- NILEMDO®▼ (bempedoic acid), a first-in-class, oral treatment
and NUSTENDI®▼ (bempedoic acid / ezetimibe fixed-dose combination)
receive label update approval from the European Commission as
treatments to reduce cardiovascular risk by lowering low-density
lipoprotein cholesterol (LDL-C) levels1,2
- This makes bempedoic acid the first and only LDL-C-lowering
treatment indicated for primary and secondary prevention of
cardiovascular events
- Up to 80% of patients do not reach guideline-recommended LDL-C
goals despite receiving treatments such as statins and remain at an
increased risk of a heart attack or stroke and in need of
additional treatment3,4,5,6
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
_______________________________
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
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240514593487/en/
Media Contact Gillian D’Souza Daiichi Sankyo Europe GmbH
Senior Manager, Public Relations, Specialty Medicines +49 1515
5195599