Daiichi Sankyo Europe and Esperion Announce Validation of the Marketing Authorisation Application (MAA) for Bempedoic Acid and the Bempedoic Acid / Ezetimibe Fixed Dose Combination Tablet

Munich and Ann Arbor, Michigan (ots/PRNewswire) -

- Application is based on results of a robust development programme,
which demonstrated that bempedoic acid was well tolerated and
efficacious for chronic use
- Bempedoic acid is a first-in-class, oral, once-daily ATP Citrate
Lyase (ACL) inhibitor that reduces cholesterol and fatty acid
synthesis in the liver
- Bempedoic acid expands Daiichi Sankyo Europe's commitment to
cardiovascular care and the development of innovative, convenient
and affordable treatments

Daiichi Sankyo Europe (hereafter, Daiichi Sankyo) and Esperion
Therapeutics Inc. (hereafter, Esperion) announced today the
validation of the Marketing Authorisation Application (MAA) for
bempedoic acid and the bempedoic acid / ezetimibe fixed dose
combination tablet by the European Medicines Agency (EMA). Validation
confirms that the application is complete and commences the
scientific review process by the EMA's Committee for Medicinal
Products for Human Use (CHMP).

Bempedoic acid is an oral, once-daily ATP Citrate Lyase (ACL)
inhibitor that reduces cholesterol and fatty acid synthesis in the
liver.1 Bempedoic acid and the bempedoic acid / ezetimibe fixed dose
combination tablet could become an important treatment option for
patients with hypercholesterolemia who are not yet at their target
LDL-C goals with existing therapies or who have statin intolerance.

This MAA validation for the LDL-C lowering indication is based on
the successful completion of the global pivotal Phase 3 programme,
which demonstrated bempedoic acid was well tolerated and efficacious
for chronic use in almost 4,800 patients. Patients treated with
bempedoic acid produced an additional 20 percent LDL-C lowering when
used with maximally tolerated statins, up to 30 percent LDL-C
lowering as monotherapy, 35 percent LDL-C lowering in combination
with ezetimibe when used with maximally tolerated statins and up to
48 percent LDL-C lowering in combination with ezetimibe as
monotherapy. In the Phase 3 trials, rates of treatment-emergent
adverse events, muscle-related adverse events and discontinuations
were similar in the bempedoic acid and placebo treatment group.2

There is a significant unmet need for patients with elevated LDL-C
who are not reaching their treatment goals with existing therapies.
This is particularly true for patients taking statins only at the
maximum tolerated dose or are statin intolerant and need additional
LDL-C lowering.3 Bempedoic acid has a liver specific mode of action
and therefore has the potential to avoid the muscle related adverse
drug reactions (ADRs) associated with statin therapy. Bempedoic acid
can be used in combination with other lipid lowering drugs and will
offer a once-daily, convienent, oral option for patients not at
target goals.4

Bempedoic acid expands Daiichi Sankyo Europe's commitment to
cardiovascular care and the development of innovative and convenient
treatments.

"Unlike some of the historical cardiovascular players who have
decided to focus their effort on other therapeutic areas, we remain
committed to the cardiovascular field. With bempedoic acid, our
first-in-class treatment, we build on our dedication to address
critical unmet needs for patients in Europe who have limited options
and who are not reaching their target LDL-C level," said Benoit
Creveau, Head of Marketing Cardiovascular at Daiichi Sankyo Europe.

"We are very pleased to partner with Daiichi Sankyo Europe to
establish bempedoic acid as the most preferred LDL-C lowering
treatment option after statins for patients and physicians in Europe.
We expect Daiichi Sankyo Europe's significant cardiovascular reach
and expertise will help establish bempedoic acid and the bempedoic
acid / ezetimibe fixed dose combination tablet as important tools in
physicians' and patients' fight against elevated LDL-C levels," said
Tim Mayleben, President and Chief Executive Officer of Esperion.

"The results from the pivotal Phase 3 LDL-C development programme
of bempedoic acid and bempedoic acid / ezetimibe fixed dose
combination tablet provide compelling evidence that bempedoic acid is
an efficacious and well tolerated therapeutic option and we hope to
make it available as soon as possible to European patients," adds
Rodney Smith, MD, Head of Medical Affairs at Daiichi Sankyo Europe.

