MUNICH, Germany—Results from the Daiichi Sankyo Europe GmbH 12-week Phase 3 bempedoic acid/ezetimibe FDC tablet study, published in the European Journal of Preventative Cardiology, showed that the combination significantly lowered LDL-C cholesterol and C-reactive protein (CRP). The study evaluated the efficacy, safety and tolerability of the tablet combination in patients with hypercholesterolemia and a history of atherosclerotic cardiovascular disease, or who are at high risk for atherosclerotic cardiovascular disease, receiving maximally tolerated statin therapy.
Also known as Study 053, the clinical trial demonstrated that the bempedoic acid/ezetimibe fixed-dose combination (FDC) tablet—an oral, once-daily ATP citrate lyase (ACL) inhibitor—reduces cholesterol synthesis in the liver. The tablet lowered LDL-C by 38 percent (placebo-corrected) and reduced hsCRP by 35 percent (from baseline) in patients receiving maximally tolerated statin therapy. It had a favorable safety profile and was well tolerated, according to the article. Bempedoic acid and the FDC tablet are in the process of regulatory review from the European Medicines Agency (EMA) and by the U.S. Food and Drug Administration (FDA).
With a targeted mechanism of action, bempedoic acid is a first-in-class, complementary, once-daily oral ATP citrate lyase inhibitor that reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor, according to Daiichi Sankyo. The bempedoic acid/ezetimibe fixed-dose combination tablet is a non-statin, orally available therapy characterized by local (hepatocyte) inhibition of cholesterol synthesis (bempedoic acid) and suppression of cholesterol absorption (ezetimibe). Inhibition of ATP citrate lyase by bempedoic acid ultimately lowers circulating LDL-C following the up-regulation of hepatocyte LDL receptors. In addition, suppression of Niemann-Pick C1-Like 1 (NPC1L1) by ezetimibe results in reduced absorption of cholesterol from the gastrointestinal tract, reducing delivery of cholesterol to the liver and upregulating the LDL receptors.
As Dr. Christie M. Ballantyne, professor of medicine at the Baylor College of Medicine and lead study author, explained, “The results of this study show that the bempedoic acid/ezetimibe FDC tablet provided significant additional LDL-C lowering and hsCRP reductions when added to maximally tolerated statin therapy. For patients who are not at their goal levels despite currently accessible therapies, the LDL-C lowering and hsCRP reductions seen with the bempedoic acid / ezetimibe FDC tablet support that this could be a very important treatment option.”
While statins have been used to manage hypercholesterolemia, some patients are at high risk of cardiovascular disease (CVD) and are unable to reach their target LDL-C level because of insufficient statin efficacy at maximally tolerated doses. Only 22 to 32 percent of very high-risk patients are believed to be at their target LDL-C level.
“We are pleased to report the superior LDL-C and hsCRP-lowering benefits vs. placebo that the FDC of bempedoic acid with ezetimibe brings to patients at high risk of CVD who do not reach their target for DL-C despite being on maximally tolerated statin therapy,” commented Dr. Wolfgang Zierhut, head of the antithrombotic and cardiovascular medical affairs department at Daiichi Sankyo Europe. “These results add to the growing body of evidence supporting bempedoic acid and the bempedoic acid/ezetimibe FDC tablet. With its liver-specific mode of action, bempedoic acid avoids the debilitating muscle-related side effects that are often associated with statins and could serve as a valuable complementary treatment option to hypercholesterolemia patients who are not reaching their goals with existing treatment options.”
The Phase 3, double-blind clinical trial randomized 382 adult patients at high CVD risk because of atherosclerotic CVD, heterozygous familial hypercholesterolemia or multiple risk factors. Patients were randomized to treatment with the FDC, bempedoic acid 180 mg, ezetimibe 10 mg or placebo added to stable background statin therapy for 12 weeks. The primary efficacy endpoint was the percent change from baseline to week 12 in LDL-C. Among the 301 patients included in this analysis, FDC lowered LDL-C significantly more than placebo, ezetimibe alone or bempedoic acid alone. The FDC lowered LDL-C levels similarly across subgroups, including patients receiving high-intensity, other-intensity or no statin therapy. There were also improvements in secondary efficacy endpoints, including hsCRP. In this trial, FDC treatment had a generally similar safety profile to bempedoic acid, ezetimibe or placebo.