CLEAR Wisdom Demonstrated First-in-class, Oral, Once-daily, ACL Inhibitor Bempedoic Acid Significantly Lowered LDL-Cholesterol and Reduced hsCRP

- Late-Breaking Presentation of Final Results of Bempedoic Acid
Pivotal Phase 3 CLEAR Wisdom at the American College of Cardiology
(ACC) 2019 Scientific Sessions

- Over 52-Weeks, Bempedoic Acid was Observed to be Safe,
Well-Tolerated and Adverse Event Profile was Similar to that of
Placebo[1]

- Bempedoic Acid is an Oral, Once-Daily ATP Citrate Lyase (ACL)
Inhibitor that Reduces Cholesterol and Fatty Acid Synthesis in the
Liver

Munich and Ann Arbor, Michigan (ots/PRNewswire) - Daiichi Sankyo
Europe GMbH (hereafter, 'Daiichi Sankyo') and Esperion (NASDAQ: ESPR)
today announced that the Phase 3 results from CLEAR Wisdom of
first-in-class, oral, once-daily ATP citrate lyase (ACL) inhibitor,
bempedoic acid, were presented at the ACC Scientific Sessions & Expo
in New Orleans. Bempedoic acid is being developed as a complementary,
convenient, once-daily, oral therapy for the treatment of patients
with elevated low-density lipoprotein cholesterol (LDL-C). Bempedoic
acid and the bempedoic acid / ezetimibe combination tablet new drug
applications have been submitted to the United States Food and Drug
Administration (FDA), and are under regulatory review for marketing
authorisation by the European Medicines Agency (EMA).

The late-breaking presentation, titled "Efficacy and Safety of
Bempedoic Acid Added to Maximally Tolerated Statins in Patients with
Hypercholesterolemia and High Cardiovascular Risk: The CLEAR Wisdom
Trial", was delivered by Anne C. Goldberg MD, FACP, FAHA, FNLA,
Professor of Medicine, Division of Endocrinology, Metabolism and
Lipid Research at Washington University, St. Louis.

The presentation highlighted results from the primary endpoint of
LDL-C lowering at 12-weeks and key secondary endpoint of safety and
tolerability over 52-weeks, including that bempedoic acid:1

- significantly lowered LDL-C by 17% on background maximally
tolerated statin therapy, and maintained significant reductions in
LDL-C for 52 weeks;
- significantly lowered high sensitivity C-reactive protein (hsCRP),
an important marker of the underlying inflammation associated with
cardiovascular disease, by 19%;
- had an adverse event profile that was similar to that of placebo
(70.1% vs 70.8%) and serious adverse event profile that was
generally similar to that of placebo (20.3% vs 18.7%);
- showed no worsening of glycemic measurements in patients with a
history of diabetes, including a 12-week reduction in haemoglobin
A1c of 0.21%.

There is a significant need for additional treatment options for
the large number of patients in Europe with hypercholesterolemia who
are not at their target LDL-C level. Even in very high-risk patients,
only 32% are at their target LDL-C level.[2] Bempedoic acid has a
liver specific mode of action and therefore has the potential to
avoid the muscle related adverse drug reactions associated with
statin therapy.[3] Bempedoic acid can be used in combination with
other lipid lowering drugs and will offer an oral, once-daily option
for patients not at target.[4]

"In the CLEAR Wisdom Trial, bempedoic acid was shown to be safe
and well-tolerated and also provided significant lowering of LDL-C in
patients on background maximally tolerated statin therapy," said Anne
C. Goldberg MD, FACP, FAHA, FNLA, Professor of Medicine, Division of
Endocrinology, Metabolism and Lipid Research at Washington
University, St. Louis and lead study author. "These results show that
bempedoic acid could be an important new, oral treatment option for
high-risk patients who require additional LDL-C lowering."

"CLEAR Wisdom was the final clinical study in the five Phase 3
study research programme, designed to deliver significant evidence on
the benefits of bempedoic acid in patients in need of additional
LDL-C lowering. We are pleased to reiterate the findings from our
topline results, which showed that bempedoic acid had an adverse
event profile similar to placebo, as well as significantly lowered
LDL-C and hsCRP over the course of the study," said Wolfgang Zierhut,
MD, Head of Antithrombotic and Cardiovascular Medical Affairs
Department at Daiichi Sankyo Europe. "We continue to be encouraged by
these results and believe that bempedoic acid and the bempedoic acid
/ ezetimibe combination tablet will serve an important unmet need for
patients who require additional LDL-C lowering and are not reaching
their goals with existing treatment options."

