First-In-Class Cholesterol-Lowering Treatment & its Combination With Ezetimibe Approved In Europe to Treat Hypercholesterolemia & Significantly Reduce Cardiovascular Risk

Daiichi Sankyo Europe GmbH  and Esperion Therapeutics, Inc. jointly announced 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 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.

“Today’s announcement marks a pivotal moment in our ongoing efforts to reduce cardiovascular risk. With the new indication, which covers both primary and secondary prevention, we can support healthcare professionals to better meet the treatment needs in their daily practice. At the same time, we’re confident it will reassure patients that their medication truly addresses their CV risk. This reaffirms our commitment to be a trusted ally in improving cardiovascular care throughout Europe,” said Oliver Appelhans, Head of Europe Specialty Division, Daiichi Sankyo Europe GmbH.

“We are delighted with the European Commission’s approval, which reflects the significant cardiovascular risk reduction benefit that the bempedoic acid global franchise brings to patients worldwide,” said Sheldon Koenig, President and CEO, Esperion. “This further supports our efforts towards delivering innovative treatment options to manage cardiovascular risk for patients with elevated LDL-C.”

“Today’s positive label update reaffirms the efficacy of both these treatments for reducing LDL-C levels and ultimately reducing patients’ risk of serious cardiovascular events,” said Professor Alberico Catapano, University of Milan, Italy. “The announcement will provide doctors across Europe with further confidence in prescribing bempedoic acid, alone or in combination with ezetimibe, for managing the needs of their patients.”

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.

INDICATION 
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.

At Esperion, we discover, develop, and commercialize innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases. The status quo is not meeting the health needs of millions of people with high cholesterol – that is why our team of passionate industry leaders is breaking through the barriers that prevent patients from reaching their goals. Providers are moving toward reducing LDL-cholesterol levels as low as possible, as soon as possible; we provide the next steps to help get patients there. Because when it comes to high cholesterol, getting to goal is not optional. It is our life’s work. For more information, visit esperion.com.

CLEAR Outcomes is part of the CLEAR clinical research program for NEXLETOL (bempedoic acid) Tablet and NEXLIZET (bempedoic acid and ezetimibe) Tablet. The CLEAR Program seeks to generate important clinical evidence on the safety and efficacy of bempedoic acid, a first in a class ATP citrate lyase inhibitor contained in NEXLETOL and NEXLIZET and its potential role in addressing additional critical unmet medical needs. More than 60,000 people will have participated in the program by the time of its completion. The CLEAR Program includes 5 label-enabling Phase 3 studies as well as other key Phase IV studies with the potential to reach more than 70 million people with or at risk for CVD based on elevated LDL-C.