ANN ARBOR—Esperion Therapeutics Inc. (Nasdaq: ESPR), the Ann Arbor-based developer of cholesterol-lowering drugs, announced that the results of a Phase 2 study evaluating the combination of its Nexletol (bempedoic acid) 180 mg Tablet, in combination with ezetimibe 10 mg and atorvastatin 20 mg, reduced low-density lipoprotein cholesterol, the so-called bad cholesterol, by 60.5 percent in patients vs. those receiving a placebo.
The study was published in the peer-reviewed scientific journal Atherosclerosis.
The combination of multiple once-daily, orally administered medicines that impact LDL-C levels via different mechanisms has not been previously studied, and 83 percent of lipid-lowering treatment uses statin drugs alone. Even with the highest approved dose, only one-third of patients achieve guideline LDL-C levels of less than 70 milligrams per deciliter with atorvastatin alone. 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 90d percen of patients in the treatment arm reached LDL-C levels of less than 70 mg/dL, and 58 percent of patients reached a target of less than 55 mg/dL, compared with no patients in the placebo group meeting either treatment goal.
“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,” said Ashley Hall, chief development officer of Esperion. “On behalf of those patients and their physicians, we are encouraged by the results of this study, and recognize more research is needed. 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.”
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.
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 United States was supported by a 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 percent placebo-corrected LDL-C lowering at week 12 when used with moderate or high-intensity statins. The most common (incidence of greater than or equal to 2 percent, 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.
Nexletol reduces cholesterol by a different means than earlier stain drugs. It’s intended for those who suffer unpleasant side effects from statins, including muscle weakiness. More at www.esperion.com.