Abstract 15986: ETC-1002 Lowered LDL-C and Was Well Tolerated in Hypercholesterolemic Patients With Statin Intolerance
Background: Up to 20% of statin-treated patients are estimated to be intolerant; mainly due to muscle-related adverse events (e.g. muscle pain and/or muscle weakness). ETC-1002 is an oral investigational drug in Phase 2 currently being developed to treat hypercholesterolemia and additional cardiometabolic risk factors through dual mechanisms of action, namely ATP citrate lyase inhibition and AMP kinase activation in liver.
Methods: 56 patients intolerant to statin therapy due to muscle pain and/or muscle weakness received ETC-1002 (n=37) or placebo (PBO; n=19) for 8 weeks. The initial dose of ETC-1002 was 60 mg, force-titrated at 60 mg increments every 2 weeks up to 240 mg. The primary endpoint was percent change from baseline to Week 8 in LDL-C.
Results: ETC-1002 reduced LDL-C by 32% (PBO corrected mean reduction: 29%, p<0.0001; mean baseline LDL-C = 179 mg/dL). ETC-1002 also reduced hsCRP by 42% (p=0.0022 vs. PBO) and non-HDL-C by 25% (p<0.0001 vs. PBO). Of patients not at National Cholesterol Education Panel Adult Treatment Panel-III LDL-C goal at baseline, 21/34 (62%, p<0.0001 vs. PBO) ETC-1002 treated patients reached goal at Week 8 (0/17 PBO patients). In ETC-1002 vs. PBO, rates of muscle-related adverse events (27% vs. 32%) and discontinuations due to muscle-related adverse events (0% vs. 16%) were lower for ETC-1002. No increases in liver function tests ≥3 x upper limit of normal (ULN) or increases of CPK ≥5 x ULN were observed in ETC-1002 treated patients. One case of a single elevation of CPK ≥5 x ULN was observed in a PBO patient.
Conclusion: ETC-1002 lowered LDL-C and hsCRP and was well tolerated. Given the limited therapeutic options, ETC-1002 may offer a viable alternative for the statin intolerant patient with hypercholesterolemia.
- © 2013 by American Heart Association, Inc.