Esperion (NASDAQ: ESPR) today announced that the results of a Phase
2 study evaluating the combination of NEXLETOL® (bempedoic acid)
180 mg Tablet, ezetimibe 10 mg and atorvastatin 20 mg in patients
with hypercholesterolemia were published in Atherosclerosis,
demonstrating reduction in low-density lipoprotein cholesterol
(LDL-C) levels by 60.5% vs. placebo.2
The combination of multiple once-daily, orally administered
medicines that impact LDL-C levels via different mechanisms has not
been previously studied, and 83% of lipid-lowering treatment is
statin monotherapy.3 Even at the highest approved dose, only
one-third of patients achieve guideline LDL-C levels of <70
mg/dL with atorvastatin alone.4,5 The results of this Phase 2 study
suggest oral once-daily combination therapy could play a role in
helping more patients achieve guideline-specified LDL-C goals: at
week 6, more than 90% of patients in the treatment arm reached
LDL-C levels of <70 mg/dL, and 58% of patients reached a target
of <55 mg/dL, compared with no patients in the placebo group
meeting either treatment goal.2
“Nearly 9 million patients in the U.S. who take statins are not
meeting their cholesterol-lowering goals, indicating a need for
additional and combination therapy. On behalf of those patients and
their physicians, we are encouraged by the results of this study,
and recognize more research is needed,” said Ashley Hall, chief
development officer of Esperion. “There are millions of patients
globally whose needs aren’t being met by currently available LDL-C
lowering treatments, and that is why we continue the urgent work to
lower bad cholesterol.”
The aim of this Phase 2 study was to evaluate LDL-C lowering
when NEXLETOL was initiated together with ezetimibe (10 mg) and
atorvastatin (20 mg), as compared with placebo. The primary
endpoint was percent change from baseline in LDL-C vs. placebo,
with patients randomized 2:1 to triple therapy (n=43) or placebo
(n=20) once daily following a washout of lipid-lowering drugs.
After six weeks, all patients randomized to triple therapy showed a
reduction in LDL-C, with 95% of patients achieving a decrease in
LDL-C ≥50% from baseline. The mean age of patients in this
randomized, double-blind, placebo-controlled study was 61.2, and
mean baseline LDL-C was 154.8 mg/dL. The majority of study
participants were female (63%), supporting Esperion’s commitment to
diversity in clinical development.2
Most common adverse events (occurring in two or more patients)
in either treatment group included headache, diarrhea, fatigue,
increase in hepatic enzyme, osteoarthritis, pain in extremity, rash
and muscle spasm. Adverse events were predominantly mild or
moderate in severity.2
Although the study was adequately powered, the small number of
enrolled patients and short study duration limit the ability to
draw definitive conclusions on long-term treatment effect as well as
safety and tolerability.
The dosing of NEXLETOL and ezetimibe used in the treatment arm
of the study (180 mg and 10 mg, respectively) is the same as the
dosing of the fixed combination drug product NEXLIZET® (bempedoic
acid and ezetimibe) Tablet.
The 2020 approval of NEXLETOL in the U.S. was supported by a
global pivotal Phase 3 LDL-C-lowering program conducted in more
than 3,000 patients with atherosclerotic cardiovascular disease
(ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH).
In these studies, NEXLETOL provided an average of 18%
placebo-corrected LDL-C lowering at week 12 when used with moderate
or high-intensity statins. The most common (incidence ≥2% and
greater than placebo) adverse reactions were upper respiratory
tract infection, muscle spasms, hyperuricemia, back pain, abdominal
pain or discomfort, bronchitis, pain in extremity, anemia and
elevated liver enzymes. NEXLETOL is indicated as an adjunct to diet
and maximally tolerated statin therapy for the treatment of adults
with HeFH or established ASCVD who require additional lowering of
LDL-C. The effect of bempedoic acid on cardiovascular morbidity and
mortality has not been determined and is currently being
investigated in 14,014 patients across 32 countries as part of the
CLEAR Outcomes study.6 Please see important safety information
below.
