Combination pill with inhibitors of cholesterol synthesis and absorption met primary endpoint
Positive top-line results from the pivotal Phase 3 bempedoic acid/ezetimibe combination pill study (1002-053) have been announced. This trial was a randomized, double-blind, parallel group study conducted to evaluate the efficacy and safety of the bempedoic acid 180 mg / ezetimibe 10 mg combination pill compared to bempedoic acid, ezetimibe or placebo in high-risk patients with ASCVD and/or heterozygous familial hypercholesterolemia or with multiple risk factors for ASCVD being treated with maximally tolerated statins
Bempedoic acid inhibits ATP Citrate Lyase (ACL) and thereby reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. The combined effects of the complementary mechanisms of action of inhibition of cholesterol synthesis (bempedoic acid) and inhibition of cholesterol absorption (ezetimibe), were evaluated as a non-statin, orally available, once-daily, LDL-C lowering therapy.
The 12-week, pivotal Phase 3 randomized, double-blind, parallel group, multicenter study included 382 high-risk patients taking maximally tolerated statins who required additional LDL-C lowering and met its key efficacy endpoints, including:
- On-treatment analysis LDL-C lowering of 35% for the combination pill at 12 weeks (p<0.001) compared to 3% for placebo, 24% for ezetimibe 10 mg (EZE) and 20% for bempedoic acid 180 mg (BA);
- In the intent to treat analysis, LDL-C lowering was 32% for the combination pill compared to 3% for placebo (p<0.001), 21% for EZE (p<0.001) and 18% for BA (p<0.001);
- Reduction of 34% for the Fixed Dose Combination (FDC) in high-sensitivity C-reactive protein (hsCRP), compared with an increase in placebo of 4% and reductions of 20% for BA and 9% for EZE.
- In a post-hoc analysis of patients considered statin intolerant, the combination pill LDL-C lowering was 43% in the on-treatment analysis compared to a one percent increase for placebo.
In this 12-week study, the bempedoic acid/ezetimibe combo pill was observed to be safe and well-tolerated. The results showed no clinical differences between the FDC, BA, EZE and placebo patient groups in the occurrence of:
- Serious adverse events (SAEs) with 8%, 6%, 9% and 2%, respectively. No SAEs were considered to be related to study medication;
- Discontinuations due to AEs with 7%, 8%, 9%, and 4%, respectively;
- No elevations in liver function tests (ALT/AST) of greater than three times the upper limit of normal, repeated and confirmed were observed.