MUNICH, Germany--(BUSINESS WIRE)--Daiichi Sankyo Europe GmbH (hereafter, ‘Daiichi Sankyo’) and Esperion Therapeutics, Inc. jointly announced today, that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted positive opinions for the label update of both bempedoic acid (marketed as NILEMDO®▼) and the bempedoic acid / ezetimibe fixed dose combination (FDC) (marketed as NUSTENDI®▼ ), recommending their approval as treatments to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk.2
The existing label of bempedoic acid (NILEMDO®▼) provides authorisation for adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:2
- in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or2
- alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.2
The CHMP recommended adopting an update to this label, with which bempedoic acid is also indicated 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:2
- in patients on a maximum tolerated dose of a statin with or without ezetimibe, or2
- alone or in combination with ezetimibe in patients who are statin-intolerant, or for whom a statin is contraindicated.2
The existing label of bempedoic acid / ezetimibe FDC tablet (NUSTENDI®▼) provides authorisation of its use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:2
- in combination with a statin in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin in addition to ezetimibe2, or
- alone in patients who are either statin-intolerant or for whom a statin is contraindicated, and are unable to reach LDL-C goals with ezetimibe alone2,
- in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin2.
Additionally, the CHMP recommends an update of the bempedoic acid / ezetimibe label to amend its indication 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 factors2:
- in patients on a maximum tolerated dose of a statin and not adequately controlled with additional ezetimibe treatment2 or,
- in patients who are either statin-intolerant, or for whom a statin is contraindicated, and not adequately controlled with ezetimibe treatment2 or,
- in patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets2.
“The positive CHMP opinion is a crucial milestone towards improved treatment outcomes, as we are now able to address even better the unmet needs of cardiovascular care and prevention among patients in Europe. This first-in-class medicine with proven efficacy in reducing hypercholesterolaemia and preventing cardiovascular risks, is a testament to our tireless efforts to help improve the cardiovascular treatment landscape. The opinion further reinforces our confidence towards continued commitment of supporting clinical communities and healthcare ecosystems across Europe,” said Oliver Appelhans, Head of Europe Specialty Division, Daiichi Sankyo Europe GmbH.
“We are thrilled with the positive CHMP opinion, 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 latest regulatory milestone further bolsters our efforts to work towards delivering innovative treatment options to manage cardiovascular risk for patients with elevated LDL-C.”
The CHMP positive opinions are based on analysis from the Phase 3 CLEAR (Cholesterol Lowering via Bempedoic Acid, an ATP citrate lyase (ACL)-Inhibiting Regimen) Outcomes trial1. The study enrolled a total of 13,970 patients aged 18-85 years old, and took place at 1,250 sites in 32 countries, including 485 sites across Europe1. 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)1.
- Results of the key secondary endpoints and subgroup analyses have been published1.
The CHMP is a scientific committee of the EMA that reviews medical product applications on their scientific and clinical merit. The European Commission will review the CHMP opinions and is expected to deliver its final decision in the mid of the year 2024.
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About CLEAR Outcomes trial
The CLEAR Outcomes trial was a Phase 3, event-driven, randomised, multicenter, double-blind, placebo-controlled trial3. It was designed to evaluate whether treatment with bempedoic acid, marketed as NILEMDO®▼ in Europe, reduces 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 treatment3.
The study, 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 Europe3. 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 groups3. Patients were followed up for a median duration of 40.6 months3.
The primary endpoint of the CLEAR Outcomes study 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 revascularisation3. 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 mortality3.
About bempedoic acid
Bempedoic acid (commercialised in the European Economic Area, Turkey and Switzerland as NILEMDO®▼) is a first-in-class, oral treatment to lower cholesterol, and which can be combined with other oral treatments to help lower cholesterol even further4. Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme which is involved in the production of cholesterol in the liver4.
Bempedoic acid has been approved for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet4:
- in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or
- alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
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 lipid-lowering therapies5. Due to its unique mechanism of action, bempedoic acid is not activated in skeletal muscle4.
Daiichi Sankyo Europe has licensed exclusive commercialisation rights to bempedoic acid in the European Economic Area, Turkey and Switzerland from Esperion and is the full Marketing Authorisation Holder in these territories.
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.daiichisankyo.com
▼ This medicinal product is subject to additional monitoring.
References
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1 Nissen SE, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023. 13;388(15):1353-1364. |
2 European Medicines Agency (EMA) March 2024. Available at: Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2024 | European Medicines Agency (europa.eu) |
3 Nicholls SJ, 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. |
4 European Medicines Agency. Nilemdo® Summary of Product Characteristics. March 2024. Available at: Nilemdo | European Medicines Agency (europa.eu) |
5 Pinkosky SL, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016; 7: 13457. |
