Esperion (NASDAQ:ESPR) today announced that the results of a Phase 2 study evaluating the combination of NEXLETOL® (bempedoic acid) 180 mg Tablet, ezetimibe 10 mg and atorvastatin 20 mg in patients with hypercholesterolemia were published in Atherosclerosis, demonstrating reduction in low-density lipoprotein cholesterol (LDL-C) levels by 60.5% vs. placebo.2
The combination of multiple once-daily, orally administered medicines that impact LDL-C levels via different mechanisms has not been previously studied, and 83% of lipid-lowering treatment is statin monotherapy.3 Even at the highest approved dose, only one-third of patients achieve guideline LDL-C levels of <70 mg/dL with atorvastatin alone.4,5 The results of this Phase 2 study suggest oral once-daily combination therapy could play a role in helping more patients achieve guideline-specified LDL-C goals: at week 6, more than 90% of patients in the treatment arm reached LDL-C levels of <70 mg/dL, and 58% of patients reached a target of <55 mg/dL, compared with no patients in the placebo group meeting either treatment goal.2
“Nearly 9 million patients in the U.S. who take statins are not meeting their cholesterol-lowering goals, indicating a need for additional and combination therapy. On behalf of those patients and their physicians, we are encouraged by the results of this study, and recognize more research is needed,” said Ashley Hall, chief development officer of Esperion. “There are millions of patients globally whose needs aren’t being met by currently available LDL-C lowering treatments, and that is why we continue the urgent work to lower bad cholesterol.”
The aim of this Phase 2 study was to evaluate LDL-C lowering when NEXLETOL was initiated together with ezetimibe (10 mg) and atorvastatin (20 mg), as compared with placebo. The primary endpoint was percent change from baseline in LDL-C vs. placebo, with patients randomized 2:1 to triple therapy (n=43) or placebo (n=20) once daily following a washout of lipid-lowering drugs. After six weeks, all patients randomized to triple therapy showed a reduction in LDL-C, with 95% of patients achieving a decrease in LDL-C ≥50% from baseline. The mean age of patients in this randomized, double-blind, placebo-controlled study was 61.2, and mean baseline LDL-C was 154.8 mg/dL. The majority of study participants were female (63%), supporting Esperion’s commitment to diversity in clinical development.2
Most common adverse events (occurring in two or more patients) in either treatment group included headache, diarrhea, fatigue, increase in hepatic enzyme, osteoarthritis, pain in extremity, rash and muscle spasm. Adverse events were predominantly mild or moderate in severity.2
Although the study was adequately powered, the small number of enrolled patients and short study duration limit the ability to draw deﬁnitive conclusions on long-term treatment effect as well as safety and tolerability.
The dosing of NEXLETOL and ezetimibe used in the treatment arm of the study (180 mg and 10 mg, respectively) is the same as the dosing of the fixed combination drug product NEXLIZET® (bempedoic acid and ezetimibe) Tablet.
The 2020 approval of NEXLETOL in the U.S. was supported by a global pivotal Phase 3 LDL-C-lowering program conducted in more than 3,000 patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). In these studies, NEXLETOL provided an average of 18% placebo-corrected LDL-C lowering at week 12 when used with moderate or high-intensity statins. The most common (incidence ≥2% and greater than placebo) adverse reactions were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia and elevated liver enzymes. NEXLETOL is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C. The effect of bempedoic acid on cardiovascular morbidity and mortality has not been determined and is currently being investigated in 14,014 patients across 32 countries as part of the CLEAR Outcomes study.6 Please see important safety information below.