Esperion completed its Phase 3 LDL-C development programme of
bempedoic acid and the bempedoic acid / ezetimibe fixed dose
combination tablet in October 2018. This robust development programme
forms the bases for FDA and EMA approval decisions that are expected
during the first half of 2020. The global cardiovascular outcomes
trial of bempedoic acid, CLEAR Outcomes, is ongoing, and
cardiovascular risk reduction data are expected during 2022.

Bempedoic Acid / Ezetimibe Fixed Dose Combination Tablet

Through the complementary mechanisms of action of inhibition of
cholesterol synthesis (bempedoic acid) and inhibition of cholesterol
absorption (ezetimibe), the bempedoic acid / ezetimibe fixed dose
combination tablet is a non-statin, orally available, once-daily,
LDL-C lowering therapy. Inhibition of ATP Citrate Lyase (ACL) by
bempedoic acid reduces cholesterol biosynthesis and lowers LDL-C by
up-regulating the LDL receptor. Inhibition of Niemann-Pick C1-Like 1
(NPC1L1) by ezetimibe results in reduced absorption of cholesterol
from the gastrointestinal tract, thereby reducing delivery of
cholesterol to the liver, which in turn upregulates the LDL
receptors. Phase 3 data demonstrated that this well tolerated
combination results in a 35 percent lowering of LDL-C when used with
maximally tolerated statins, a 43 percent lowering of LDL-C when used
as a monotherapy, and a 34 percent reduction in high sensitivity
C-reactive protein (hsCRP). Rates of treatment-emergent adverse
events, muscle-related adverse events and discontinuations were
similar in the bempedoic acid and placebo treatment groups.5

Bempedoic Acid

With a targeted mechanism of action, bempedoic acid is a
first-in-class, complementary, oral, once-daily ATP Citrate Lyase
(ACL) inhibitor that reduces cholesterol and fatty acid biosynthesis
and lowers LDL-C by up-regulating the LDL receptor. Similar to
statins, bempedoic acid also reduces high sensitivity C-reactive
protein (hs-CRP), a key marker of inflammation associated with
cardiovascular disease.2 Bempedoic acid is a prodrug that requires
activation by the very long-chain acyl-CoA synthetase-1 (ACSVL1).
Furthermore, it was demonstrated that the absence of ACSVL1 in
skeletal muscle provides a mechanistic basis for bempedoic acid to
potentially avoid the myotoxicity associated with statin therapy.1
Completed Phase 2 and Phase 3 studies conducted in almost 4,800
patients, and approximately 3,100 patients treated with bempedoic
acid, have produced an additional 20 percent LDL-C lowering when used
with maximally tolerated statins, up to 30 percent LDL-C lowering as
monotherapy, 35 percent LDL-C lowering in combination with ezetimibe
when used with maximally tolerated statins and up to 48 percent LDL-C
lowering in combination with ezetimibe as monotherapy.2 Rates of
treatment-emergent adverse events, muscle-related adverse events and
discontinuations were similar in the bempedoic acid and placebo
treatment groups.5

The effect of bempedoic acid on cardiovascular morbidity and
mortality has not yet been determined. The company initiated a global
cardiovascular outcomes trial (CVOT) to assess the effects of
bempedoic acid on the occurrence of major cardiovascular events in
patients with, or at high risk for, cardiovascular disease (CVD) who
are only able to tolerate less than the lowest approved daily
starting dose of a statin and considered "statin intolerant." The
CVOT - known as CLEAR Outcomes - is an event-driven, randomised,
double-blind, placebo-controlled study expected to enroll
approximately 12,600 patients with hypercholesterolemia and high CVD
risk at over 1,000 sites in approximately 30 countries.6

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address diversified, unmet
medical needs of patients in both mature and emerging markets. With
over 100 years of scientific expertise and a presence in more than 20
countries, Daiichi Sankyo and its 15,000 employees around the world
draw upon a rich legacy of innovation and a robust pipeline of
promising new medicines to help people. In addition to a strong
portfolio of medicines for hypertension and thrombotic disorders,
under the Group's 2025 Vision to become a "Global Pharma Innovator
with Competitive Advantage in Oncology", Daiichi Sankyo research and
development is primarily focused on bringing forth novel therapies in
oncology, including immuno-oncology, with additional focus on new
horizon areas, such as pain management, neurodegenerative diseases,
heart and kidney diseases, and other rare diseases. For more
information, please visit: www.daiichisankyo.com.