NEXLETOL® (bempedoic
acid) Tablet and NEXLIZET®
(bempedoic acid and ezetimibe) Tablet
Indication and Limitation of UseNEXLETOL and NEXLIZET are
indicated as adjuncts to diet and maximally tolerated statin
therapy for the treatment of adults with heterozygous familial
hypercholesterolemia or established atherosclerotic cardiovascular
disease who require additional lowering of LDL-C. The effect of
NEXLETOL and NEXLIZET on cardiovascular morbidity and mortality has
not been determined.
Important Safety InformationContraindications: NEXLETOL has no
contraindications. NEXLIZET is contraindicated in patients with a
known hypersensitivity to ezetimibe tablets. Hypersensitivity
reactions including anaphylaxis, angioedema, rash, and urticaria
have been reported with ezetimibe.
Warnings and Precautions:
- Hyperuricemia: Bempedoic acid, a component of NEXLETOL and
NEXLIZET, may increase blood uric acid levels. Hyperuricemia may
occur early in treatment and persist throughout treatment, and may
lead to the development of gout, especially in patients with a
history of gout. Assess uric acid levels periodically as clinically
indicated. Monitor for signs and symptoms of hyperuricemia, and
initiate treatment with urate-lowering drugs as appropriate.
- Tendon Rupture: Bempedoic acid is associated with an increased
risk of tendon rupture or injury. In clinical trials, tendon
rupture occurred in 0.5% of patients treated with bempedoic acid
versus 0% of patients treated with placebo, and involved the
rotator cuff (the shoulder), biceps tendon, or Achilles tendon.
Tendon rupture occurred within weeks to months of starting
bempedoic acid. Tendon rupture may occur more frequently in
patients over 60 years of age, patients taking corticosteroid or
fluoroquinolone drugs, patients with renal failure, and patients
with previous tendon disorders. Discontinue NEXLETOL or NEXLIZET at
the first sign of tendon rupture. Avoid NEXLETOL and NEXLIZET in
patients who have a history of tendon disorders or tendon
rupture.
Adverse Reactions:
- In NEXLETOL clinical trials, the most commonly reported adverse
reactions were upper respiratory tract infection, muscle spasms,
hyperuricemia, back pain, abdominal pain or discomfort, bronchitis,
pain in extremity, anemia, and elevated liver enzymes. Reactions
reported less frequently, but still more often than with placebo,
included benign prostatic hyperplasia and atrial fibrillation.
- In the NEXLIZET clinical trial, the most commonly reported
adverse reactions observed with NEXLIZET, but not observed in
clinical trials of bempedoic acid or ezetimibe, a component of
NEXLIZET, and occurring more frequently than with placebo, were
urinary tract infection, nasopharyngitis, and constipation.
- Adverse reactions reported in clinical trials of ezetimibe, and
occurring at an incidence greater than with placebo, included upper
respiratory tract infection, diarrhea, arthralgia, sinusitis, pain
in extremity, fatigue, and influenza. Other adverse reactions
reported in postmarketing use of ezetimibe included
hypersensitivity reactions, including anaphylaxis, angioedema,
rash, and urticaria; erythema multiforme; myalgia; elevated
creatine phosphokinase; myopathy/rhabdomyolysis; elevations in
liver transaminases; hepatitis; abdominal pain; thrombocytopenia;
pancreatitis; nausea; dizziness; paresthesia; depression; headache;
cholelithiasis; cholecystitis.
Drug Interactions:
- Simvastatin and Pravastatin: Concomitant use with bempedoic
acid results in increased concentrations and increased risk of
simvastatin or pravastatin-related myopathy. Use of either NEXLETOL
or NEXLIZET with greater than 20 mg of simvastatin or 40 mg of
pravastatin should be avoided.
- Cyclosporine: Caution should be exercised when using NEXLIZET
and cyclosporine concomitantly due to increased exposure to both
ezetimibe and cyclosporine. Monitor cyclosporine concentrations in
patients receiving NEXLIZET and cyclosporine. In patients treated
with cyclosporine, the potential effects of the increased exposure
to ezetimibe from concomitant use should be carefully weighed
against the benefits of alterations in lipid levels provided by
NEXLIZET.
