Esperion (NASDAQ: ESPR) is pleased to announce that the results
from the 779 patient, 52 week, Phase 3, double-blind, randomized
placebo-controlled study of bempedoic acid (Study 2, also known as
CLEAR Wisdom) were published today in the Journal of the
American Medical Association (JAMA). Bempedoic acid is being
developed as a, convenient, once-daily, oral therapy for the
treatment of patients with elevated low-density lipoprotein
cholesterol (LDL-C) added onto maximally tolerated statin therapy.
Bempedoic acid and the bempedoic acid 180 mg + ezetimibe 10 mg
fixed dose combination (FDC) tablets’ new drug applications (NDAs)
are currently under regulatory review by the U.S. Food and Drug
Administration (FDA), and the marketing authorisation applications
(MAAs) are currently under centralized review by the European
Medicines Agency (EMA).
Study 2 evaluated the long-term safety, tolerability and
efficacy, of bempedoic acid 180 mg versus placebo in 779 patients
with atherosclerotic cardiovascular disease (ASCVD) and/or
heterozygous familial hypercholesterolemia (HeFH) inadequately
controlled with current lipid-modifying therapies, added-on to
maximally tolerated statin therapy, which may mean no statin at
all.
The JAMA publication includes results from the primary efficacy
endpoint of LDL-C lowering at 12-weeks and key secondary endpoints
of safety and tolerability over 52-weeks, including that bempedoic
acid:
- significantly lowered LDL-cholesterol by 17 percent on
background maximally tolerated statin therapy at 12 weeks, and the
effect was durable through 52-weeks;
- significantly lowered high-sensitivity C-reactive protein
(hsCRP), an important marker of the underlying inflammation
associated with cardiovascular disease, by 19 percent, and the
effect was durable through 52-weeks;
- reduced hemoglobin A1c (HbA1c) by 0.21% vs. placebo in patients
with diabetes (n=236) at 12 weeks, favorable glycemic control and
less worsening of diabetes persisted over the 52-week treatment
period;
- showed overall adverse event rates comparable with placebo (BA
70% vs placebo 71%) at 52 weeks, and the proportion of patients
with reported serious adverse events was similar compared with
placebo (BA 20% vs placebo 19%) at 52 weeks; and
- showed adjudicated 3-component major adverse cardiac event
rates of 2.7% with BA and 4.7% with placebo.
“The CLEAR Wisdom trial demonstrated that bempedoic acid
provided additional LDL-cholesterol lowering in patients on
background maximally tolerated statin therapy and had an overall
adverse event profile that was comparable to placebo,” 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 are
consistent with the results reported from the largest long-term
Phase 3 study of bempedoic acid, Study 1 or CLEAR Harmony, which
were published earlier this year in the New England Journal of
Medicine. Results across the Phase 3 development program show that
bempedoic acid has the potential to be a treatment option for
high-risk patients who require additional LDL-C lowering.”
“The results published in JAMA today along with the results from
our three other positive Phase 3 studies show that bempedoic acid
has the potential to be an important new treatment option for
patients with high levels of bad cholesterol despite the use of
maximally tolerated statin therapy”, said Tim M. Mayleben,
president and chief executive officer of Esperion. “While statins
clearly benefit many patients, there is a notable segment of
patients who need additional LDL-C lowering treatment and that
could benefit from a cost-effective and convenient oral, once-daily
therapy that can be added to maximally tolerated statin
therapy.”
Design of Global Pivotal Phase 3 Study 2 (1002-047, also
known as CLEAR Wisdom)
The 52-week, global, pivotal Phase 3 randomized, double-blind,
placebo-controlled, multicenter study evaluated the efficacy and
safety of bempedoic acid 180 mg/day versus placebo. The study was
conducted at 86 sites in North America and Europe. A total of 779
patients were randomized 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 bempedoic
acid’s effects on other markers after 12 weeks of treatment,
including HbA1c and hsCRP, versus placebo.
Bempedoic Acid
Bempedoic acid is our lead, non-statin, oral, once-daily, LDL-C
lowering therapeutic candidate, currently under regulatory review
by the FDA and EMA. With a targeted mechanism of action, bempedoic
acid is a first-in-class, ATP Citrate Lyase (ACL) inhibitor that
lowers LDL-C by reducing cholesterol biosynthesis and up-regulating
the LDL receptor. Bempedoic acid has been observed to reduce hsCRP,
a key marker of inflammation associated with cardiovascular
disease. Completed Phase 3 studies conducted in more than 4,000
patients, with over 2,600 patients treated with bempedoic acid,
demonstrated up to 18 percent placebo corrected LDL-C lowering when
used with moderate- and high-intensity statins and 21 to 28 percent
placebo corrected LDL-C lowering when used with low dose or no
background statin.
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 therapeutic candidate, currently under
review by the FDA and EMA. Inhibition of ATP Citrate Lyase (ACL) by
bempedoic acid lowers LDL-C by reducing cholesterol biosynthesis
and 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. Phase 3 data demonstrated
that this combination resulted in a 29 percent placebo corrected
LDL-C lowering when used with maximally tolerated statins, a 44
percent LDL-C lowering when used with no background statin
(post-hoc analysis), and a 34 percent reduction in high sensitivity
C-reactive protein (hsCRP).
CLEAR Cardiovascular Outcomes
Trial
The effect of bempedoic acid on cardiovascular morbidity and
mortality has not yet been determined. Esperion 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 averse." The CVOT
— known as CLEAR Cardiovascular Outcomes Trial — is an
event-driven, global, randomized, double-blind, placebo-controlled
study that completed enrollment in August 2019 of 14,032 patients
with hypercholesterolemia and high CVD risk at over 1,400 sites in
32 countries.
Esperion Therapeutics’ Commitment to Patients with
Hyperlipidemia
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 averse — leaving them at
high risk for cardiovascular events1. In the United States, 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 threshold2.
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.
Esperion Therapeutics
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. 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 bempedoic acid tablet and the bempedoic acid /
ezetimibe fixed dose combination tablet, the therapeutic potential
of, and the clinical development plan for bempedoic acid tablet and
the bempedoic acid / ezetimibe fixed dose combination tablet,
including Esperion's timing, designs, plans for announcement of
results regarding its CLEAR Outcomes study and other ongoing
clinical studies for bempedoic acid tablet and the bempedoic acid /
ezetimibe combination fixed dose tablet, timing for the review and
approval of the NDAs and the MAAs, and Esperion's expectations for
the market for therapies to lower LDL-C, including the market
adoption of bempedoic acid tablet and the bempedoic acid /
ezetimibe fixed dose combination tablet, 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 notwithstanding the
completion of Esperion’s Phase 3 clinical development program for
LDL-C lowering, the FDA or EMA may require additional development
in connection with seeking regulatory approval, 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.
References1 Esperion market research on file:
research project interviewing 350 physicians. Esperion
Therapeutics, Inc. Sept-Oct 2018.
2 Data on file: analysis of NHANES database. Esperion
Therapeutics, Inc. 2018.
Investor Contact: Alex Schwartz Esperion
734-249-3386 aschwartz@esperion.com
Media Contact: Elliot Fox W2Opure 212-257-6724
efox@purecommunications.com
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