Design of Global Pivotal Phase 3 CLEAR Wisdom (1002-047, also
known as Study 2)

The 52-week, global pivotal Phase 3 randomised, double-blind,
placebo-controlled, multicenter study evaluated the efficacy and
safety of bempedoic acid 180 mg/day versus placebo. The study was
conducted at 93 sites in North America and Europe. A total of 779
patients were randomised 2:1 to receive bempedoic acid or placebo.
The primary efficacy objective was to assess the 12-week LDL-C
lowering efficacy of bempedoic acid versus placebo. Secondary
objectives included evaluating the safety and tolerability of
bempedoic acid versus placebo, the 24-week and 52-week LDL-C lowering
efficacy of bempedoic acid versus placebo, and its effects on other
risk markers after 12 weeks of treatment, including hsCRP.

Bempedoic Acid / Ezetimibe 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 combination
tablet is our lead, 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 safe and
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
hsCRP. [5]

Bempedoic Acid

With a targeted mechanism of action, bempedoic acid is a
first-in-class, complementary, orally available, once-daily ATP
Citrate Lyase inhibitor that, reduces cholesterol biosynthesis and
lowers LDL-C by up-regulating the LDL receptor. Similar to statins,
bempedoic acid also reduces hsCRP, a key marker of inflammation
associated with cardiovascular disease.[6] Completed Phase 2 and
Phase 3 studies conducted in almost 4,800 patients, and approximately
3,100 patients treated with bempedoic acid, have demonstrated 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.4

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, global,
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.[7]

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.

Esperion's Commitment to Patients with Hypercholesterolemia

High levels of LDL-C can lead to a build-up of fat and cholesterol
in and on artery walls (known as atherosclerosis), potentially
leading to cardiovascular events, including heart attack or stroke.
In the U.S., 96 million people, or more than 37 percent of the adult
population have elevated LDL-C. There are approximately 18 million
people in the U.S. with atherosclerotic cardiovascular disease
(ASCVD) who live with elevated levels of LDL-C despite taking
maximally tolerated lipid-modifying therapy - including individuals
considered statin intolerant - leaving them at high risk for
cardiovascular events. More than 50 percent of ASCVD patients who are
not able to reach their LDL-C goals with statins alone, need less
than a 40 percent reduction to reach their LDL-C threshold.

Esperion's mission as the Lipid Management Company is to deliver
once-daily, oral therapies that complement existing oral drugs to
provide the additional LDL-C lowering that these patients need.

The Lipid Management Company

Esperion is the Lipid Management Company passionately committed to
developing and commercialising complementary, cost-effective,
convenient, 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 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.

Forward-looking statements

This press release contains forward-looking statements and
information about future developments in the sector, and the legal
and business conditions of DAIICHI SANKYO Co., Ltd. Such
forward-looking statements are uncertain and are subject at all times
to the risks of change, particularly to the usual risks faced by a
global pharmaceutical company, including the impact of the prices for
products and raw materials, medication safety, changes in exchange
rates, government regulations, employee relations, taxes, political
instability and terrorism as well as the results of independent
demands and governmental inquiries that affect the affairs of the
company. All forward-looking statements contained in this release
hold true as of the date of publication. They do not represent any
guarantee of future performance. Actual events and developments could
differ materially from the forward-looking statements that are
explicitly expressed or implied in these statements. DAIICHI SANKYO
Co., Ltd. assume no responsibility for the updating of such
forward-looking statements about future developments of the sector,
legal and business conditions and the company.

References

[1] Goldberg AC. et al. Efficacy and Safety of Bempedoic Acid
Added to Maximally Tolerated Statins in Patients with
Hypercholesterolemia and High Cardiovascular Risk: The CLEAR Wisdom
Trial. Presented at ACC 2019.

[2] De Backer G. et al. Lipid Management of Patients with Coronary
Heart Disease in 27 Countries in Europe: Results of EUROASPIRE V
Survey of the European Society of Cardiology. Presented at EAS 2018.
Available at: https://www.eas-society.org/news/399857/EAS2018-Late-Br
eaking-Clinical-Trial-EUROASPIRE-V.htm Last accessed March 2019

[3] Pinkosky L. et al. Liver-specific ATP-citrate lyase inhibition
by bempedoic acid decreases LDL-C and attenuates atherosclerosis.
Nature, 2016; 10:1038.

[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; 10:556-567

[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/163
9de53-9494-4299-98a5-0b6f1317678a. Last accessed March 8, 2019.

[6] 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 March 8, 2019.

[7] 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.

Investor Contact
Alex Schwartz
Esperion
+1-734-249-3386
aschwartz@esperion.com

Media Contact
Elliot Fox
W2O Group
+1-212-257-6724
efox@purecommunications.com

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

March 2019 BEM/19/0003

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

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