LDL-cholesterol lowering from baseline with ETC-1002 compared with placebo.
ETC-1002-treated patients achieved 17 and 24% incremental reductions in LDL-cholesterol at doses of 120 mg and 180 mg, respectively, compared with patients on stable statin therapy alone.
These reductions were significantly different from placebo ( p=0.0055 and p less than 0.0001, respectively ), occurred within the first two weeks of initiating therapy, and continued throughout the treatment period.
Consistent with prior studies, ETC-1002 has demonstrated reductions of up to 30% in high-sensitivity C-reactive protein ( hsCRP ), an important marker of inflammation in coronary disease.
Many patients with hypercholesterolemia still have elevated LDL-cholesterol levels despite being on statin therapy, and are often unable to tolerate the statin doses necessary to achieve optimal LDL-cholesterol lowering.
ETC-1002 produced no increases in muscle-related adverse events. There was one reported serious adverse event in the ETC-1002 treatment arms, which was not drug-related.
Discontinuation rates were low overall and lower in ETC-1002-treated patients than those seen in placebo, and were not muscle-related.
The 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel group ETC-1002-009 trial evaluated the efficacy and safety of ETC-1002 versus placebo when added to stable statin therapy in patients with hypercholesterolemia.
A total of 134 patients with hypercholesterolemia were washed out of any lipid-regulating therapies, except Atorvastatin, Simvastatin, Rosuvastatin, or Pravastatin.
Forty-three ( one patient was randomized but did not receive study drug ) patients received ETC-1002 120 mg; 45 patients received ETC-1002 180 mg; 45 patients received placebo.
ETC-1002 is a novel, first-in-class, orally available, once-daily LDL-C lowering small molecule designed to lower levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies.
ETC-1002 has a unique dual mechanism of action that has the potential to regulate both lipid and carbohydrate metabolism.
ETC-1002 appears to work by inhibiting ATP citrate lyase ( ACL ), a key enzyme in the cholesterol biosynthetic pathway, and activating a complementary enzyme, 5′-adenosine monophosphate-activated protein kinase ( AMPK ). Both enzymes are known to play significant roles in the synthesis of cholesterol and glucose in the liver.
By inhibiting cholesterol synthesis in the liver, ETC-1002 causes the liver to take up LDL particles from the blood, which reduces LDL-C levels. ( Xagena )
Source: Esperion Therapeutics, 2015