MUNICH, Germany--(BUSINESS WIRE)--Daiichi Sankyo Europe GmbH (hereafter, ‘Daiichi Sankyo’) and Esperion Therapeutics, Inc. jointly announced today, 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 hypercholesterolaemia (high levels of cholesterol) and to reduce the risk of adverse cardiovascular events.1,2 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 [see full details below].1,2
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.3,7 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.3,4,5,6
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.8 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.9
“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.10 The trial randomised 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.10 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 revascularisation (MACE-4).10
- Results of the key secondary endpoints and subgroup analyses have also been published.10
-ENDS-
About bempedoic acid and its fixed-dose combination with ezetimibe
Bempedoic acid is a first-in-class, oral, once-daily treatment to lower cholesterol, and which can be combined with other oral treatments to help lower cholesterol even further.1,3 Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme which is involved in the production of cholesterol in the liver.11
Bempedoic acid acts on the well-known cholesterol synthesis pathway, upstream of the statin target in the liver, which allows additional LDL-C lowering when added to statin or other LDL-C-lowering therapies.12 Bempedoic acid is not activated in skeletal muscle.11
Bempedoic acid is indicated in adults with established or at high risk for atherosclerotic CV disease to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:1
- in patients on a maximum tolerated dose of statin with or without ezetimibe or,1
- alone or in combination with ezetimibe in patients who are statin-intolerant, or for whom a statin in contraindicated.1
The fixed-dose combination NUSTENDI®▼ combines two complementary ways of reducing cholesterol in a once-daily tablet. NUSTENDI®▼ is a fixed-dose combination (FDC) tablet containing bempedoic acid (the active pharmaceutical ingredient in NILEMDO®) and ezetimibe.
Bempedoic acid / ezetimibe FDC is indicated in adults with established or at high risk for atherosclerotic CV disease to reduce CV risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:2
- in patients on a maximum tolerated dose of statin and not adequately controlled with additional ezetimibe treatment or,2
- in patients who are either statin-intolerant, or for whom a statin in contraindicated, and not adequately controlled with additional ezetimibe treatment or,2
- in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets.2
Daiichi Sankyo Europe has licensed exclusive commercialisation rights to bempedoic acid and its FDC with ezetimibe (marketed as NILEMDO® and NUSTENDI®) in the European Economic Area, UK, Turkey and Switzerland from Esperion and is the full Marketing Authorisation Holder in these territories.
About CLEAR Outcomes trial
The CLEAR Outcomes trial was a Phase 3, event-driven, randomised, multicentre, double-blind, placebo-controlled trial.13 It was designed to evaluate whether treatment with bempedoic acid, marketed as NILEMDO®▼ in Europe, reduced the risk of cardiovascular events in a mixed population of patients who had or were at high-risk for CVD, and for whom primary or secondary CVD prevention was clinically indicated but who were unable or unwilling to receive statin treatment.12
The trial, which was fully enrolled in August 2019, randomized 13,970 patients, aged 18–85 years of age with an average age of 65.5 years at 1,250 sites in 32 countries across the world including 485 sites in Europe.10 Patients had a mean LDL-C at baseline of 3.59 mmol/L (139.0 mg per decilitre) and were randomised to either treatment with bempedoic acid 180 mg daily or matching placebo on a background of guideline-directed medical therapy in both the bempedoic acid and placebo groups.12 Patients were followed up for a median duration of 40.6 months.12
The primary endpoint of the CLEAR Outcomes trial was a four-component composite of major adverse CV events (MACE-4) defined as death from CV causes, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation.12 Key secondary endpoints included: MACE-3, a composite of three major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke); fatal and nonfatal myocardial infarction; coronary revascularisation; fatal and non-fatal stroke; cardiovascular death; and all-cause mortality.12
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops, and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular, and other diseases with high unmet medical need.
For more information, please visit www.daiichi-sankyo.eu
▼ This medicinal product is subject to additional monitoring.
References
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1 European Medicines Agency. Nilemdo - opinion on variation to marketing authorisation. Available at: https://www.ema.europa.eu/en/medicines/human/variation/nilemdo. Last accessed May 2024. |
2 European Medicines Agency. Nustendi - opinion on variation to marketing authorisation. Available at: https://www.ema.europa.eu/en/medicines/human/variation/nustendi. Last accessed May 2024. |
3 The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020. 41;(1): 111–188. |
4 Bandyopadhyay D., et al. Safety and efficacy of extremely low LDL-cholesterol levels and its prospects in hyperlipidemia management. Journal of Lipids. 2018. |
5 Fox, K.M., et al. Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins. Clin Res Cardiol. 2018. 107;(5): 380–388. |
6 Kotseva, K., et al. Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardio. 2019. 26;(8): 824–835. |
7 Timmis, A., et al. European Society of Cardiology: Cardiovascular Disease Statistics 2019. European Heart Journal. 2020. 41;(1) 12–85 |
8 Ballantyne, C.M., et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018. 277: 195–203. |
9 Ballantyne, C.M., et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2019. 27;(6): 593–603. |
10 Nissen, S.E., et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023. 13;388;(15): 1353–1364. |
11 European Medicines Agency. Nustendi® Summary of Product Characteristics. May 2024. Available at: https://www.ema.europa.eu/en/documents/product-information/nustendi-epar-product-information_en.pdf. Last accessed May 2024 |
12 Pinkosky, S.L., et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016. 7: 13457. |
13 Nicholls, S.J., et.al. Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Am Heart J. 2021. 235: 104–112. |
HQ/BIL/05/24/0014
May 2024