- Fibrates: Coadministration of NEXLIZET with fibrates other than
fenofibrate is not recommended. Fenofibrate and ezetimibe may
increase cholesterol excretion into the bile, leading to
cholelithiasis. If cholelithiasis is suspected in a patient
receiving NEXLIZET and fenofibrate, gallbladder studies are
indicated and alternative lipid-lowering therapy should be
considered.
- Cholestyramine: Concomitant use of NEXLIZET and cholestyramine
decreases ezetimibe concentration. This may result in a reduction
of efficacy. Administer NEXLIZET either at least 2 hours before, or
at least 4 hours after, bile acid sequestrants.
Lactation and Pregnancy: It is not recommended that NEXLETOL or
NEXLIZET be taken during breastfeeding. Discontinue NEXLETOL or
NEXLIZET when pregnancy is recognized, unless the benefits of
therapy outweigh the potential risks to the fetus. Based on the
mechanism of action of bempedoic acid, NEXLETOL and NEXLIZET may
cause fetal harm.
You are encouraged to report negative side effects of
prescription drugs to the
FDA. Visit www.fda.gov/medwatch or
call 1-800-FDA-1088 or report side effects to Esperion at
833-377-7633 (833 ESPRMED).
Please see the full Prescribing Information for
NEXLETOL.Please see the full Prescribing
Information for NEXLIZET.
Esperion Therapeutics
ESPERION is The Lipid Management Company. Our goal is lipid
management for everybody, that’s why we work hard to make our
medicines easy to get, easy to take and easy to have. We discover,
develop and commercialize innovative medicines and combinations to
lower cholesterol, especially for patients whose needs aren’t being
met by the status quo. Our entrepreneurial team of industry leaders
is inclusive, passionate and resourceful. We are singularly focused
on managing cholesterol so you can improve your health easily. For
more information, please visit www.esperion.com and follow us on
Twitter at www.twitter.com/EsperionInc.
Forward-Looking StatementsThis press release
contains forward-looking statements that are made pursuant to the
safe harbor provisions of the federal securities laws, including
statements regarding commercialization plans for bempedoic acid
tablet. 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 clinical development
and commercialization plans, or approval of expanded indications,
that existing cash resources may be used more quickly than
anticipated, the impact of COVID-19 on our business, clinical
activities and commercial development plans, and the risks detailed
in Esperion's filings with the Securities and Exchange Commission.
Any forward-looking statements contained in this press release
speak only as of the date hereof, and 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 M. Banach, P.E. Penson,
Lipid-lowering therapies: Better together, Atherosclerosis. 320
(2021) 86–88.
2 J. Rubino, D.E. MacDougall, L.R. Sterling, et al., Combination
of bempedoic acid, ezetimibe, and atorvastatin in patients with
hypercholesterolemia: A randomized clinical trial, Atherosclerosis.
320 (2021) 122–128.
3 K.K. Ray, B. Molemans, W.M. Schoonen, et al., EU-wide
cross-sectional observational study of lipid-modifying therapy use
in secondary and primary care: the DA VINCI study, Eur J Prev
Cardiol (2020), https://doi.org/10.1093/eurjpc/zwaa047.
4 S.M. Grundy, N.J. Stone, A.L. Bailey, et al.,
AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA guideline
on the management of blood cholesterol: a report of the American
college of cardiology/American heart association task force on
clinical practice guidelines, J. Am. Coll. Cardiol. 73 (2018)
e285–e350, 2019.
5 E. Marrett, C. Zhao, N.J. Zhang, et al., Limitations of
real-world treatment with atorvastatin monotherapy for lowering
LDL-C in high-risk cardiovascular patients in the US, Vasc. Health
Risk Manag. 10 (2014) 237–246.
6 S.J. Nicholls et al., Rationale and design of the
CLEAR-outcomes trial: Evaluating the effect of Bempedoic acid on
cardiovascular events in patients with statin intolerance, American
Heart Journal (2020),
https://doi.org/10.1016/j.ahj.2020.10.060.
Contact:Kaitlyn Brosco Esperioncorporateteam@esperion.com
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