The addition of bempedoic acid to maximally-tolerated statins resulted in a significant lowering of low-density lipoprotein (LDL) cholesterol in patients at high cardiovascular risk, according to findings from the CLEAR Wisdom trial.
The phase 3 study randomized 779 patients diagnosed with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia (LDL-C ≥70mg/dL) to receive either bempedoic acid (n=522), or placebo (n=257) once daily for 52 weeks. The primary end point of the study was the percent change from baseline in LDL-C at Week 12; secondary end points included changes from baseline in non-high density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein.
Results showed that at Week 12, treatment with bempedoic acid was associated with a significant reduction in LDL-C compared with placebo (–15.1% vs 2.4%, respectively; difference: –17.4% [95% CI, –21.0% to –13.9%]; P <.001). Improvements in LDL-C were found to be maintained throughout the 52-week treatment period.
Moreover, study authors reported “significant reductions with bempedoic acid vs placebo were observed at Week 12 for non-high-density lipoprotein cholesterol (–10.8% vs 2.3%; difference: –13.0% [95% CI, –16.3% to –9.8%]; P <.001), total cholesterol (–9.9% vs 1.3%; difference: –11.2% [95% CI, –13.6% to –8.8%]; P <.001), apolipoprotein B (–9.3% vs 3.7%; difference: –13.0% [95% CI, –16.1% to –9.9%]; P <.001), and high-sensitivity C-reactive protein (median: –18.7% vs –9.4%; difference, –8.7% [asymptotic confidence limits, –17.2% to –0.4%]; P =.04).”
With regard to safety, the rate of treatment-emergent adverse events was found to be similar between the bempedoic acid group and placebo group (70% vs 71%; respectively) and most of these adverse events were considered mild to moderate in intensity. Among patients with diabetes, findings from the study showed no worsening of hemoglobin A1c (change from baseline to Week 12: -0.08% in the bempedoic acid group vs +0.13% in the placebo group).
“The CLEAR Wisdom trial demonstrated that bempedoic acid provided additional LDL-C lowering in patients on background maximally-tolerated statin therapy and had an overall adverse event profile that was comparable to placebo,” said Anne C. Goldberg MD, FACP, FAHA, FNLA, Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research at Washington University, St. Louis and lead study author. “These results are consistent with the results reported from the largest long-term phase 3 study of bempedoic acid, Study 1 or CLEAR Harmony. Results across the phase 3 development program show that bempedoic acid has the potential to be a treatment option for high-risk patients who require additional LDL-C lowering.”
Bempedoic acid is a potential first-in-class treatment for hypercholesterolemia. It works by inhibiting adenosine triphosphate citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase, the target of statins. As the drug is not activated in skeletal muscle, it is not expected to induce the myotoxicity commonly associated with statins.
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