EC approves cholesterol biosynthesis inhibitor, alone and in combination with ezetimibe
The European Commission has announced the approval of the first-in-class ATP Citrate Lyase (ACL) inhibitor bempedoic acid and the combination tablet of bempedoic acid and ezetimibe for treatment of hypercholesterolemia and dyslipidemia in Europe. Bempedoic acid lowers LDL-c by inhibition of cholesterol synthesis in the liver. The combination pill lowers LDL-c by complementary mechanisms: inhibition of cholesterol synthesis in the liver and absorption in the intestine. Both are approved for use in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet.
Professor Kausik K. Ray, Professor of Public Health at the School of Public Health, Imperial College London and a Consultant Cardiologist and member of the Phase 3 steering committee for Esperion said about the combination tablet of bempedoic acid and ezetimibe: “This daily medicine will be beneficial for those that need additional lowering of bad cholesterol on top of statins but will also provide a convenient alternative for a significant number of people who cannot tolerate statins. These patients now have an efficacious oral option to lower their bad cholesterol. A single combination pill aides adherence, a critical factor to maintain long-term reductions in bad cholesterol.”
These approvals are supported by data from a global pivotal phase 3 LDL-c lowering program and the phase 3 fixed combination tablet LDL-c lowering program, in addition to the existing ezetimibe safety profile. Bempedoic acid resulted in additional lowering of LDL-c by 28% compared to placebo. The combination tablet lowered LDL-c by a mean of 38% compared to placebo on a background of maximally tolerated statin therapy. In addition, non-HDL-c, apoB and total cholesterol were reduced with bempedoic acid and the combination pill. The label of both bempedoic acid and the combination pill highlights that in patients with diabetes (n=1134) levels of HbA1c were lowered compared to placebo (on average 0.2%).
Both were well tolerated in clinical studies. Most commonly reported adverse reactions were hyperuricemia, pain in extremities and anemia with bempedoic acid and hyperuricemia and constipation with the combination pill. Majority of adverse reactions were mild to moderate and were seen in a similar rate in the studied drug group and placebo group. More patients on bempedoic acid discontinued treatment compared to the placebo group in pooled placebo-controlled clinical trials with bempedoic acid, but this finding was not significant.
The CLEAR CV outcomes trial studies the effect of bempedoic acid on CV morbidity and mortality in patients with CVD, or at high risk for CVD who are only able to tolerate less than lowest approved daily dose of a statin (“statin averse”). It is an event-driven, global, randomized, double-blind, placebo-controlled study that completed enrollment in August 2019 of >14,000 patients.