Daiichi Sankyo Europe Enters into European Licensing Agreement with Esperion for Bempedoic Acid and the Bempedoic Acid / Ezetimibe Combination Tablet

Munich (ots/PRNewswire) -

- Daiichi Sankyo Europe will market oral bempedoic acid and bempedoic
acid / ezetimibe combination tablet in the European Economic Area
and Switzerland
- 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[1]
- Bempedoic acid and its fixed dose combination tablet with ezetimibe
will offer additional treatment options for the large number of
patients unable to reach their target LDL-C level
- This agreement expands Daiichi Sankyo Europe's commitment to
cardiovascular care and the development of innovative, convenient
and affordable treatments
- The marketing authorization application (MAA) is expected to be
submitted to the European Medicines Agency (EMA) in the second
quarter of 2019 with an expected approval in 2020

Daiichi Sankyo Europe has entered into an exclusive licensing
agreement with Esperion Therapeutics (NASDAQ: ESPR) for Daiichi
Sankyo Europe to market bempedoic acid and bempedoic acid / ezetimibe
combination tablet in the European Economic Area and Switzerland.
Daiichi Sankyo Europe will be responsible for commercialization in
these territories while Esperion will be responsible for the
development and manufacturing. This agreement will strengthen Daiichi
Sankyo's cardiovascular portfolio in Europe and will exploit
synergies in the commercialization of the once-daily anticoagulant
LIXIANA®? (edoxaban) and the once-daily antiplatelet Efient®?
(prasugrel).

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 percent are at their target LDL-C level.[2] This is
particularly true for patients who are experiencing adverse drug
reactions (ADRs) under statins and are therefore taking statins only
at the maximum tolerated dose or no statin at all.[3] Bempedoic acid
has a liver specific mode of action and therefore has the potential
to avoid the muscle related ADRs associated with statin therapy.[1]
Bempedoic acid can be used in combination with other lipid lowering
drugs and will offer an affordable oral, once-daily option for
patients not at target.[4]

The robust LDL-C development program that established efficacy and
safety of bempedoic acid was completed in October 2018. It included
almost 4,800 patients, and approximately 3,100 patients were treated
with bempedoic acid with an additional LDL-C lowering of up to 30
percent LDL-C and up to 48 percent LDL-C in combination with
ezetimibe. The results demonstrate that bempedoic acid is well
tolerated and confirm efficacy over an extended period of time. Rates
of treatment-emergent adverse events, muscle-related adverse events
and discontinuations were similar in the bempedoic acid and placebo
treatment groups.[5]

"We are very pleased to announce this license agreement for
bempedoic acid which is a first-in-class treatment that will address
a critical unmet need for patients who have limited options and who
are not reaching their target LDL-cholesterol level," said Rodney
Smith, MD, Head of Medical Affairs at Daiichi Sankyo Europe. "The
Esperion team has conducted a robust, 4,000 patient, high-quality
development program to establish bempedoic acid as an efficacious and
well tolerated therapeutic option and this supports our great
confidence in this product that complements and strengthens our
current cardiovascular portfolio, building on the success of
LIXIANA®," adds Benoit Creveau, Head of Marketing Cardiovascular at
Daiichi Sankyo Europe.

Under the terms of the licensing agreement, Daiichi Sankyo Europe
will make an upfront payment of $150 million to Esperion as well as
additional milestone payments including $150 million upon first
commercial sales and sales royalties. The potential total milestone
payment is up to $900 million.

"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.
Daiichi Sankyo Europe's 1,000 person cardiovascular commercial
organization has a strong history of successfully commercializing
drugs, including their oral anticoagulant, LIXIANA®, and there is
significant overlap among physicians targeted for bempedoic acid,"
said Tim Mayleben, president and chief executive officer of Esperion.
"This agreement represents the first step in the evolution of
Esperion from a pioneering development-stage company to a successful
commercial-stage company."

Esperion completed its Phase 3 LDL-C development program of
bempedoic acid and bempedoic acid / ezetimibe combination tablet in
October 2018. The company plans to submit New Drug Applications
(NDAs) to the Food and Drug Administration (FDA) during the first
quarter of 2019 and Marketing Authorization Applications (MAAs) to
the European Medicines Agency (EMA) during the second quarter of
2019. FDA and EMA LDL-C approval decisions 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 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 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.[6]

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.[5] 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.[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, randomized,
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: http://www.daiichisankyo.com.

Product Communications Contact

Lydia Worms

Daiichi Sankyo Europe GmbH

+49(89)7808751

lydia.worms@daiichi-sankyo.eu

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. 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-Breaking-Clinical-Trial-EUROASPIRE-V.htm. Last accessed
December 20, 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. 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-a
12b-bd00ece6698d. Last accessed December 12, 2018.
6. 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/1639de53-9
494-4299-98a5-0b6f1317678a. Last accessed December 12, 2018.
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/NCT029
93406?term=bempedoic+acid&rank=4. Last accessed December 12, 2018.

December 2018, DSC/18/0020

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