— Bempedoic Acid / Ezetimibe Combo Pill
Achieved an Additional 35% LDL-C Lowering in Patients on Maximally
Tolerated Statins —
Esperion (NASDAQ: ESPR) today announced positive top-line results
from the pivotal Phase 3 bempedoic acid / ezetimibe combination
pill study (1002-053). This trial was a randomized, double-blind,
parallel group study conducted to evaluate the efficacy and safety
of the bempedoic acid 180 mg / ezetimibe 10 mg combination pill
compared to bempedoic acid, ezetimibe or placebo in patients
treated with maximally tolerated statins.
This pivotal Phase 3, four-arm study design including a primary
endpoint of LDL-C lowering, study statistics and an abbreviated
505(b)(2) regulatory pathway were discussed and agreed to with the
U.S. Food and Drug Administration (FDA) in 2017.
The study included 382 high-risk patients taking maximally
tolerated statins who required additional LDL-C lowering and met
its key efficacy endpoints, including:
- On-treatment analysis LDL-C lowering of 35 percent for the
combination pill at 12 weeks (p<0.001) compared to 3 percent for
placebo, 24 percent for ezetimibe 10 mg (EZE) and 20 percent for
bempedoic acid 180 mg (BA);
- In the intent to treat analysis, LDL-C lowering was 32 percent
for the combination pill compared to 3 percent for placebo
(p<0.001), 21 percent for EZE (p<0.001) and 18 percent for BA
(p<0.001);
- Reduction of 34 percent for the FDC in high-sensitivity
C-reactive protein (hsCRP), an important marker of the underlying
inflammation associated with cardiovascular disease, compared with
an increase in placebo of 4 percent and reductions of 20 percent
for BA and 9 percent for EZE.
- In a post-hoc analysis of patients considered statin
intolerant, the combination pill LDL-C lowering was 43 percent in
the on-treatment analysis compared to a one percent increase for
placebo;
“I’m pleased to see the positive safety and tolerability profile
of the bempedoic acid / ezetimibe fixed-dose combination pill which
was similar to that of ezetimibe alone,” said Christie M.
Ballantyne, M.D., chairman of Esperion’s Phase 3 Executive
Committee and Professor and Chief of Cardiology at Baylor
College of Medicine in Houston. “The LDL-C lowering and hsCRP
reductions seen with the combination are very important
to physicians like me who see these challenging patients every
day, and we need more options for them.”
Safety and Tolerability of Combination Pill Over 12
Weeks
In this 12-week study, the bempedoic acid / ezetimibe combo pill
was observed to be safe and well-tolerated. The results showed no
clinical differences between the FDC, BA, EZE and placebo patient
groups in the occurrence of:
- Serious adverse events (SAEs) with 8 percent, 6 percent, 9
percent and 2 percent, respectively. No SAEs were considered to be
related to study medication;
- Discontinuations due to AEs with 7 percent, 8 percent, 9
percent, and 4 percent, respectively;
- No elevations in liver function tests (ALT/AST) of greater than
three times the upper limit of normal, repeated and confirmed were
observed.
“These pivotal study results of the bempedoic acid / ezetimibe
combination pill are highly compelling. As Lipid Management
experts, we know that 35 percent LDL-C lowering could help more
than six million ASCVD and/or HeFH patients on maximally tolerated
statins achieve LDL-C levels of 70mg/dL or less, an elusive LDL-C
target for most patients today. With a reduction in hsCRP as
a key marker for CV risk reduction based on CANTOS, our 34 percent
hsCRP reduction is truly exceptional,” said Tim M. Mayleben,
president and chief executive officer of Esperion. “With the combo
pill we are confident physicians will have the treatment option
they need to help the more than 12 million Americans with high
LDL-C already taking maximally tolerated statin therapy,
conveniently and cost-effectively achieve lower LDL-C levels.”
Guidance Updates
Topline data from Study 2 (1002-047) are now expected in October
2018 (prior guidance end-of-September 2018). NDAs will be
submitted during the first quarter of 2019.
Design of Pivotal Phase 3 Study 3
(1002-053)
The 12-week, pivotal Phase 3 randomized, double-blind, parallel
group, multicenter study to evaluate the efficacy and safety of
bempedoic acid 180 mg / ezetimibe 10 mg combination pill compared
to bempedoic acid, ezetimibe or placebo in high-risk patients with
ASCVD and/or heterozygous familial hypercholesterolemia or with
multiple risk factors for ASCVD being treated with maximally
tolerated statins. The study was conducted at 78 sites in North
America. A total of 382 patients were randomized 2:2:2:1 to
receive bempedoic acid 180 mg / ezetimibe 10 mg combination pill,
bempedoic acid 180 mg, ezetimibe 10 mg or placebo. The secondary
objectives included assessments of high-sensitivity C-reactive
protein (hsCRP), non-HDL-C, total cholesterol (TC), and
apolipoprotein B (apoB) after 12 weeks of treatment as well as
characterizing the safety and tolerability of the combination pill
versus placebo alone, BA alone, and EZE alone.
Conference Call and Webcast Information
Esperion's Lipid Management Team will host a conference call and
webcast today, Monday, August 27, 2018, at 8:00 a.m. Eastern Time
to discuss these Phase 3 study results. The call can be accessed by
dialing (877) 312-7508 (domestic) or (253) 237-1184 (international)
five minutes prior to the start of the call and providing access
code 3893846. A live audio webcast can be accessed on the investors
and media section of the Esperion website at investor.esperion.com.