About Esperion

Esperion is the Lipid Management Company passionately committed to
developing and commercialising convenient, complementary,
cost-effective, once-daily, oral therapies for the treatment of
patients with elevated LDL-C. Through scientific and clinical
excellence, and a deep understanding of cholesterol biology, the
experienced Lipid Management Team at Esperion is committed to
developing new LDL-C lowering therapies that will make a substantial
impact on reducing global cardiovascular disease; the leading cause
of death around the world. Bempedoic acid and the company's lead
product candidate, the bempedoic acid / ezetimibe fixed dose
combination tablet, are targeted therapies that have been shown to
significantly lower elevated LDL-C levels in patients with
hypercholesterolemia, including patients inadequately treated with
current lipid-modifying therapies. For more information, please visit
www.esperion.com and follow us on Twitter at
https://twitter.com/EsperionInc.

Product Communications Contact:

Lydia Worms
Daiichi Sankyo Europe GmbH
+49(89)7808751
lydia.worms@daiichi-sankyo.eu

Investor Contact:
Alex Schwartz
Esperion
+1-734-249-3386
aschwartz@esperion.com (https://www.globenewswire.com/Tracker?data=i9jpTWYd5kClfc9KaJOf5oRMO4uKlHTJLHimdCeCC7hOVLOy0aR86YTxJaT9350QMhOfY6f52ErcgTDJbZY8fRSwOcuBQnnwAnq6R-tV2foCPHI_MvS5H1yGYszzvgwWUFH4njSCkkCbgfSmu-Uhz8zf-M2hmLjqtDqZlMZtM_MRdWWQ-yChN-_05Esx0mOSBAbPf3WHQTgL2URM8mtMnElQw9eUKsldF8QhPsddaYRMowYpF6BGCoZx88jYX-TKBPTzuEA4AvkX8x-wLkirSA==)

References:

1 Pinkosky L. et al. Liver-specific ATP-citrate lyase inhibition
by bempedoic acid decreases LDL-C and attenuates atherosclerosis.
Nature. 2016: 10.1038.

2 Phase 3 Top-Line Results from Study 2 & Cumulative Phase 3
Program Results. Esperion Investor Presentation. Oct 29, 2018.
Available at https://investor.esperion.com/static-files/32936da0-96f9
-40e5-a12b-bd00ece6698d. Last accessed December 12, 2018.

3 Rosei EA et al. Management of Hypercholesterolemia,
Appropriateness of Therapeutic Approaches and New Drugs in Patients
with High Cardiovascular Risk. High Blood Press Cardiovasc Prev.
2016; 23(3): 217-230.

4 Thompson PD et al. Treatment with ETC-1002 alone and in
combination with ezetimibe lowers LDL cholesterol in
hypercholesterolemic patients with or without statin intolerance.
Journal of Clinical Lipidology. 2016; 10:5560567.

5 Top-Line Results from the Bempedoic Acid / Ezetimibe Combination
Pill Phase 3 Study. Esperion Investor Presentation. Aug 27, 2018.
Available at https://investor.esperion.com/static-files/1639de53-9494
-4299-98a5-0b6f1317678a. Last accessed December 12, 2018.

6 Evaluation of Major Cardiovascular Events in Patients With, or
at High Risk for, Cardiovascular Disease Who Are Statin Intolerant
Treated with Bempedoic Acid (ETC-1002) or Placebo (CLEAR Outcomes).
Available at https://clinicaltrials.gov/ct2/show/NCT02993406?term=bem
pedoic+acid&rank=4. Last accessed December 12, 2018.

February 2019, BEM/19/0001

ots Originaltext: Daiichi Sankyo Europe GmbH
Im Internet recherchierbar: http://www.presseportal.de

Original-Content von: Daiichi Sankyo Europe GmbH, übermittelt durch news aktuell