Bempedoic 

Acid for Treating

Hypercholesterolemia

Presented By:

Samar Al-Omair, B.Sc.

 Contents

• Hypercholesterolemia • Adverse effects

• Bempedoic acid • Advantage over statin
• Approval status • Clinical trials on Bempedoic acid
• Availability • Conclusion
• Mechanism of action • References

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 Hypercholesterolemia

• Hypercholesterlomia is a form of hyperlipidemia,

and hyperlipoproteinemia 

• Cholesterol is transported in the blood plasma

within protein particles (lipoproteins)

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 Hypercholesterolemia (Cont.)

• Cholesterol is required for various body functions including

the synthesis of cell membranes

• Too high level of cholesterol increase the risk of coronary

heart disease.

• High cholesterol is defined as a LDL-cholesterol greater than

190 mg/dl, greater than 160 mg/dl with one major risk factor,
or greater than 130 mg/dl with two cardiovascular risk 4
factors.
 Cholesterol-lowering drugs

Statins Ezetimibe
Inhibit cholesterol Reduce cholesterol
production  absorption

Bempedoic
acid ???
Bile acid
Niacin
sequestrants
in high doses
Make liver converts
increase HDL
more cholesterol into 5
cholesterol
bile acids
 Bempedoic acid

Bempedoic acid is a novel non-statin drug that

inhibits cholesterol biosynthesis in the same
pathway as statins.

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 Approval status

 Bempedoic acid was approved by FDA in February 2020 as an adjunct to diet

and maximally tolerated statin therapy for the treatment of adults with
heterozygous familiar hypercholesterolemia or established atherosclerotic
cardiovascular disease who require additional lowering of LDL-C.

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 Availability

Oral dosage form of 180 mg (branded as

NEXLETOL™)

A fixed-dose combination of Bempedoic

acid and ezetimibe (branded as
NEXLIZET™)

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 Mechanism of action

Bempedoic acid
inhibit the cholesterol
synthesis by
inhibiting ATP-citrate
lyase (ACL)

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 Adverse effects

• Hyperuricemia and gout symptoms • Bronchitis,

• A slightly increased risk of tendon
rupture
• Upper respiratory tract infection,
• Back pain,
• Abdominal pain or discomfort,
• Pain in extremity,
• Anemia,
• Elevated liver enzymes

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 Advantage over statin

Bempedoic acid is not associated with muscular disorder as

statin ( lack of active metabolites in skeletal muscles)

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Examples of
Clinical
Trials on
Bempedoic
Acid

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Clinical trials

Conclusion :
Bempedoic acid added to
maximally tolerated
statin therapy did not lead
to a higher incidence of
overall adverse events than
placebo and led to
significantly lower LDL
cholesterol levels

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Clinical trials

Conclusion:
Bempedoic acid
offers a safe and
effective oral
therapeutic option
for lipid lowering
in patients who
cannot tolerate
statins
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Clinical trials

Conclusion:
Bempedoic acid seems
to have unfavorable
effects on serum uric
acid, creatinine level
and the incidence of
gout

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Clinical trials

Conclusions:
The Bempedoic acid and
ezetimibe fixed-dose
combination significantly
lowered LDL-cholesterol
versus placebo or other
oral monotherapies 
This combination had
favorable safety profile

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 CLEAR cardiovascular outcomes trial

• Is a phase 3, event-driven, randomized, multicenter, double-

blind, placebo-controlled trial
• Designed to evaluate whether treatment with Bempedoic acid
reduces the risk of cardiovascular events.

Actual Study Start November 18, 2016

Date  :
Estimated Study December 2022 17
Completion Date  :
 Conclusion

• Bempedoic acid is a novel class of non-statin therapy that targets hepatic

cholesterol

• It demonstrated significant LDL-c lowering ability as monotherapy and

in combination with ezetimibe

• If long term safety are favorable, Bempedoic acid will improve

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cardiovascular risk prevention in statin-intolerant patients
 References

1. Ibrahim MA, Asuka E, Jialal I. Hypercholesterolemia. [Updated 2020 Aug 30]. In: Statpearls [Internet]. Treasure
Island (FL): Statpearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/nbk459188/
2. Mandal A. 2019. Hypercholesterolemia Treatment. News-medical, Accessed 26 October 2020. Available from:
https://www.news-medical.net/health/hypercholesterolemia-treatment.aspx
3. Ogbru O and  Marks JW. 2019. Bile Acid Sequestrants. Medicine Net, Accessed 26 October 2020. Available from:
https://www.medicinenet.com/bile_acid_sequestrants/article.htm#how_do_bile_acid_sequestrants_work
4. Tibuakuu M ,  Blumenthal RS,  Martin SS. 2020. Bempedoic Acid For LDL-C Lowering: What Do We Know?
Accessed 25 October 2020. Available from: https://www.acc.org/latest-in-
cardiology/articles/2020/08/10/08/21/bempedoic-acid-for-ldl-c-lowering
5. Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic Acid Plus Ezetimibe Fixed-dose Combination In Patients
With Hypercholesterolemia And High CVD Risk Treated With Maximally Tolerated Statin Therapy. Eur J Prev
Cardiol. 2020 Apr;27(6):593-603. Doi: 10.1177/2047487319864671. 
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