Access to the webcast replay will be available approximately two
hours after completion of the call and will be archived on the
Company's website for approximately 90 days.
About Esperion's Global Pivotal Phase 3 LDL-C Lowering
Program
Esperion initiated its global, pivotal, Phase 3 clinical
development program in January 2016 to evaluate the safety,
tolerability and consistent, complementary LDL-C-lowering efficacy
of bempedoic acid and the bempedoic acid / ezetimibe combination
pill in patients with atherosclerotic cardiovascular disease
(ASCVD), or who are at a high risk for ASCVD, with
hypercholesterolemia who continue to have elevated levels of LDL-C
despite the use of maximally-tolerated statins and ezetimibe,
leaving them at high risk for cardiovascular events. The program
includes five studies in approximately 4,000 patients, four for
bempedoic acid and one for the bempedoic acid / ezetimibe
combination pill.
- Two pivotal studies evaluating bempedoic acid (Studies 1 &
2) in 3,009 patients with ASCVD on maximally-tolerated statins,
with top-line results reported in May 2018, and expected in October
2018, respectively;
- Two pivotal studies evaluating bempedoic acid (Studies 3 &
4) in 614 patients with ASCVD, or at a high risk for ASCVD,
considered statin intolerant, with top-line results reported in May
and March 2018, respectively;
- One pivotal study evaluating the bempedoic acid / ezetimibe
combination pill (053 Study) in 382 patients with ASCVD, or at high
risk for ASCVD, on maximally tolerated statins, with top-line
results reported in this press release.
Esperion plans to submit New Drug Applications (NDAs) to the
U.S. Food and Drug Administration (FDA) for bempedoic acid and the
bempedoic acid / ezetimibe combination pill for LDL-C-lowering
indications during the first quarter of 2019. Additionally,
Esperion plans to submit Marketing Authorization Applications
(MAAs) to the European Medicines Agency (EMA) during the second
quarter of 2019.
Bempedoic Acid / Ezetimibe Combination Pill
Through the complementary mechanisms of action of inhibition of
cholesterol synthesis (bempedoic acid) and inhibition of
cholesterol absorption (ezetimibe), the bempedoic acid / ezetimibe
combination pill 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, and a 34 percent reduction in high sensitivity C-reactive
protein (hsCRP).
Bempedoic Acid
With a targeted mechanism of action, bempedoic acid is a
first-in-class, complementary, orally available, once-daily ATP
Citrate Lyase (ACL) 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. Completed
Phase 2 and Phase 3 studies conducted in almost 4,800 patients, and
approximately 2,900 patients treated with bempedoic acid, have
produced LDL-C lowering results of up to 30 percent as monotherapy,
35 percent in combination with ezetimibe on maximally tolerated
statins, 48 percent in combination with ezetimibe as monotherapy,
and an additional 20 percent on maximally tolerated statins.
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 Cholesterol Lowering via Bempedoic Acid,
an ACL-inhibiting Regimen (CLEAR) Outcomes — is an
event-driven, global, randomized, double-blind, placebo-controlled
study expected to enroll approximately 12,600 patients with
hypercholesterolemia and high CVD risk at up to 1,000 sites in
approximately 30 countries.
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., 78 million people, or more than 20
percent of the population, have elevated LDL-C; an additional 73
million people in Europe and 30 million people in Japan also live
with elevated LDL-C. There are approximately 13 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 6 million patients with ASCVD
and/or HeFH on maximally tolerated statins require less than 30
percent additional LDL-C lowering to achieve treatment goals.
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 commercializing 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
combination pill, 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.
Forward-Looking Statements
This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the federal
securities laws, including statements regarding the regulatory
approval pathway for the bempedoic acid / ezetimibe combination
pill and bempedoic acid and the therapeutic potential of, clinical
development plan for, the bempedoic acid / ezetimibe combination
pill and bempedoic acid, including Esperion's timing, designs,
plans and announcement of results regarding its global pivotal
Phase 3 clinical development program for bempedoic acid and the
bempedoic acid / ezetimibe combination pill, Esperion's timing and
plans for submission of NDAs to the FDA and MAAs to the EMA and
Esperion's expectations for the market for therapies to lower
LDL-C, including the market adoption of bempedoic acid and the
bempedoic acid / ezetimibe combination pill, if approved. Any
express or implied statements contained in this press release that
are not statements of historical fact may be deemed to be
forward-looking statements. Forward-looking statements involve
risks and uncertainties that could cause Esperion's actual results
to differ significantly from those projected, including, without
limitation, delays or failures in Esperion’s studies, that positive
results from a clinical study of bempedoic acid may not be
sufficient for FDA or EMA approval or necessarily be predictive of
the results of future or ongoing clinical studies, that existing
cash resources may be used more quickly than anticipated, and the
risks detailed in Esperion's filings with the Securities and
Exchange Commission. Esperion disclaims any obligation or
undertaking to update or revise any forward-looking statements
contained in this press release, other than to the extent required
by law.
Investor Contact: Alex Schwartz Esperion 734-249-3386
aschwartz@esperion.com
Media Contact: Elliot Fox W2O Group 212-257-6724
efox@w2ogroup.com
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