Daiichi Sankyo Europe GmbH and Esperion Therapeutics, Inc. jointly announced that the European Commission (EC) has approved the label update of both NILEMDO® (bempedoic acid) and NUSTENDI® (bempedoic acid /ezetimibe fixed-dose combination (FDC)), as treatments for hypercholesterolemia (high levels of cholesterol) and to reduce the risk of adverse cardiovascular events. The EC?s decisions to update the labels of bempedoic acid and bempedoic acid /ezetimibe FDC are based on the positive CLEAR Outcomes trial results and makes them the first and only LDL-C lowering treatments indicated for primary and secondary prevention of cardiovascular events. The EC decisions follow the previous CHMP opinions received in March this year, and approved bempedoic acid and its fixed-dose combination (bempedoic acid /ezetimibe) for use in adults with established or at high risk for atherosclerotic cardiovascular disease to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors.

In Europe, around one in seven people have high LDL-C levels, and cardiovascular disease is the leading cause of death, responsible for more than 10,000 lives lost every day. However, up to 80% of patients do not reach guideline-recommended LDL-C goals despite receiving treatments such as statins and are at increased risk of a heart attack or stroke. Bempedoic acid is a first-in-class oral treatment which lowers cholesterol, and which can be combined with other treatments to help lower cholesterol even further.

Bempedoic acid provided additional cholesterol lowering of up to 28% on top of statin therapy, compared to placebo. Bempedoic acid /ezetimibe FDC combines two complementary ways of reducing cholesterol in a once-daily tablet, reduced LDL-C by 38% compared to placebo in high-risk patients already taking maximum-tolerated statin therapy. EC approval is based on results of the Phase 3 CLEAR (Cholesterol Lowering via Bempedoic Acid, an ATP citrate lyase (ACL)-Inhibiting Regimen) Outcomes trial.

The trial randomized a total of 13,970 patients aged 18?85 years old and was conducted at 1,250 sites in 32 countries, including 485 sites across Europe. Results from the Phase 3 CLEAR Outcomes trial demonstrated: a 13% reduction in the relative risk of major adverse cardiovascular events defined as a four-component composite of death from cardiovascular (CV) causes, non-fatal myocardial infarction, non-fatal stroke or coronary revascularization (MACE-4). Results of the key secondary endpoints and subgroup analyses have also been published.

NEXLIZET and NEXLETOL are indicated: The bempedoic acid component of NEXLIZET and NEXLETOL is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with: established cardiovascular disease (CVD), or at high risk for a CVD event but without established CVD. As an adjunct to diet: NEXLIZET, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH. NEXLETOL, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.

NEXLIZET and NEXLETOL are contraindicated in patients with a prior hypersensitivity to bempedoic acid or ezetimibe or any of the excipients. Serious hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported. Hyperuricemia: Bempedoic acid, a component of NEXLIZET and NEXLETOL, may increase blood uric acid levels, which may lead to gout.

Hyperuricemia may occur early in treatment and persist throughout treatment, returning to baseline following discontinuation of treatment. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.

Tendon Rupture: Bempedoic acid, a component of NEXLIZET and NEXLETOL, is associated with an increased risk of tendon rupture or injury. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders. Discontinue NEXLIZET or NEXLETOL at the first sign of tendon rupture.

Consider alternative therapy in patients who have a history of tendon disorders or tendon rupture. The most common adverse reactions in the primary hyperlipidemia trials of bempedoic acid, a component of NEXLIZET and NEXLETOL, in =2% of patients and greater than placebo were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. Adverse reactions reported in =2% of patients treated with ezetimibe (a component of NEXLIZET) and at an incidence greater than placebo in clinical trials were upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza.

In the primary hyperlipidemia trials of NEXLIZET, the most commonly reported adverse reactions (incidence =3% and greater than placebo) observed with NEXLIZET, but not observed in clinical trials of bempedoic acid or ezetimibe, were urinary tract infection, nasopharyngitis, and constipation. The most common adverse reactions in the cardiovascular outcomes trial for bempedoic acid, a component of NEXLIZET and NEXLETOL, at an incidence of =2% and 0.5% greater than placebo were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis. Discontinue NEXLIZET or NEXLETOL when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Because of the potential for serious adverse reactions in a breast-fed infant, breastfeeding is not recommended during treatment with NEXLIZET or NEXLETOL.