MUNICH, January 7, 2019 /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:
- Pinkosky L. et al. Liver-specific ATP-citrate lyase
inhibition by bempedoic acid decreases LDL-C and attenuates
atherosclerosis. Nature. 2016: 10.1038.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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=bempedoic+acid&rank=4.
Last accessed December 12, 2018.
December 2018, DSC/18/0020