First-in-class cholesterol synthesis inhibitor meets primary endpoint in phase 3 studyMar. 7, 2018 - news
Bempedoic acid has met the primary endpoint in the first pivotal, phase 3 study that evaluated its LDL-C lowering efficacy and safety and tolerability vs. placebo in patients with atherosclerotic cardiovascular disease (ASCVD) or at high risk for ASCVD with hypercholesterolemia inadequately treated with background ezetimibe 10 mg and up to the lowest daily starting dose of a statin.
The 12-week study met its primary endpoint with LDL-C lowering totaling 28% (p<0.001) vs. placebo. The LDL-C lowering for the bempedoic acid group was 23% from baseline, as compared to an LDL-C increase of 5% for the placebo group. Patients treated with bempedoic acid also achieved a significantly greater reduction of 33% in high-sensitivity C-reactive protein (hsCRP), compared to the placebo group which had an increase of 2% (p<0.001). The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined.
With a targeted mechanism of action, bempedoic acid is a first-in-class, complementary, orally available, once-daily ATP Citrate Lyase (ACL) inhibitor that reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. The study was conducted at 90 sites in the U.S., Canada and Europe. A total of 269 patients were randomized 2:1 to receive bempedoic acid or placebo.
In this study, bempedoic acid was observed to be safe and well-tolerated. There were no differences in the occurrence of adverse events (AEs), serious adverse events (SAEs) or muscle-related AEs; and no differences in discontinuations due to AEs or muscle-related AEs between the bempedoic acid group compared to the placebo group. Two patients (1.1%) treated with bempedoic acid had elevations in liver function tests (ALT/AST) of >3ULN, repeated and confirmed. The cumulative number of patients now treated with bempedoic acid in phase 2 clinical trials and in Study 4 totals 919. Of these, six patients (0.6%) had elevations in liver function tests. This rate of elevations in liver function test is consistent with the rate observed in phase 2 clinical trials and with all other previously approved oral LDL-C-lowering therapies, including statins and ezetimibe.
Esperion plans to present full results from this study at an upcoming medical conference and to publish in a major medical journal.